# Soft tissue tumours **DR LALIMA TIWARI** BDSC (UWA), DCLINDENT (ORALMED) (UWA), MRACDS (ORALMED), FOMAA ORAL MEDICINE SPECIALIST CLINICAL SENIOR LECTURER #### Clinical Leadership and Expertise Presented by Dr. Lalima Tiwari, an Oral Medicine Specialist and Clinical Senior Lecturer. **Professional Qualifications:** - BDSC (UWA) - DClinDent (OralMed) (UWA) - MRACDS (OralMed) - FOMAA # Learning Outcomes Knowledge of soft tissue (mesenchymal) tumours including developmental, reactive and neoplastic lesions. 1. Describe the aetiology, pathogenesis, the clinical and histopathologic features and the diagnosis and treatment of the following developmental and reactive lesions: - Vascular malformations - Fibro-epithelial polyps - Fibrous epulides - Denture hyperplasia - Inflammatory papillary hyperplasia - Pyogenic granuloma This section provides comprehensive knowledge of soft tissue (mesenchymal) tumours, encompassing developmental, reactive, and neoplastic lesions. #### Clinical Competencies for Developmental and Reactive Lesions Students should be able to describe the aetiology, pathogenesis, clinical and histopathologic features, diagnosis, and treatment of the following conditions: 1. Vascular malformations 2. Fibro-epithelial polyps 3. Fibrous epulides 4. Denture hyperplasia 5. Inflammatory papillary hyperplasia 6. Pyogenic granuloma # Mesenchymal tumours Tumours originating from mesodermal-derived precursor cells - Bone - Cartilage - Blood vessels - Adipose tissue - Smooth muscle - Fibroblasts Mesenchymal tumours originate from precursor cells derived from the mesoderm. These tumours can arise from various connective and supportive tissues, including: - Bone - Cartilage - Blood vessels - Adipose tissue - Smooth muscle - Fibroblasts # Vascular malformations ## Clinical Features - Wide range age manifestations - 4-10% of newborn children: congenital lesions – labelled birthmarks - Clinical features vary according to extension of lesion, location and displacement of neighbouring tissue - Port wine stain most common vascular malformation - Skin, oral mucosa, sclera - Isolated or part of systemic disease - Slow-flow vascular malformation detected at birth - Vary in colour depending on depth: normal colour – deep purple - Consider haemangioma → continuous growth ### High flow vascular malformations - 3rd decade of life - Bluish- colour - Arteriovenous malformation (AVM) – swelling, pain, bleeding, not fluctuant, pulsatile ### Mixed - Behave as high flow due to arterial supply - Should be distinguished from HHT ### Intraosseous - Poorly defined borders or well – circumscribed halo - unilocular, multilocular - Unicystic to honeycomb appearance - Bone expansion Vascular malformations present with a wide range of age manifestations, with 4-10% of newborn children presenting with congenital lesions often labeled as birthmarks. Clinical features vary according to the extension of the lesion, its location, and the displacement of neighboring tissue. #### Capillary and Slow-Flow Malformations - **Port wine stain:** The most common vascular malformation. It can affect the skin, oral mucosa, and sclera, appearing either in isolation or as part of a systemic disease. - **Slow-flow malformations:** Typically detected at birth. - Color varies depending on depth, ranging from normal skin color to deep purple. - Must be distinguished from haemangioma, which exhibits continuous growth. #### High-Flow Vascular Malformations - Often manifest in the 3rd decade of life. - Typically present with a bluish color. - **Arteriovenous malformation (AVM):** Characterized by swelling, pain, and bleeding. These are pulsatile and not fluctuant. #### Mixed and Intraosseous Presentations - **Mixed lesions:** Behave as high-flow due to arterial supply; should be distinguished from Hereditary Hemorrhagic Telangiectasia (HHT). - **Intraosseous lesions:** Present with poorly defined borders or well-circumscribed halos. - Radiographic appearance ranges from unilocular or multilocular to unicystic or honeycomb patterns. - May cause bone expansion. ```markdown Most common vascular malformations of the head and neck according to blood flow pattern | Slow flow | High flow | |---|---| | Sturge-Weber syndrome | Arteriovenous malformations | | Venous malformations | Arteriovenous fistula | | Capillary malformations | Capillary arteriovenous malformation | | Capillary venous malformation | Capillary lymphatic venous arteriovenous malformation | | Capillary lymphatic malformation | | | Lymphatic venous malformation | | | Capillary lymphatic venous malformation | | ```  tumours_slides_figures/img_354f13b9db7a2e3e.webp) The following table categorizes the most common vascular malformations of the head and neck based on their blood flow characteristics: | Slow Flow | High Flow | | :--- | :--- | | Sturge-Weber syndrome | Arteriovenous malformations | | Venous malformations | Arteriovenous fistula | | Capillary malformations | Capillary arteriovenous malformation | | Capillary venous malformation | Capillary lymphatic venous arteriovenous malformation | | Capillary lymphatic malformation | | | Lymphatic venous malformation | | | Capillary lymphatic venous malformation | | A table categorizing the most common vascular malformations of the head and neck according to blood flow pattern, divided into 'Slow flow' and 'High flow' categories. The 'Slow flow' column lists conditions such as Sturge-Weber syndrome, venous malformations, and capillary malformations, while the 'High flow' column includes arteriovenous malformations, arteriovenous fistula, and capillary arteriovenous malformation. # Histopathology of Capillary Malformation Capillary malformation (CM). (A) Facial CM with lip hypertrophy in a 4-year-old boy showing an excessive number of thin-walled venule-like channels with narrow lumens (hematoxylin-eosin, original magnification ×100). (B) Facial CM with lip hypertrophy in a 17-year-old boy has an increased number of enlarged vein-like channels with both thin and thick, mostly fibrous walls. Intervascular fibrous tissue is increased (hematoxylin-eosin, original magnification ×100). (C) Facial CM with thickening and nodules in a 35-year-old man with Sturge-Weber syndrome. Nasal skin shows a nodular cluster of large, abnormal vein-like channels. Fibrosis and follicular dilatation and keratin plugging are present (hematoxylin-eosin, original magnification ×40). --- Anita Gupta MD and Harry Kozakewich MD Clinics in Plastic Surgery, 2011-01-01, Volume 38, Issue 1, Pages 31-44, Copyright © 2011  tumours_slides_figures/img_ca12469658501000.webp)  tumours_slides_figures/img_642ab3d488d47cad.webp) #### Capillary Malformation (CM) Histology - **Facial CM with lip hypertrophy (4-year-old):** Shows an excessive number of thin-walled venule-like channels with narrow lumens. - **Facial CM with lip hypertrophy (17-year-old):** Characterized by an increased number of enlarged vein-like channels with both thin and thick, mostly fibrous walls. There is an increase in intervascular fibrous tissue. - **Facial CM in Sturge-Weber syndrome (35-year-old):** Nasal skin shows a nodular cluster of large, abnormal vein-like channels. Histology reveals fibrosis, follicular dilatation, and keratin plugging. Microscopic images of capillary malformation (CM) showing different cases: (A) a 4-year-old boy with facial CM and lip hypertrophy displaying numerous thin-walled venule-like channels with narrow lumens; (B) a 17-year-old boy with facial CM and lip hypertrophy showing enlarged vein-like channels with thin and thick fibrous walls and increased intervascular fibrous tissue. Both are stained with hematoxylin-eosin at ×100 magnification. Microscopic image of a facial CM with thickening and nodules in a 35-year-old man with Sturge-Weber syndrome, showing a nodular cluster of large, abnormal vein-like channels with fibrosis and follicular dilatation and keratin plugging. The image is stained with hematoxylin-eosin at ×40 magnification. # Histopathology of venous malformations Venous (VM) and glomuvenous malformation (GVM). (A) VM shows malformed venous channels with an organizing thrombus (hematoxylin-eosin, original magnification ×20). (B) Venous wall is irregularly muscularized and focally lacks muscle (hematoxylin-eosin, original magnification ×100). (C) GVM overview of a deep dermal/subcutaneous lesion with organizing thrombi (hematoxylin-eosin, original magnification ×20). (D) Vascular channels in GVM have cuboidal glomus cells replacing smooth muscle (hematoxylin-eosin, original magnification ×200). (E) Glomus cells are highlighted by smooth muscle actin immunostain (original magnification ×200). --- Anita Gupta MD and Harry Kozakewich MD Clinics in Plastic Surgery, 2011-01-01, Volume 38, Issue 1, Pages 31-44, Copyright © 2011  tumours_slides_figures/img_12c647abd0a13742.webp) #### Venous (VM) and Glomuvenous Malformation (GVM) Histology - **Venous Malformation (VM):** Exhibits malformed venous channels often containing organizing thrombi. The venous walls are irregularly muscularized and may focally lack muscle. - **Glomuvenous Malformation (GVM):** - Deep dermal/subcutaneous lesions often present with organizing thrombi. - Vascular channels feature cuboidal glomus cells that replace the standard smooth muscle. - Glomus cells can be specifically highlighted using smooth muscle actin immunostaining. Five histopathological images (A-E) showing venous malformations and glomuvenous malformations. Image (A) displays malformed venous channels with an organizing thrombus at ×20 magnification. Image (B) shows an irregularly muscularized venous wall lacking muscle at ×100 magnification. Image (C) presents a GVM overview of a deep dermal/subcutaneous lesion with organizing thrombi at ×20 magnification. Image (D) illustrates vascular channels in GVM with cuboidal glomus cells replacing smooth muscle at ×200 magnification. Image (E) highlights glomus cells using smooth muscle actin immunostain at ×200 magnification. # Histopathology of lymphatic malformations Lymphatic malformation (LM). (A) Macrocystic lymphatic malformation (cyst-like channels are greater or equal to 1 cm. (B) Microcystic LM showing vascular channels less than 1 cm (hematoxylin-eosin, original magnification ×2). (C) These small thin-walled channels in LM have thin endothelial cells with no apparent muscular wall and lumens contain protein and lymphocytes (hematoxylin-eosin, original magnification ×20). (D) lymphatic endothelium is highlighted by PROX-1, brown nuclear stain (PROX-1 immunostain, original magnification ×10) and (E) D240, brown cytoplasmic stain (D240 immunostain, original magnification ×20). --- Anita Gupta MD and Harry Kozakewich MD Clinics in Plastic Surgery, 2011-01-01, Volume 38, Issue 1, Pages 31-44, Copyright © 2011  tumours_slides_figures/img_004d6a401ec30731.webp) #### Lymphatic Malformation (LM) Histology - **Macrocystic LM:** Characterized by cyst-like channels measuring 1 cm or greater. - **Microcystic LM:** Features vascular channels less than 1 cm in size. - **Channel Characteristics:** Small, thin-walled channels in LM possess thin endothelial cells without an apparent muscular wall. Lumens typically contain protein and lymphocytes. - **Immunohistochemistry:** - **PROX-1:** Highlights lymphatic endothelium with a brown nuclear stain. - **D240:** Highlights lymphatic endothelium with a brown cytoplasmic stain. The image displays a composite figure with five panels (A-E) showing histopathological features of lymphatic malformations. Panel A shows a macrocystic lymphatic malformation with large cyst-like channels, while panel B illustrates microcystic LM with smaller vascular channels. Panels C, D, and E provide detailed views of thin-walled channels, PROX-1 immunostain highlighting lymphatic endothelium, and D240 immunostain showing cytoplasmic staining, respectively. # Histopathology of AVM Arteriovenous malformation (AVM) and PTEN hamartoma of soft tissue (PHOST). (A) AVM shows malformed arteries and veins (hematoxylin-eosin, original magnification ×20). (B) AVM with Verhoeff-van Gieson stain highlights the disrupted internal elastic lamina in arteries with transition to indeterminate type elastic pattern (top vessel; VVG special stain, original magnification ×4). (C) Small vessel (proliferative component) in AVM has foci of small channels with plump endothelium and pericytes (hematoxylin-eosin, original magnification ×400). (D) Intramuscular PHOST shows a large nodule composed of a large vein (long arrow) with a very irregular lumen and focally hypermuscularized wall surrounded by prominent arteries (shorter arrow) and dense fibrous tissue containing small myxoid vascular nodules and (shortest arrow) and lymphoid clusters (horizontal arrow) (hematoxylin-eosin, original magnification ×40). (E) PHOST with tortuous arteries showing transmural muscular hyperplasia and small lumens (hematoxylin-eosin, original magnification ×100). (F) Some vascular clusters in PHOST are composed of very thin-walled abnormal veins resembling pulmonary alveoli (hematoxylin-eosin, original magnification ×100). --- Anita Gupta MD and Harry Kozakewich MD Clinics in Plastic Surgery, 2011-01-01, Volume 38, Issue 1, Pages 31-44, Copyright © 2011  tumours_slides_figures/img_464c1e41e4250f73.webp) #### Arteriovenous Malformation (AVM) and PTEN Hamartoma (PHOST) Histology - **Arteriovenous Malformation (AVM):** - Shows malformed arteries and veins. - Verhoeff-van Gieson (VVG) stain highlights a disrupted internal elastic lamina in arteries with a transition to an indeterminate elastic pattern. - Proliferative components may show small channels with plump endothelium and pericytes. - **PTEN Hamartoma of Soft Tissue (PHOST):** - **Intramuscular PHOST:** Features large nodules composed of large veins with irregular lumens and focally hypermuscularized walls, surrounded by prominent arteries. - **Tissue Composition:** Contains dense fibrous tissue, small myxoid vascular nodules, and lymphoid clusters. - **Vascular Clusters:** Some clusters are composed of very thin-walled abnormal veins resembling pulmonary alveoli; tortuous arteries may show transmural muscular hyperplasia and small lumens. Six histopathological images (A-F) showing various features of arteriovenous malformation (AVM) and PTEN hamartoma of soft tissue (PHOST). Images include malformed arteries and veins, disrupted elastic lamina, proliferative small vessels, intramuscular nodules with irregular veins and arteries, tortuous arteries with muscular hyperplasia, and thin-walled abnormal veins resembling pulmonary alveoli, all stained with hematoxylin-eosin or Verhoeff-van Gieson. ```html <table> <tr> <td><img src="https://i.imgur.com/1.png" alt="Clinical image a" /></td> <td><img src="https://i.imgur.com/2.png" alt="Clinical image b" /></td> </tr> <tr> <td><img src="https://i.imgur.com/3.png" alt="Clinical image c" /></td> <td><img src="https://i.imgur.com/4.png" alt="Clinical image d" /></td> </tr> </table> Vascular malformation at the apex of the tongue presenting clinically as a red patch (a). Diascopy (blanching procedure) reveals whitish appearance after compression (b). Low power magnification of venous-capillary malformation showing multiple blood vessels of variable width (c + d) (Hematoxylin and eosin stain) Clinical images from Contemporary Oral Medicine ```  tumours_slides_figures/img_bf6dbc4ec90f2ba7.webp)  tumours_slides_figures/img_9ea9e25c1fe08d1d.webp)  tumours_slides_figures/img_7f22f28841626ca5.webp)  tumours_slides_figures/img_e75e64a966535972.webp)  tumours_slides_figures/img_743c34fc530920d9.webp) #### Clinical and Microscopic Presentation: Tongue Apex - **Clinical Presentation:** A vascular malformation at the apex of the tongue appearing as a red patch. - **Diagnostic Procedure:** Diascopy (blanching procedure) reveals a whitish appearance upon compression, confirming the vascular nature. - **Microscopic Findings:** Low power magnification of a venous-capillary malformation reveals multiple blood vessels of variable width. A composite figure showing four images of a vascular malformation at the apex of the tongue. Image (a) is a clinical photo of a red patch, (b) shows the whitish appearance after diascopy, and (c) and (d) are histological photos of venous-capillary malformation with multiple blood vessels of variable width under low power magnification. Clinical photo of a vascular malformation at the apex of the tongue, appearing as a red patch. Clinical photo showing the whitish appearance of the vascular malformation after diascopy (blanching procedure). Histological photo of a venous-capillary malformation at low power magnification, showing multiple blood vessels of variable width. Histological photo of a venous-capillary malformation at low power magnification, showing multiple blood vessels of variable width. # Vascular malformations ## Diagnosis - Diagnosis is important to determine appropriate treatment planning - Microscopic evaluation provides best impression of the vascular alterations present in the lesion – sometimes high risk for patient - Differentiate from haemangioma - Nerve bundles consistently present in vascular malformations - Hyper contrast CT examination - MRI is best imaging tool for diagnosis and treatment planning - Magnetic resonance arteriogram and a computed tomograph arteriogram can give excellent images of AVM Accurate diagnosis is essential for appropriate treatment planning. #### Diagnostic Modalities - **Microscopic Evaluation:** Provides the most detailed impression of vascular alterations. It is critical for differentiating malformations from haemangiomas. A key histological marker is the consistent presence of nerve bundles within vascular malformations. - **Imaging Tools:** - **MRI:** Considered the best imaging tool for both diagnosis and treatment planning. - **Arteriography:** Magnetic resonance arteriograms (MRA) and computed tomograph arteriograms (CTA) provide excellent visualization of Arteriovenous Malformations (AVM). - **Hyper-contrast CT:** Utilized for further examination of the lesion's extent. ```markdown AVM High-flow arteriovenous malformation. The patient presents with a pinkish non-fluctuating nodule extending from the midline of the lower lip to the left labial commissure (a + b). The mucosal aspect of the lesion (c) and clinical compression exam (d) reveals the pulsating behavior of the lesion indicating its flow pattern. MRA exam reveals the arterial origin from the facial artery and the appearance of an arteriovenous fistula forming a plexiform arrangement with dilated vessels and the effluent mental vein (e–g). Microscopic aspect of the arteriovenous malformation (h), revealing the close relationship of arteries with thick walls and narrow lumen, and veins with dilated blood-filled lumen and thin vascular walls. The lesion infiltrates the surrounding tissue. In this specimen, adipose tissue is seen with striated skeletal muscle as well as neural fibers in the original connective tissue from the affected area (Hematoxylin and eosin stain) Clinical images from Contemporary Oral Medicine ``` #### High-Flow Arteriovenous Malformation Case Study - **Clinical Presentation:** A pinkish, non-fluctuating nodule extending from the midline of the lower lip to the labial commissure. - **Clinical Examination:** Compression reveals pulsating behavior, indicating a high-flow pattern. - **Imaging (MRA):** Reveals an arterial origin from the facial artery and an arteriovenous fistula forming a plexiform arrangement with dilated vessels and an effluent mental vein. - **Microscopic Aspect:** - Demonstrates a close relationship between thick-walled arteries with narrow lumens and thin-walled veins with dilated, blood-filled lumens. - The lesion infiltrates surrounding tissues, including adipose tissue, striated skeletal muscle, and neural fibers. # Vascular malformations ## Treatment - Usually need treatment at multi-disciplinary centre - Conservative measures - Only effective for venous malformations - Electrocautery - Laser therapy - Embolotherapy combined with surgical excision - AVM Management of vascular malformations usually requires a multi-disciplinary center approach. #### Treatment Modalities - **Conservative Measures:** Generally only effective for venous malformations. - **Electrocautery:** Used for targeted tissue destruction. - **Laser Therapy:** Utilized for superficial or specific vascular components. - **Combined Therapy:** Embolotherapy combined with surgical excision is frequently required, particularly for Arteriovenous Malformations (AVM). # Fibroepithelial polyp - Fibrous nodule - **Aetiolog**y: Induced by recurrent local irritants of oral cavity – bite trauma, denture irritation, food impaction, poor oral hygiene - **Pathophysiology**: Reactive proliferation rather than true neoplasm ## Clinical Features - Smooth, round, exophytic nodule - Pedunculated or sessile with normal overlying epithelium - Can be ulcerated, or demonstrate thickened white surface (hyperkeratosis) - Asymptomatic generally - 1-2 cm in diameter - Labial mucosa, tongue, palate <img src="https://i.imgur.com/5zJZvzr.jpg" alt="Image of fibroepithelial polyp in oral cavity"> Smith MH. Irritation fibroma. PathologyOutlines.com  tumours_slides_figures/img_649c94f221470567.webp) - Fibrous nodule - **Aetiology**: Induced by recurrent local irritants of oral cavity – bite trauma, denture irritation, food impaction, poor oral hygiene - **Pathophysiology**: Reactive proliferation rather than true neoplasm #### Clinical Features - Smooth, round, exophytic nodule - Pedunculated or sessile with normal overlying epithelium - Can be ulcerated, or demonstrate thickened white surface (hyperkeratosis) - Asymptomatic generally - 1-2 cm in diameter - Labial mucosa, tongue, palate A clinical photograph showing a fibroepithelial polyp in the oral cavity, appearing as a smooth, round, exophytic nodule on the labial mucosa. The lesion is pedunculated with normal overlying epithelium and is being held by a gloved hand, illustrating its size and location. # Fibroepithelial polyp ## Histopathology - Nonencapsulated nodular mass - Mass composed of fibrous connective tissue with collagen bundles interspersed with fibroblasts, blood vessels and scattered chronic inflammatory cells - Overlying surface of squamous epithelium ## Diagnosis - Definitive diagnosis made upon histopathological examination - Highly suspected based on clinical features ## Treatment - Surgical excision with removal of local irritants <img src="https://i.imgur.com/8JZJzJl.png" alt="Microscopic image of fibroepithelial polyp tissue section stained with H&E, showing a nodular mass with a surface layer of squamous epithelium and underlying fibrous connective tissue with collagen bundles, fibroblasts, blood vessels, and chronic inflammatory cells." /> Smith MH. Irritation fibroma. PathologyOutlines.com  tumours_slides_figures/img_739b14364e915362.webp) #### Histopathology - Nonencapsulated nodular mass - Mass composed of fibrous connective tissue with collagen bundles interspersed with fibroblasts, blood vessels and scattered chronic inflammatory cells - Overlying surface of squamous epithelium #### Diagnosis - Definitive diagnosis made upon histopathological examination - Highly suspected based on clinical features #### Treatment - Surgical excision with removal of local irritants Microscopic image of a fibroepithelial polyp tissue section stained with H&E, showing a nodular mass with a surface layer of squamous epithelium and underlying fibrous connective tissue containing collagen bundles, fibroblasts, blood vessels, and chronic inflammatory cells, consistent with the histopathological description provided. ```markdown # Fibrous epulides Fibrous lump on the gingiva Localised hyperplastic fibrous gingival mass formed as a response to chronic irritation ## Clinical features: - Smooth pink nodule on marginal/attached gingiva - Often around inflamed gingiva ## Histopathological features: - Mature fibrous tissue - Minimal inflammation - Mineralisation commonly seen – dystrophic calcification ## Diagnosis - Histopathological evaluation needed to confirm diagnosis ## Treatment - Surgical excision to periosteum, scale and clean, with removal of local irritants - Recurrence can occur if irritants not removed <img src="https://i.imgur.com/7ZjKz9l.png" alt="Histopathological image of fibrous epulide"/> <img src="https://i.imgur.com/7ZjKz9l.png" alt="Clinical image of fibrous epulide"/> Clinical images from Contemporary Oral Medicine ```  tumours_slides_figures/img_946edc4e1a115cbc.webp)  tumours_slides_figures/img_af0bb61e99063fac.webp) Fibrous lump on the gingiva representing a localised hyperplastic fibrous gingival mass formed as a response to chronic irritation. #### Clinical Presentation - Smooth pink nodule on marginal/attached gingiva - Often around inflamed gingiva #### Histopathological Features - Mature fibrous tissue - Minimal inflammation - Mineralisation commonly seen – dystrophic calcification #### Diagnosis and Management - Histopathological evaluation needed to confirm diagnosis - Surgical excision to periosteum, scale and clean, with removal of local irritants - Recurrence can occur if irritants not removed Histopathological image of a fibrous epulide showing mature fibrous tissue with dystrophic calcification, stained with hematoxylin and eosin, illustrating the microscopic features of the lesion. Clinical image of a fibrous epulide, displaying a smooth pink nodule on the marginal gingiva, consistent with a localized hyperplastic fibrous mass often associated with chronic irritation. ```markdown # Denture hyperplasia - Denture fibroma - Flabby ridge - Inflammatory hyperplastic reaction by chronic irritation, usually due to ill-fitting dentures ## Clinical features: - Sessile or pedunculated, pink nodules - Slow growing - On alveolar ridges or denture bearing areas, usually seen under dentures ## Histopathology: - Epithelial hyperplasia, acanthosis, pseudo-epitheliomatous hyperplasia ## Diagnosis - Based on clinical features and histopathological assessment ## Treatment: - Local surgical excision - New, well-fitting dentures - Denture hygiene <img src="https://i.imgur.com/5QjZqXl.jpg" alt="Clinical image of denture hyperplasia"> <img src="https://i.imgur.com/5QjZqXl.jpg" alt="Clinical image of denture hyperplasia"> Clinical images from Contemporary Oral Medicine ```  tumours_slides_figures/img_32fc4cacd4fe5b91.webp)  tumours_slides_figures/img_88f3ab2b1e7c9b9c.webp) Also known as denture fibroma or flabby ridge, this is an inflammatory hyperplastic reaction caused by chronic irritation, usually due to ill-fitting dentures. #### Clinical Features - Sessile or pedunculated, pink nodules - Slow growing - Located on alveolar ridges or denture bearing areas, usually seen under dentures #### Histopathology - Epithelial hyperplasia, acanthosis, pseudo-epitheliomatous hyperplasia #### Diagnosis - Based on clinical features and histopathological assessment #### Management - Local surgical excision - New, well-fitting dentures - Denture hygiene Clinical photograph showing a pink, sessile or pedunculated nodule on the alveolar ridge, consistent with denture hyperplasia, with a gloved hand retracting the tissue for better visualization. Clinical photograph depicting a surgical procedure on a hyperplastic lesion in the oral cavity, with a surgical instrument grasping the tissue, illustrating the treatment of denture hyperplasia. # Inflammatory papillary hyperplasia - Benign soft tissue lesion - Often associated with use of removable upper dentures; pathogenesis unclear - **Aetiology**: Ill-fitting dentures, continuous day and night denture use, poor oral hygiene, sensitivity to denture liners, tobacco - Often associated with colonization of Candida caused by poor oral hygiene - **Clinical features**: - Growth of one or more nodular lesions - 2mm or less - Almost exclusively involves the hard palate - Mostly asymptomatic - Colour of mucosa may vary from pink to red <img src="https://i.imgur.com/1X7z8Jt.jpg" alt="Image showing oral lesions and dentures"/> Gual-Vaqués P, Jané-Salas E, Egido-Moreno S, Ayuso-Montero R, Mari-Roig A, López-López J. Inflammatory papillary hyperplasia: A systematic review. Med Oral Patol Oral Cir Bucal. 2017 Jan 1;22(1):e36-e42. doi: 10.4317/medoral.21405. PMID: 27918740; PMCID: PMC5217495.  tumours_slides_figures/img_5a4e73ca849cc4bd.webp) Benign soft tissue lesion often associated with use of removable upper dentures; pathogenesis is unclear. #### Aetiology - Ill-fitting dentures, continuous day and night denture use, poor oral hygiene, sensitivity to denture liners, tobacco - Often associated with colonization of Candida caused by poor oral hygiene #### Clinical Features - Growth of one or more nodular lesions - 2mm or less in size - Almost exclusively involves the hard palate - Mostly asymptomatic - Colour of mucosa may vary from pink to red A clinical photograph showing inflammatory papillary hyperplasia on the hard palate, with white arrows pointing to the nodular lesions. The image also includes a small inset of a removable denture, illustrating the association between the condition and denture use. # Inflammatory papillary hyperplasia ## Histopathology: - Papillary projections covered by stratified squamous epithelium with or without chronic inflammation ## Diagnosis: - Clinical examination and histopathological evaluation ## Treatment: - Depends on severity - Laser - Electrosurgery - Cryotherapy - Small localised lesions: 0.12% chlorhexidine mouthrinse, antifungal gels, local excision <img src="https://i.imgur.com/5KQzX8L.png" alt="Histological image of inflammatory papillary hyperplasia showing papillary projections covered by stratified squamous epithelium." /> Gual-Vaqués P, Jané-Salas E, Egido-Moreno S, Ayuso-Montero R, Mari-Roig A, López-López J. Inflammatory papillary hyperplasia: A systematic review. Med Oral Patol Oral Cir Bucal. 2017 Jan 1;22(1):e36-e42. doi: 10.4317/medoral.21405. PMID: 27918740; PMCID: PMC5217495.  tumours_slides_figures/img_682eb03b19cfcf5e.webp) #### Histopathology - Papillary projections covered by stratified squamous epithelium with or without chronic inflammation #### Diagnosis - Clinical examination and histopathological evaluation #### Treatment Treatment depends on severity and may include: - Laser - Electrosurgery - Cryotherapy - Small localised lesions: 0.12% chlorhexidine mouthrinse, antifungal gels, local excision Histological image showing papillary projections covered by stratified squamous epithelium, consistent with inflammatory papillary hyperplasia. The image displays characteristic features including epithelial proliferation and underlying chronic inflammation, as described in the accompanying text. # Pyogenic granuloma - Benign soft tissue lesion ## Aetiology - History of trauma - Response of tissues to minor trauma and/or chronic irritation - Associated with poor oral hygiene, chronic trauma, pregnancy, medications ## Pathogenesis - Largely unknown, although in pregnancy, estrogen enhances vascular endothelial growth factor (VEGF) production in macrophages, likely contributing to the development of pyogenic granulomas - Also in pregnancy, progesterone may function as an immunosuppressant in gingiva, preventing an acute inflammatory reaction against oral bacteria and resulting in proliferative gingival inflammation - Increased estrogen and progesterone in pregnancy increases concentrations of *Prevotella intermedia* in the subgingival biofilm, decreases the host response to the bacteria and increases the vascular permeability and infiltration of fluids into the gingival tissues, contributing to formation of pyogenic granulomas Kamal R, Dahiya P, Puri A. Oral pyogenic granuloma: Various concepts of etiopathogenesis. J Oral Maxillofac Pathol. 2012;16(1):79-82. doi:10.4103/0973-029X.92978 Benign soft tissue lesion. #### Aetiology - History of trauma - Response of tissues to minor trauma and/or chronic irritation - Associated with poor oral hygiene, chronic trauma, pregnancy, medications #### Pathogenesis - Largely unknown, although in pregnancy, estrogen enhances vascular endothelial growth factor (VEGF) production in macrophages, likely contributing to development. - Progesterone in pregnancy may function as an immunosuppressant in gingiva, preventing an acute inflammatory reaction against oral bacteria and resulting in proliferative gingival inflammation. - Increased estrogen and progesterone in pregnancy increases concentrations of *Prevotella intermedia* in the subgingival biofilm, decreases the host response, and increases vascular permeability and fluid infiltration. # Pyogenic granuloma ## Clinical features - Wide range of ages affected - Gingiva most common site - Can occur extra orally - Soft, painless, deep red to reddish-purple in colour ## Histopathology: - Highly vascularized proliferation of granulation tissue - Often demonstrates surface ulceration and a subacute inflammatory cell infiltrate comprised of neutrophils, lymphocytes and plasma cells - May demonstrate a lobular arrangement of capillary vessels and proliferating endothelial cells delineated by fibrous septae (termed lobular capillary hemangioma) - May be pedunculated - May show brisk mitotic rate (up to 10 mitotic figures per high power field); however, lacks pleomorphism <img src="https://i.imgur.com/1VZQz8E.jpg" alt="Clinical image of pyogenic granuloma on gingiva"/> <img src="https://i.imgur.com/9WzZz8E.jpg" alt="Histopathological slide of pyogenic granuloma"/> Kamal R, Dahiya P, Puri A. Oral pyogenic granuloma: Various concepts of etiopathogenesis. J Oral Maxillofac Pathol. 2012;16(1):79-82. doi:10.4103/0973-029X.92978 Smith MH. Pyogenic granuloma. PathologyOutlines.com website. h  tumours_slides_figures/img_f8f8a3109ee79e4a.webp)  tumours_slides_figures/img_694818e661a18b44.webp) #### Clinical Features - Wide range of ages affected - Gingiva most common site; can occur extra orally - Soft, painless, deep red to reddish-purple in colour #### Histopathology - Highly vascularized proliferation of granulation tissue - Often demonstrates surface ulceration and a subacute inflammatory cell infiltrate comprised of neutrophils, lymphocytes and plasma cells - May demonstrate a lobular arrangement of capillary vessels and proliferating endothelial cells delineated by fibrous septae (termed lobular capillary hemangioma) - May be pedunculated - May show brisk mitotic rate (up to 10 mitotic figures per high power field); however, lacks pleomorphism Clinical image of a pyogenic granuloma on the gingiva, showing a soft, painless, deep red to reddish-purple lesion located between the teeth. Histopathological slide of a pyogenic granuloma, displaying a highly vascularized proliferation of granulation tissue with a lobular arrangement of capillary vessels and proliferating endothelial cells. # Pyogenic granuloma ## Differential diagnosis: - Peripheral giant cell granuloma - Peripheral ossifying fibroma - Fibroma - Peripheral odontogenic fibroma - Haemangioma - Kaposi’s sarcoma ## Diagnosis - Diagnosis made on histopathological evaluation ## Treatment - Surgical excision of gingival lesions - curettage of underlying tissue - Remove causative agent - Recurrence rate of 15.8% #### Differential Diagnosis - Peripheral giant cell granuloma - Peripheral ossifying fibroma - Fibroma - Peripheral odontogenic fibroma - Haemangioma - Kaposi’s sarcoma #### Diagnosis - Diagnosis made on histopathological evaluation #### Treatment - Surgical excision of gingival lesions - Curettage of underlying tissue - Remove causative agent - Recurrence rate of 15.8% # Neurofibroma - Benign peripheral nerve sheath tumour composed of variable mixture of Schwann, Perineural-like, and fibroblastic cells as well as with features intermediate between these various cells, contained in collagenous or myxoid matrix - Can occur as solitary lesion or part of generalised syndrome of neurofibromatosis (4-7% display oral manifestations) ## Pathogenesis: Solitary neurofibroma not associated with Neurofibromatosis-1 poorly understood Somatic inactivation of NF-1 gene located on chromosome 17 leads to increased and abnormal production of neurofibromin which leads to activating p21(ras) and p13 Causes cellular proliferation of Schwann cells associated with neurofibroma --- Storlazzi et al. Journal of Cancer. 2005 Neurofibroma is a benign peripheral nerve sheath tumour composed of a variable mixture of Schwann, perineural-like, and fibroblastic cells. It may also contain cells with features intermediate between these types, all contained within a collagenous or myxoid matrix. - Can occur as a solitary lesion or as part of a generalized syndrome of neurofibromatosis. - Approximately 4-7% of cases display oral manifestations. #### Pathogenesis - The pathogenesis of solitary neurofibromas not associated with Neurofibromatosis-1 (NF-1) is poorly understood. - Somatic inactivation of the NF-1 gene (located on chromosome 17) leads to increased and abnormal production of neurofibromin. - This inactivation leads to the activation of p21(ras) and p13, causing cellular proliferation of Schwann cells associated with neurofibroma. # Neurofibroma ## Clinical features - In the oral cavity present as submucosal, nontender, discrete mass - Intraoral lesions of neural tissues mainly originate from branches of fifth, seventh, rarely ninth cranial nerve - Tongue, buccal mucosa, vestibular area common sites and posterior mandible is the most common intraosseous location - Further divided based on clinical presentation – localised/solitary growth, diffuse discrete, multiple nodules, plexiform types - Overlying mucosa of solitary NF not associated with NF-1 gradually blends with surrounding normal mucosa, no clear-cut demarcation between lesion and normal mucosa <img src="https://i.imgur.com/1Q0jZ0L.jpg" alt="Oral cavity showing submucosal mass"> <img src="https://i.imgur.com/5Q7Z6fJ.jpg" alt="Close-up of solitary neurofibroma on tongue">  tumours_slides_figures/img_6dfdf056bb1d4a38.webp)  tumours_slides_figures/img_673253e906efb43e.webp) #### Clinical Features - In the oral cavity, these present as submucosal, nontender, discrete masses. - Intraoral lesions of neural tissues mainly originate from branches of the fifth, seventh, and rarely the ninth cranial nerves. - Common sites include the tongue, buccal mucosa, and vestibular area. - The posterior mandible is the most common intraosseous location. #### Classification by Presentation Neurofibromas are further divided based on clinical presentation: - Localised/solitary growth - Diffuse discrete - Multiple nodules - Plexiform types In solitary neurofibromas not associated with NF-1, the overlying mucosa gradually blends with surrounding normal mucosa, with no clear-cut demarcation between the lesion and normal tissue. A photo showing a submucosal mass in the oral cavity, illustrating a neurofibroma on the lingual surface near the posterior mandible, consistent with the clinical feature of a discrete, nontender mass. A close-up photo of a solitary neurofibroma on the tongue, highlighting a raised, pinkish nodule with overlying mucosa that blends gradually with surrounding tissue, as described in the text. # Histopathology - Unencapsulated - Proliferation of Schwann cells - Elongated fibroblasts with wavy nuclei separated by abundant collagen fibres - Perineurial cells - Mast cells - Myxoid connective tissue Mahmud A et al. Case Reports Dentistry. 2016 <img src="https://i.imgur.com/4XZjK9L.jpg" alt="Histopathology images (a) to (d)"/> ```html <table> <tr> <td><img src="https://i.imgur.com/4XZjK9L.jpg" alt="Histopathology images (a) to (d)"/></td> </tr> </table> ```  tumours_slides_figures/img_0aa0c5b859037cb3.webp)  tumours_slides_figures/img_73ffeaf9cb2865b0.webp)  tumours_slides_figures/img_95d296425d8aefa6.webp)  tumours_slides_figures/img_fd4f04abe76251a1.webp) #### Histopathology - Unencapsulated lesion. - Proliferation of Schwann cells. - Elongated fibroblasts with wavy nuclei separated by abundant collagen fibres. - Presence of perineurial cells and mast cells. - Myxoid connective tissue component. Histopathology image (a) showing unencapsulated proliferation of Schwann cells with elongated fibroblasts and abundant collagen fibers, stained to highlight cellular structures. Histopathology image (b) displaying elongated fibroblasts with wavy nuclei and abundant collagen fibers, characteristic of the described myxoid connective tissue. Histopathology image (c) illustrating perineurial cells and mast cells within the tissue, with a focus on cellular organization and distribution. Histopathology image (d) showing myxoid connective tissue with scattered cells and a loose extracellular matrix, consistent with the described histopathological features. ```html <table border="1" cellpadding="5" cellspacing="0" style="border-collapse: collapse; width: 100%;"><tr><td style="text-align: center;"><img src="https://i.imgur.com/9ZQZQZQ.png" alt="Figure A: Nasal neurofibroma showing intact squamous mucosa overlying proliferation of Schwann cells, perineurial cells, and fibroblasts blended with collagen fibres." /></td><td style="text-align: center;"><img src="https://i.imgur.com/9ZQZQZQ.png" alt="Figure B: Nasal neurofibroma showing nerve fibre twigs interspersed among Schwann cells, perineurial cells, and collagen fibres; mast cells are also present." /></td></tr></table> <p>Fig. 1.45 Nasal neurofibroma. A An intact squamous mucosa overlies a proliferation of Schwann cells, perineurial cells, and fibroblasts blended with collagen fibres. B Nerve fibre twigs are interspersed among Schwann cells, perineurial cells, and collagen fibres; mast cells are also present.</p> <p><strong>WHO Head and Neck Tumours 2017</strong></p> ```  tumours_slides_figures/img_c429569c00aa1f19.webp) #### Microscopic Observations - **Nasal Neurofibroma:** Features an intact squamous mucosa overlying a proliferation of Schwann cells, perineurial cells, and fibroblasts blended with collagen fibres. - **Cellular Composition:** Nerve fibre twigs are often interspersed among the Schwann cells and perineurial cells; mast cells are typically present within the matrix. Two histological images labeled A and B, showing nasal neurofibroma. Image A displays an intact squamous mucosa overlying a proliferation of Schwann cells, perineurial cells, and fibroblasts blended with collagen fibers. Image B shows nerve fiber twigs interspersed among Schwann cells, perineurial cells, and collagen fibers, with mast cells also present. # Neurofibromatosis type 1 Complex autosomal dominant disorder affecting multiple organ systems Caused by germline mutations in NF1 tumour suppressor gene on chromosome 17 Defining feature of NF-1: neurofibroma Previously known as von Recklinghausen disease Nearly all individuals with NF-1 develop pigmented lesions - Café-au-lait macules - Skinfold freckling - Lisch nodules - Dermal neurofibromas Skeletal abnormalities, brain tumours, peripheral nerve sheath tumours, learning disabilities, social and behavioural problems = lowered QOL Progressive over lifetime, rate of progression and severity vary Gutman D et al. Neurofibromatosis type 1. Nature Reviews Disease Primer. 2017 Neurofibromatosis type 1 (NF-1), previously known as von Recklinghausen disease, is a complex autosomal dominant disorder affecting multiple organ systems. It is caused by germline mutations in the NF1 tumour suppressor gene on chromosome 17. The defining feature of NF-1 is the neurofibroma. #### Clinical Manifestations Nearly all individuals with NF-1 develop pigmented lesions and other systemic features: - Café-au-lait macules - Skinfold freckling - Lisch nodules - Dermal neurofibromas - Skeletal abnormalities - Brain tumours and peripheral nerve sheath tumours - Learning disabilities, social, and behavioural problems resulting in lowered quality of life (QOL) The disease is progressive over a lifetime, though the rate of progression and severity vary between individuals. ```html <table> <tr> <td> <img src="https://i.imgur.com/5JZjKqL.jpg" alt="Typical appearance of multiple Lisch nodules in a patient with neurofibromatosis-1." /> </td> <td> <img src="https://i.imgur.com/5JZjKqL.jpg" alt="Typical appearance of multiple Lisch nodules in a patient with neurofibromatosis-1." /> </td> </tr> </table> ```  tumours_slides_figures/img_22177430a4061d4d.webp)  tumours_slides_figures/img_e3f77c1ebaa86506.webp)  tumours_slides_figures/img_ee37093c1ddcf56c.webp) #### Ocular Findings - **Lisch Nodules:** A typical clinical appearance in patients with neurofibromatosis-1 involves the presence of multiple Lisch nodules in the iris. A photo showing the back of a patient with neurofibromatosis-1, displaying multiple café-au-lait spots and scattered skin lesions. A photo of a child with neurofibromatosis-1, showing multiple café-au-lait spots on the chest and arms against a green background. A close-up photo of an eye showing multiple Lisch nodules, which are characteristic of neurofibromatosis-1, appearing as small, tan-colored bumps on the iris. # NF-1 <img src="https://i.imgur.com/3QZzQzq.png" alt="Three images showing manifestations of NF-1: (a) multiple skin nodules, (b) café-au-lait macules on the arm, (c) MRI showing a spinal lesion marked with an asterisk." /> Gutman D et al. Neurofibromatosis type 1. Nature Reviews Disease Primer. 2017  tumours_slides_figures/img_64e7537314242dac.webp) #### Systemic Involvement Manifestations of NF-1 include: - Multiple skin nodules (dermal neurofibromas). - Café-au-lait macules, often observed on the limbs. - Internal involvement, such as spinal lesions detectable via MRI. Three images showing manifestations of NF-1: (a) multiple skin nodules on a patient's torso, (b) café-au-lait macules on the arm, and (c) an MRI scan showing a spinal lesion marked with an asterisk. # Epidemiology NF-1 Global prevalence: 1 case per 3000 individuals 50% of NF1 cases are familial, remainder arise from de novo NF1 mutation Life expectancy reduced by 8-21 years - Younger individuals – most common cause: malignant peripheral nerve sheath tumour (MPNST) - Cumulative risk of malignancy by 50 years ~ 20-39% - Lifetime cancer risk ~ 60% - 50 fold increased risk for high-grade tumours - Malignant brain tumours - Endocrine cancers - Connective tissue malignancies (1000 fold increased risk for malignant peripheral nerve sheath tumours) - Increased risk of buccal cavity, pharyngeal, oesophageal, skin (melanoma), thyroid, ovarian cancer also described Gutman D et al. Neurofibromatosis type 1. Nature Reviews Disease Primer. 2017 #### Epidemiology and Prognosis - **Global Prevalence:** 1 case per 3,000 individuals. - **Inheritance:** 50% of cases are familial; the remainder arise from de novo NF1 mutations. - **Life Expectancy:** Reduced by 8–21 years. #### Malignancy Risks - The most common cause of death in younger individuals is malignant peripheral nerve sheath tumour (MPNST). - Cumulative risk of malignancy by age 50 is approximately 20–39%. - Lifetime cancer risk is approximately 60%. - There is a 50-fold increased risk for high-grade tumours, including malignant brain tumours and endocrine cancers. - There is a 1000-fold increased risk for MPNSTs. - Increased risks for buccal cavity, pharyngeal, oesophageal, skin (melanoma), thyroid, and ovarian cancers have also been described. # Oral manifestations of NF1 72% of affected individuals exhibit oral manifestations ## Gingival enlargement and pigmentation - Common in children with NF1 - Diffuse, unilateral enlargement of attached gingiva - Fibrous, do not exhibit signs of inflammation - Rare cases: melanin pigmentation of gingiva ## Dental abnormalities - Impacted teeth, supernumerary, missing or displaced teeth - Plexiform neurofibromas can be associated with aplasia of mandibular second molars, increased spacing between teeth and jaw asymmetries ## Neurofibromas - Commonly affect tongue – macroglossia as a result of plexiform neurofibroma ## Osseous lesions of jaw - Not very common – unique for affected individual - May include increased size of coronoid notch, lateral bowing of ramus - Neurofibroma involving articular disc of TMJ has been reported Javed et al. Critical Reviews in Oncology / Hematology (2014) Approximately 72% of affected individuals exhibit oral manifestations. #### Gingival Enlargement and Pigmentation - Common in children with NF1. - Presents as diffuse, unilateral enlargement of the attached gingiva. - The tissue is fibrous and does not exhibit signs of inflammation. - Rare cases may show melanin pigmentation of the gingiva. #### Dental Abnormalities - Impacted, supernumerary, missing, or displaced teeth. - Plexiform neurofibromas can be associated with aplasia of mandibular second molars, increased spacing between teeth, and jaw asymmetries. #### Soft Tissue and Osseous Lesions - **Neurofibromas:** Commonly affect the tongue; plexiform neurofibromas may result in macroglossia. - **Osseous Lesions:** Not very common but unique to the individual. Features may include increased size of the coronoid notch and lateral bowing of the ramus. - **TMJ:** Neurofibroma involving the articular disc of the temporomandibular joint has been reported. # Diagnosis ## Solitary: - Histopathological evaluation ## NF-1: - Clinical diagnosis of NF-1 based on criteria set by National Institutes of Health Conensus Conference in 1987 - At least two major disease features out of the following: - A first-degree relative with NF1, six or more cafe' au lait patches >5 mm in greatest diameter in prepubertal individuals, and >15 mm in greatest diameter in postpubertal individuals - Axillary or groin freckling, two or more neurofibromas, or one plexiform neurofibroma - Two or more Lisch nodules in the iris - Optic pathway glioma - A distinctive osseous lesion, including bony dysplasia of the sphenoid wing, or pseudoarthrosis of the long bones #### Diagnostic Criteria **Solitary Lesions:** - Diagnosed via histopathological evaluation. **NF-1 Clinical Diagnosis:** Based on the 1987 National Institutes of Health Consensus Conference, diagnosis requires at least two of the following major features: 1. A first-degree relative with NF1. 2. Six or more café-au-lait patches (>5 mm in prepubertal individuals; >15 mm in postpubertal individuals). 3. Axillary or groin freckling. 4. Two or more neurofibromas or one plexiform neurofibroma. 5. Two or more Lisch nodules in the iris. 6. Optic pathway glioma. 7. A distinctive osseous lesion (e.g., bony dysplasia of the sphenoid wing or pseudoarthrosis of the long bones). # Management Solitary: - Complete excision - 5% recurrence rate due to incomplete excision - Malignant transformation rare Early detection of potential treatable complications Neurofibromas - Dermal neurofibromas - Surgical removal, laser ablation for small lesions, electrodesiccation - Plexiform neurofibromas - Pain management, excision of surgically amenable tumours - Many biologically targeted therapies (mTOR inhibitors, imatinib, selective MEK inhibitors) that inhibit pathways responsible for tumour growth evaluated - Atypical neurofibromas - Symptomatic neurofibromas revealing hypercellularity and atypical nuclei, few mitoses, no necrosis : suggestive as pre-malignant - Complete excision and clinical surveillance - MPNST - Complete excision, neoadjuvant chemotherapy Gutman D et al. Neurofibromatosis type 1. Nature Reviews Disease Primer. 2017 #### Management of Solitary Neurofibroma - Complete excision is the standard treatment. - There is a 5% recurrence rate, usually due to incomplete excision. - Malignant transformation is rare. #### Management of NF-1 Complications Early detection of treatable complications is essential. - **Dermal Neurofibromas:** Surgical removal, laser ablation for small lesions, or electrodesiccation. - **Plexiform Neurofibromas:** Pain management and excision of surgically amenable tumours. Biologically targeted therapies (mTOR inhibitors, imatinib, selective MEK inhibitors) are being evaluated. - **Atypical Neurofibromas:** Symptomatic lesions showing hypercellularity and atypical nuclei are suggestive of pre-malignancy. These require complete excision and clinical surveillance. - **MPNST:** Treated with complete excision and neoadjuvant chemotherapy. # Neurilemoma - Schwannoma - Most common benign neurogenic neoplasms - Neoplastic proliferation comprised exclusively of cells that resemble Schwann cells and have antigenic phenotype of Schwann cells ## Aetiology - 90% are sporadic - Can occur in specific syndromes – NF2 (3%), Schwannomatosis (2%), Carney complex - Genetic ## Clinical Presentation: - Majority are non-vestibular or extracranial - Solitary - Encapsulated masses of long duration at time of presentation - Rarely show rapid growth course - Painless and not ulcerated - Can manifest with facial hypoesthesia, paraesthesia, or pain - Bilateral schwannomas related to NF-2 <img src="https://i.imgur.com/8Z9vLzQ.jpg" alt="Image of a buccal mucosa lesion near the teeth, labeled 'a'."/>  tumours_slides_figures/img_721e41db55d68201.webp) Neurilemoma (Schwannoma) is the most common benign neurogenic neoplasm. It is a neoplastic proliferation comprised exclusively of cells that resemble Schwann cells and possess the corresponding antigenic phenotype. #### Aetiology - 90% of cases are sporadic. - Can occur in specific syndromes: NF2 (3%), Schwannomatosis (2%), and Carney complex. - Genetic factors play a role. #### Clinical Presentation - Majority are non-vestibular or extracranial. - Typically presents as a solitary, encapsulated mass of long duration. - Rapid growth is rare. - Usually painless and not ulcerated. - May manifest with facial hypoesthesia, paraesthesia, or pain. - Bilateral schwannomas are specifically related to NF-2. A close-up photo of a buccal mucosa lesion near the teeth, labeled 'a', showing a pink, raised mass on the inner cheek. This image is associated with the clinical presentation of neurilemoma, specifically illustrating a lesion that may manifest as facial hypoesthesia, paraesthesia, or pain. # Neurofibromatosis type 2 Characterised by development of: - Schwannomas - Meningiomas - Ependymomas Majority of patients developing bilateral schwannoma involving superior vestibular branch of 8<sup>th</sup> cranial nerve - Hearing loss, tinnitus, imbalance Although disease classified as “neurofibromatosis”, neurofibromas are relatively infrequent Dominantly inherited tumour predisposition syndrome caused by mutations in NF2 gene on chromosome 22 Evans DGR. Neurofibromatosis type 2 (NF2): A clinical and molecular review. Orphanet Journal of Rare Diseases. 2009;4:16 Neurofibromatosis type 2 (NF2) is a dominantly inherited tumour predisposition syndrome caused by mutations in the NF2 gene on chromosome 22. Although classified as a "neurofibromatosis," actual neurofibromas are relatively infrequent in this condition. #### Characteristic Tumours - Schwannomas - Meningiomas - Ependymomas #### Clinical Features - The majority of patients develop bilateral schwannomas involving the superior vestibular branch of the 8th cranial nerve. - Symptoms include hearing loss, tinnitus, and imbalance. # Neurilemoma ## Histopathology - Encapsulated - Two main patterns observed: Antoni A and Antoni B types - Antoni A: highly cellular, composed of elongated Schwann cells exhibiting area of organized spindle-shaped cells in a palisading arrangement around acellular, eosinophilic areas forming Verocay bodies - Antoni type B: composed of elongated Schwann cells, arranged in less dense myxoid manner, more disorganised compared to Antoni A - Cystic change becomes more prominent as tumour enlarges and is associated with mucinous degeneration, haemorrhage, necrosis, microcystic formation <img src="https://i.imgur.com/placeholder.jpg" alt="Microscopic images of neurilemoma tissue sections labeled h and i" />  tumours_slides_figures/img_dbf3bda4053d0a9c.webp) #### Histopathology Neurilemomas are encapsulated and typically exhibit two main patterns: - **Antoni A:** Highly cellular area composed of elongated Schwann cells. It features organized spindle-shaped cells in a palisading arrangement around acellular, eosinophilic areas known as Verocay bodies. - **Antoni B:** Composed of elongated Schwann cells arranged in a less dense, more disorganized myxoid manner compared to Antoni A. As the tumour enlarges, cystic change becomes more prominent, often associated with mucinous degeneration, haemorrhage, necrosis, and microcystic formation. Microscopic images of neurilemoma tissue sections labeled h and i, showing histopathological features. Image h displays the Antoni A pattern with highly cellular, organized spindle-shaped cells in a palisading arrangement around acellular, eosinophilic areas forming Verocay bodies. Image i illustrates the Antoni B pattern with less dense, myxoid, and more disorganized elongated Schwann cells. # Neurilemoma ## Diagnosis - Histopathological evaluation ## Management - Complete resection curative, not likely to recur - Malignant transformation has not been reported - Depending on location of lesion – possible risk to major nerve or other vital structures, possible to opt for close follow-up observation #### Diagnosis - Diagnosis is confirmed through histopathological evaluation. #### Management - Complete resection is curative; the lesion is not likely to recur. - Malignant transformation has not been reported. - Depending on the location and potential risk to major nerves or vital structures, clinicians may opt for close follow-up observation instead of immediate surgery. # Lipoma - A rare, benign tumour of the adipose tissue. ## Epidemiology - More common in men. - Most frequent benign mesenchymal tumour. - 15-20% occur in the head and neck. - Intra oral lesions are less frequent, representing 1-4% of head and neck lipomas. - Often seen in overweight individuals. ## Aetiopathogenesis - Well-circumscribed benign neoplastic proliferations of adipose tissue. Lipoma is a rare, benign tumour of the adipose tissue. #### Epidemiology and Prevalence - Most frequent benign mesenchymal tumour. - More common in men. - Often seen in overweight individuals. - 15-20% of cases occur in the head and neck region. - Intra-oral lesions are less frequent, representing 1-4% of head and neck lipomas. #### Aetiopathogenesis - These lesions are well-circumscribed benign neoplastic proliferations of adipose tissue. # Lipoma ## Clinical Presentation - Slow growing, yellowish, soft, semi-fluctuant, painless mass. - Usually seen on the buccal mucosa, followed by tongue, lips and floor of mouth. - Covered by normal mucosa or skin. - Can be solitary or multiple. - Size of lesions vary, with an average size of 2cm. ## Histopathology - Proliferation of mature adipocytes - Paucicellular fibrous septa can be present - Fat necrosis is often found in larger tumor ## Diagnosis - Lesions demonstrate characteristic low attenuation on CT and signal intensity is similar to that of fat on all MRI sequences. - A biopsy is diagnostic, that typically exhibit connective tissue capsule circumscribing lobules of hexagonal cells that resemble normal adipose tissue. - Patients with multiple lesions in the body should be investigated for syndromes and rare obesity disorders. ## Management - Excisional biopsy - Recurrence is not likely - Adequate imaging, diagnostic biopsy and careful assessment paramount before surgery planned of large and difficult to access lesions. <img src="https://i.imgur.com/1Q0lZ5r.jpg" alt="Clinical image of lipoma in oral cavity"/> <img src="https://i.imgur.com/5Z6zVqW.jpg" alt="Histopathological slide of lipoma"/>  tumours_slides_figures/img_527b0684ed0c6a68.webp)  tumours_slides_figures/img_e62d907b7c33d6b2.webp) #### Clinical Presentation - **Physical Characteristics**: Slow-growing, yellowish, soft, semi-fluctuant, and painless mass. - **Common Sites**: Usually seen on the buccal mucosa, followed by the tongue, lips, and floor of the mouth. - **Appearance**: Covered by normal mucosa or skin; can be solitary or multiple. - **Size**: Lesions vary in size, with an average diameter of 2cm. #### Histopathology - Characterized by the proliferation of mature adipocytes. - Paucicellular fibrous septa may be present. - Fat necrosis is often found in larger tumours. #### Diagnostic Evaluation - **Imaging**: Lesions demonstrate characteristic low attenuation on CT. Signal intensity is similar to that of fat on all MRI sequences. - **Biopsy**: A diagnostic biopsy typically exhibits a connective tissue capsule circumscribing lobules of hexagonal cells that resemble normal adipose tissue. - **Systemic Considerations**: Patients presenting with multiple lesions throughout the body should be investigated for syndromes and rare obesity disorders. #### Management and Prognosis - **Surgical Intervention**: Treatment consists of an excisional biopsy. - **Pre-surgical Planning**: Adequate imaging, diagnostic biopsy, and careful assessment are paramount before planning surgery for large or difficult-to-access lesions. - **Recurrence**: Recurrence is unlikely following excision. Clinical image of a lipoma in the oral cavity, showing a yellowish, soft, painless mass on the buccal mucosa, consistent with the described clinical presentation of a slow-growing lipoma. Histopathological slide of a lipoma, illustrating the proliferation of mature adipocytes with paucicellular fibrous septa, as described in the histopathology section. # Hemangioma - True neoplasms of blood vessels formed by endothelial proliferation assuming variable width - Aetiology & Pathogenesis: - Originate from embryonic placental angioblasts or intrinsic endothelial progenitor cells with the ability to clonally duplicate in a precise environment of cytokines and oestrogen concentration - Arise from progenitor cells with directional preponderance to become placental-like tissue in specific organs such as skin and liver - Role of molecular signalling involved in vascularization - Increased levels of common molecular contributions to endothelial cell migration and new vessel development have been discovered during proliferative phase of haemangioma growth as vascular endothelial growth factor (VEGF), basic fibroblast growth, insulin-like growth factor, matrix metalloprotease – 9. Hemangiomas are true neoplasms of blood vessels formed by endothelial proliferation assuming variable width. #### Aetiology and Pathogenesis - Hemangiomas originate from embryonic placental angioblasts or intrinsic endothelial progenitor cells. These cells possess the ability to clonally duplicate within a precise environment influenced by cytokines and oestrogen concentrations. - They arise from progenitor cells with a directional preponderance to become placental-like tissue in specific organs, such as the skin and liver. - Molecular signalling plays a significant role in vascularization. During the proliferative phase of growth, increased levels of molecular contributors to endothelial cell migration and new vessel development are present, including: - Vascular endothelial growth factor (VEGF) - Basic fibroblast growth factor - Insulin-like growth factor - Matrix metalloprotease-9 # Hemangioma ## Clinical Features - Proliferate 9 – 12 months of life and subsequently involute at a variable course over many years - Female predominance - Infantile hemangioma develops shortly after birth (60% occur in head and neck region) - Congenital hemangioma are rare, present at birth, does not follow natural growth phase - Smooth, reddish, purple, sessile, polypoid, or pedunculated masses, often with increasing size and occasional bleeding - Infantile hemangiomas are evident shortly after birth as well demarcated, red, vertically expansive lesions <img src="https://i.imgur.com/8JZjKzq.jpg" alt="Image of infantile hemangioma on the oral cavity"></img>  tumours_slides_figures/img_070d158fa0a4f6db.webp) #### Clinical Presentation and Progression - Hemangiomas typically proliferate during the first 9–12 months of life and subsequently involute over a variable course lasting many years. - There is a noted female predominance. - Infantile hemangiomas develop shortly after birth, with 60% occurring in the head and neck region. They appear as well-demarcated, red, vertically expansive lesions. - Congenital hemangiomas are rare, present at birth, and do not follow the natural growth phase of infantile types. - Physical characteristics include smooth, reddish, purple, sessile, polypoid, or pedunculated masses. These often increase in size and may exhibit occasional bleeding. A close-up photo of an infantile hemangioma on the oral cavity, showing a reddish, smooth, sessile mass on the tongue. The lesion is well-demarcated and appears to be a common presentation of infantile hemangioma, which typically develops shortly after birth and is often found in the head and neck region. # Hemangioma ## Histopathology - Classified according to the lumina of the capillary vessels that are predominant in the lesion - Capillary hemangiomas consist of multilobular arrangements of proliferating endothelial cells and capillaries of various shapes and sizes surrounded by pericytes - Appears more cellulary rich, mitotic activity is similar to cavernous type - Cavernous hemangiomas found in penial cavernous body and show larger dilated vascular spaces lined by endothelial cells - Final diagnosis may require immunohistochemical panel <img src="https://i.imgur.com/7XQzJzL.png" alt="Microscopic image of hemangioma tissue, labeled 'b'">  tumours_slides_figures/img_1df8b3177be50eaf.webp) #### Histopathological Classification Hemangiomas are classified according to the predominant lumina of the capillary vessels within the lesion. - **Capillary Hemangiomas**: Consist of multilobular arrangements of proliferating endothelial cells and capillaries of various shapes and sizes, surrounded by pericytes. These appear more cellularly rich, though mitotic activity is similar to the cavernous type. - **Cavernous Hemangiomas**: Found in the penial cavernous body, these show larger dilated vascular spaces lined by endothelial cells. #### Diagnostic Confirmation - A final diagnosis may require an immunohistochemical panel to differentiate the vascular structure. Microscopic image of hemangioma tissue, labeled 'b', showing multilobular arrangements of proliferating endothelial cells and capillaries with various shapes and sizes, surrounded by pericytes, consistent with capillary hemangioma histopathology. # Hemangioma ## Diagnosis - History. - Clinical examination including diascopy. - Biopsy is NOT indicated due to bleeding risk. - Investigations including imaging or angiography. ## Management - Small hemangiomas need no treatment – self involute by age 9 - Laser therapy - Corticosteroids #### Diagnostic Approach - **History and Clinical Examination**: Includes the use of diascopy. - **Biopsy**: Generally NOT indicated due to the significant risk of bleeding. - **Investigations**: May include specialized imaging or angiography. #### Management Strategies - **Observation**: Small hemangiomas often require no treatment as they typically self-involute by age 9. - **Laser Therapy**: Utilized for specific lesion types or locations. - **Pharmacotherapy**: Use of corticosteroids. # Rhabdomyosarcoma - Malignant neoplasms of skeletal striated muscle cells - Most common in children and adolescents (5-8% of all childhood malignancies) ## Aetiology - Sporadic presentation - Small subset of patients, part of genetic syndrome - Beckwith-Wiedeman - Von Reclighausen disease - Gorlin Rhabdomyosarcoma represents a group of malignant neoplasms derived from skeletal striated muscle cells. It is recognized as the most common soft tissue sarcoma in children and adolescents, accounting for approximately 5-8% of all childhood malignancies. #### Aetiology and Genetic Associations While most cases present sporadically, a small subset of patients develops the condition as part of a genetic syndrome, including: - Beckwith-Wiedemann syndrome - Von Recklinghausen disease (Neurofibromatosis type 1) - Gorlin syndrome (Basal cell nevus syndrome) # Rhabdomyosarcoma ## Clinical Features Three subsites based on anatomic location and local relapse - Parameningeal including paranasal sinuses, nasopharynx, nasal cavity, pterygopalatine, oral cavity - Palpable, circumscribed, rapidly growing mass ## Histopathology - 3 microscopic subtypes: - **Alveolar**: sheets of small, round cells clustered with variable amounts of fibrous septa; may contain scattered giant cells - **Embryonal**: cytologically round to spindle cells with scant cytoplasm in a myxoid background; elongated cells with more abundant eosinophilic cytoplasm referred to as "strap" cells or "tadpole" cells - **Pleomorphic**: sheets of large cells demonstrating marked nuclear atypia or "anaplasia" with eosinophilic cytoplasm <img src="https://i.imgur.com/8Z5ZzXJ.png" alt="Microscopic image of rhabdomyosarcoma tissue showing cellular morphology." />  tumours_slides_figures/img_2f6794e27bbdbf55.webp) #### Clinical Features Clinical presentation typically involves a palpable, circumscribed, and rapidly growing mass. The disease is categorized into three subsites based on anatomic location and the risk of local relapse: - Parameningeal sites: including the paranasal sinuses, nasopharynx, nasal cavity, and pterygopalatine fossa. - Oral cavity sites. #### Histopathology There are three primary microscopic subtypes of rhabdomyosarcoma: 1. **Alveolar**: Characterized by sheets of small, round cells clustered with variable amounts of fibrous septa. Scattered giant cells may be present. 2. **Embryonal**: Features cytologically round to spindle cells with scant cytoplasm set within a myxoid background. Elongated cells with more abundant eosinophilic cytoplasm are referred to as "strap" or "tadpole" cells. 3. **Pleomorphic**: Consists of sheets of large cells demonstrating marked nuclear atypia or "anaplasia" with eosinophilic cytoplasm. Microscopic image of rhabdomyosarcoma tissue showing cellular morphology with densely packed blue-stained nuclei and eosinophilic cytoplasm, illustrating the histopathological features described in the text. # Rhabdomyosarcoma ## Diagnosis - Histopathological assessment ## Treatment - Challenging due to an increased failure of local control - High rate of early metastases and recurrence rate - Surgery, chemotherapy, radiotherapy #### Diagnosis Diagnosis is established through comprehensive histopathological assessment. #### Treatment and Prognosis Management of rhabdomyosarcoma is challenging due to an increased risk of local control failure. The condition is characterized by a high rate of early metastases and recurrence. Treatment typically involves a multimodal approach: - Surgery - Chemotherapy - Radiotherapy # Fibrosarcoma - Malignant neoplasm of mesenchymal origin - Fibroblasts are the cell of origin - Arise in soft tissue or within the bone ## Clinical Features - Pain, Swelling, paraesthesia, and occasionally loss of teeth and ulceration of overlying mucosa - High local recurrence - Hematogenous metastasis may involve the lungs, mediastinum, abdominal cavity, bone - Innocuous, lobulated, sessile, painless, nonhemorrhagic submucosal mass of normal colouration Fibrosarcoma is a malignant neoplasm of mesenchymal origin where fibroblasts serve as the cell of origin. These tumors can arise within soft tissue or within the bone. #### Clinical Presentation Common clinical signs and symptoms include: - Pain and swelling - Paraesthesia - Occasional loss of teeth - Ulceration of the overlying mucosa In some instances, the lesion may appear as an innocuous, lobulated, sessile, and painless submucosal mass of normal coloration without hemorrhage. #### Progression and Metastasis Fibrosarcoma is associated with a high rate of local recurrence. Hematogenous metastasis may occur, frequently involving the following sites: - Lungs - Mediastinum - Abdominal cavity - Bone # Fibrosarcoma ## Histopathology - Highly cellular fibroblastic proliferation in herringbone pattern (cells in columns of short parallel lines with all the lines in one column sloping one way and lines in adjacent columns sloping the other way) - Cells have scant cytoplasm, tapering elongated dark nuclei with increased granular chromatin, variable nucleoli - Mitotic activity present, often with abnormal forms - Variable collagen - Usually no giant cells - No pleomorphism (or call pleomorphic MFH), no other distinct cell types - Patterns: - Keloid-like (thick hyalinized collagen fibers), loose fascicular, focally myxoid <img src="https://i.imgur.com/5QZJjXe.png" alt="Microscopic image of fibrosarcoma tissue showing cellular proliferation and herringbone pattern." />  tumours_slides_figures/img_82e146c5a1c0db96.webp) #### Microscopic Characteristics Fibrosarcoma is characterized by a highly cellular fibroblastic proliferation typically arranged in a "herringbone" pattern. This pattern consists of cells in columns of short parallel lines, where lines in one column slope in one direction while lines in adjacent columns slope the opposite way. Key histological features include: - Cells with scant cytoplasm and tapering, elongated dark nuclei. - Increased granular chromatin and variable nucleoli. - Presence of mitotic activity, often including abnormal forms. - Variable amounts of collagen. - Absence of giant cells and significant pleomorphism (the presence of which might suggest pleomorphic Malignant Fibrous Histiocytoma). #### Histological Patterns Observed growth patterns include: - Keloid-like (featuring thick hyalinized collagen fibers) - Loose fascicular - Focally myxoid Microscopic image of fibrosarcoma tissue showing highly cellular fibroblastic proliferation in a herringbone pattern, with cells arranged in columns of short parallel lines. The image illustrates the characteristic histopathological features described in the text, including scant cytoplasm, elongated nuclei, and variable collagen content. # Fibrosarcoma ## Diagnosis - Local extent of the neoplasm and the presence or absence of local and distant metastasis needs to be determined - Imaging: CT or MRI - Histopathology: low grade and high grade ## Treatment - Wide local excision, at least 1 cm of margin confirmed by histopathologic clearance - Radiotherapy - Chemotherapy #### Diagnostic Evaluation It is essential to determine the local extent of the neoplasm and the presence or absence of local and distant metastasis. - **Imaging**: CT or MRI is utilized for staging. - **Grading**: Histopathology classifies the tumor into low-grade and high-grade variants. #### Management Treatment strategies include: - **Wide local excision**: Requiring at least a 1 cm margin confirmed by histopathologic clearance. - **Radiotherapy** - **Chemotherapy** # Kaposi Sarcoma - Angioproliferative malignant neoplasia of endothelial cells forming an infiltrative capillary-rich lesion that eventually disseminates to multiple cutaneous sites, viscera, and lymph nodes ## Aetiology & Pathogenesis - Caused by HHV8 infection of endothelial cells - Found in immunocompetent people and is active in immunosuppression - Tat protein produced by lymphoid cells infected with HIV promoted the infection of HHV8 contributing to the highly aggressive nature of AIDS-KS by inducing inflammatory cytokines and angiogenesis Kaposi Sarcoma is an angioproliferative malignant neoplasia of endothelial cells. It forms an infiltrative, capillary-rich lesion that eventually disseminates to multiple cutaneous sites, viscera, and lymph nodes. #### Aetiology and Pathogenesis The condition is caused by Human Herpesvirus 8 (HHV8) infection of endothelial cells. While it can be found in immunocompetent individuals, it is significantly more active during immunosuppression. In AIDS-related Kaposi Sarcoma (AIDS-KS), the Tat protein produced by HIV-infected lymphoid cells promotes HHV8 infection. This contributes to the highly aggressive nature of the disease by inducing inflammatory cytokines and angiogenesis. # Kaposi Sarcoma ## Clinical Features - second most frequent tumour in HIV-infected patients worldwide - Most common cancer in Sub-Saharan Africa - Most affected oral location: hard palate → gingiva → tongue - 70% of patients with cutaneous AIDS-related KS also have oral lesions - Multiple patches, and papules with bluish to purple colour are the most common skin and mucosal presentations - Develop to more nodular stage as it progresses - Hemorrhage, pain, ulceration, secondary infections as it advances - Highly aggressive lesions are infiltrative, involve soft tissue and bone - Can disseminate compromising visceral organs and lymphatic nodes <img src="https://i.imgur.com/1vXkZ5L.jpg" alt="Oral lesion of Kaposi Sarcoma" /> <img src="https://i.imgur.com/8Q7Z6fJ.jpg" alt="Advanced oral lesion of Kaposi Sarcoma" />  tumours_slides_figures/img_4e0154e0607c4cad.webp)  tumours_slides_figures/img_ac25afea642c3a2b.webp) #### Clinical Presentation and Epidemiology Kaposi Sarcoma is the second most frequent tumor in HIV-infected patients worldwide and the most common cancer in Sub-Saharan Africa. - **Oral Manifestations**: The most common oral locations are the hard palate, followed by the gingiva and the tongue. Approximately 70% of patients with cutaneous AIDS-related KS also present with oral lesions. - **Appearance**: Common presentations include multiple patches and papules with a bluish to purple color. As the disease progresses, these lesions transition into a nodular stage. - **Advanced Symptoms**: Advanced lesions may exhibit hemorrhage, pain, ulceration, and secondary infections. - **Aggressive Behavior**: Highly aggressive lesions are infiltrative, involving both soft tissue and bone, and can disseminate to compromise visceral organs and lymphatic nodes. Oral lesion of Kaposi Sarcoma showing multiple bluish to purple patches and papules on the hard palate, consistent with the clinical features described in the text. Advanced oral lesion of Kaposi Sarcoma displaying a more nodular and infiltrative stage with significant hemorrhage, ulceration, and tissue involvement, illustrating the progression of the disease. # Kaposi Sarcoma ## Histopathology ### Early “Patch-Stage” lesion - Proliferation of small and jagged endothelial-lined spaces surrounding normal dermal vessels and irregularly shaped - Slit-like vascular spaces dissecting collagen bundles, parallel to the endothelium - Extravasated erythrocytes and lymphocytes ### Advanced stage - Accumulation of spindle-shaped cells, which are considered to be tumour cells of KS - Intra and extracellular hyaline globules and increased mitotic activity <img src="https://i.imgur.com/2a.png" alt="Microscopic images of Kaposi Sarcoma lesions labeled 2a, 2b, 2c, and 2d" /> Temelkova, Ivanka & Tronnier, Michael & Terziev, Ivan & Wollina, Uwe & Lozev, Ilia & Goldust, Mohamad & Tchernev, Georgi. (2018). A Series of Patients with Kaposi Sarcoma (Mediterranean/Classical Type): Case Presentations and Short Update on Pathogenesis and Treatment of the Creative Commons Attribution-  tumours_slides_figures/img_a0661cbc09385539.webp) #### Histopathological Stages **Early "Patch-Stage" Lesion** - Characterized by the proliferation of small, jagged, endothelial-lined spaces surrounding normal dermal vessels. - Slit-like vascular spaces dissecting collagen bundles, running parallel to the endothelium. - Presence of extravasated erythrocytes and lymphocytes. **Advanced Stage** - Accumulation of spindle-shaped cells, which are considered the primary tumor cells of Kaposi Sarcoma. - Presence of intra- and extracellular hyaline globules. - Increased mitotic activity. Microscopic images of Kaposi Sarcoma lesions labeled 2a, 2b, 2c, and 2d, showing histopathological features of early patch-stage and advanced stages, including proliferating endothelial-lined spaces, slit-like vascular spaces, and spindle-shaped cells. # Kaposi Sarcoma ## Diagnosis - HHV8 positive peripheral blood, as well as lesional tissue ## Treatment - Local excision, radiation therapy, chemotherapy, and the adjustment of immunosuppressive medications can all be considered - Local recurrence is common in AIDS-KS patients, but survival is more related to the immunological status of these patients; the mortality rate can reach 20–25%. #### Diagnosis Diagnosis is supported by identifying HHV8 in peripheral blood as well as within the lesional tissue. #### Treatment and Prognosis Management options include: - Local excision - Radiation therapy - Chemotherapy - Adjustment of immunosuppressive medications While local recurrence is common in AIDS-KS patients, overall survival is closely linked to the patient's immunological status. In advanced or aggressive cases, the mortality rate can reach 20–25%. Thank you for listening lalima.tiwari@uwa.edu.au Thank you for listening. For further inquiries or information, please contact: lalima.tiwari@uwa.edu.au [^1]: Original PDF page 1: [[L14 Soft tissue (mesenchymal) tumours_slides.pdf#page=1|L14 Soft tissue (mesenchymal) tumours slides, p.1]] [^2]: Original PDF page 2: [[L14 Soft tissue (mesenchymal) tumours_slides.pdf#page=2|L14 Soft tissue (mesenchymal) tumours slides, p.2]] [^3]: Original PDF page 3: [[L14 Soft tissue (mesenchymal) tumours_slides.pdf#page=3|L14 Soft tissue (mesenchymal) tumours slides, p.3]] [^4]: Original PDF page 4: [[L14 Soft tissue (mesenchymal) tumours_slides.pdf#page=4|L14 Soft tissue (mesenchymal) tumours slides, p.4]] [^5]: Original PDF page 5: [[L14 Soft tissue (mesenchymal) tumours_slides.pdf#page=5|L14 Soft tissue (mesenchymal) tumours slides, p.5]] [^6]: Original PDF page 6: [[L14 Soft tissue (mesenchymal) tumours_slides.pdf#page=6|L14 Soft tissue (mesenchymal) tumours slides, p.6]] [^7]: Original PDF page 7: [[L14 Soft tissue (mesenchymal) tumours_slides.pdf#page=7|L14 Soft 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