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Correct answer is NF2 Schwannoma Genetic Mutations Schwannomas are benign nerve sheath tumors associated with key genetic alterations: 1. NF2 Gene (22q12): Encodes Merlin. Loss-of-function mutations cause unregulated cell growth, central to Neurofibromatosis Type 2 (NF2) with bilateral vestibular schwannomas. 2. SMARCB1 Gene: Mutations linked to familial/sporadic schwannomatosis, marked by non-vestibular schwannomas and chronic pain. 3. LZTR1 Gene (22q): Regulates Ras/MAPK pathway. Mutations are associated with schwannomatosis. 4. Chromosomal Aberrations: Monosomy 22 or deletions highlight NF2 loss in sporadic schwannomas. Reference: Evans DG, The Lancet, 2009;373(9679):1974-1986.

Nodular fascitis

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Very useful.. Graet tips... Keep going.. Many thanks

crohns

Retinoblastoma

Nodular sclerosis HL

Diagnosis in this case is extraskeletal medicinal chondrosarcoma Common genetic alteration identified is EWSR1- NR4A3 fusion To differentiate Extraskeletal Myxoid Chondrosarcoma (EMC) from its mimics such as low-grade myxofibrosarcoma, myxoid liposarcoma, and low-grade fibromyxoid sarcoma, a combination of histological, immunohistochemical, and molecular features is critical: Extraskeletal Myxoid Chondrosarcoma (EMC) • Histology: Tumor cells arranged in cords or clusters within abundant myxoid stroma divided by fibrous septa. 🧬 • Immunohistochemistry: Focal S100 positivity, EMA positivity, and consistently positive for vimentin. 🧪 • Molecular Features: Defined by EWSR1-NR4A3 fusion, detected by FISH or RT-PCR. 🔬 Few differentials include: Myxoid Liposarcoma (MLS) • Histology: Lipoblasts within a myxoid stroma and a characteristic “chicken-wire” vascular pattern. 🐓 • Immunohistochemistry: S100 positive (in lipoblasts) and MDM2 negative. ✅🚫 • Molecular Features: FUS-DDIT3 or EWSR1-DDIT3 fusion, diagnostic. 📌 Low-Grade Fibromyxoid Sarcoma (LGFMS) • Histology: Bland spindled cells with alternating fibrous and myxoid areas. 🔄 • Immunohistochemistry: Negative for S100 and EMA, but positive for MUC4. ✅ • Molecular Features: FUS-CREB3L2 fusion (t(7;16)(q32-34;p11)) in 90%, a key diagnostic feature. 💯 Defining Features of EMC • EWSR1-NR4A3 fusion 🧬 • Cord-like tumor arrangement 🧵 • Lobular architecture 🪆 These characteristics, particularly molecular testing, are essential for definitive diagnosis. ✅

Rheumatoid nodule

T cell lymphoma

Correct answer is Angioimmunoblastic T cell lymphoma

Rheumatoid nodule Or Necrobiotic granuloma .... how to differentiate between the two?

Diagnosis is Angioimmunoblastic T-cell Lymphoma Histologic Features: Architecture: Effacement of lymph node architecture with a polymorphous infiltrate. Cell Types: Composed of atypical lymphocytes, prominent high endothelial venules (HEV), and proliferation of follicular dendritic cells. Infiltration: Presence of reactive B-cells, plasma cells, and often eosinophils within the background. Characteristic Features: Arborizing blood vessels (branching HEVs) and increased follicular dendritic cell meshwork. Immunohistochemistry (IHC) Markers • T-cell markers: Positive for CD3, CD4, and CD10, often with co-expression of PD-1 and CXCL13. Follicular Helper T-cell Markers: Positive for BCL-6, ICOS, and CXCL13, supporting follicular helper T-cell origin. EBV: Epstein-Barr virus (EBV) is often present in B-cells (detected by EBER in-situ hybridization). CD21 and CD23: Highlight follicular dendritic cell networks, often expanded and prominent. Other markers: Positive for CD30 in some cases, which may indicate reactive immunoblasts.

Angioimmunoblastic T cell lymphoma

Micropapillary urothelial carcinoma is an aggressive subtype of bladder cancer with distinct features. Here’s what you need to know: • Small clusters of tumor cells without fibrovascular cores, often surrounded by lacunae. 🧬 • Multiple clusters within the same lacuna are typical. • Tumor cells have peripherally oriented nuclei and occasional cytoplasmic vacuoles (ring forms). 🔬 • Lymphovascular invasion is common, with CIS present in more than half of cases. • ERBB2 overexpression/amplification could be a potential therapy target. 🎯 • Radical cystectomy may be considered for non-muscle-invasive bladder cancer with substantial micropapillary components. 🏥

Correct answer is follicular lymphoma ✅Histopathology: Neoplastic follicles with centrocytes and centroblasts; graded 1-3 based on centroblast count. ✅Immunophenotype: Positive for CD20, CD10, BCL-6, and BCL-2; low Ki-67 proliferation index. ✅Genetics: t(14;18) translocation leads to BCL-2 overexpression, preventing apoptosis. ✅Presentation: Painless lymphadenopathy; systemic symptoms are rare. ✅Prognosis/Treatment: Indolent course; treated with rituximab, chemotherapy, or radiotherapy; targeted therapies for refractory cases. ✅Transformation: Risk of transformation to DLBCL, leading to more aggressive disease and treatment requirements.

Retinoblastoma , grade 3

Retinoblastoma

How would you histologically grade this tumor? A. G1 B. G2 C. G3 D. G4

Correct answer is Hodgkins lymphoma. Nodular sclerosis subtype. Note the atypical mononuclear cells along with Classic Reed sternberg cells with owl eye appearance.

Hodgkin's lymphoma

Which of these is associated with this condition A. HTLV-1 B. EBV C. HHV 8 D. HSV

Correct answer is Hepatocellar carcinoma- more specifically, fibrolamellar variant of HCC. 🔑 points: Young age of Incidence. Background of collagen and fibrous bands. Cells with abundant eosinophilic cytoplasm and distinct cell borders. Pale bodies( though not diagnostic) Molecular alteration associated with Fibrolamellar HCC: DNAJB1-PRKARCA fusion gene.

Hcc?

ABC

Meningioma?

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Pseudoangiomatous stromal hyperplasia

Papillary ca of thyroid, follicular variant?

Correct answer is aneurysmal bone cyst (ABC). Findings in the image are classical of ABC. USP6 rearrangement is seen in these cases.

👾Granular cell tumors (GCTs) are rare, typically benign neoplasms that can arise in various tissues but most commonly occur in the skin, tongue, and subcutaneous tissues. Histologically, GCTs are characterized by the following features: - Granular cytoplasm: The cells have abundant granular eosinophilic cytoplasm, which is due to the presence of lysosomes. - Nuclei: The nuclei are small, round, and centrally located. - Cell arrangement: The cells are arranged in sheets, nests, or cords within a fibrous stroma. - Pseudoepitheliomatous hyperplasia: In some cases, especially in the skin and oral cavity, overlying squamous epithelium can exhibit hyperplasia, which can mimic squamous cell carcinoma. 🤖Immunohistochemistry (IHC) findings are crucial for diagnosing GCTs: - S100 protein: Strongly positive, indicating neural origin. - NSE (Neuron-Specific Enolase): Positive, supporting neural differentiation. - CD68: Positive, reflecting the lysosomal content of the cells. -Inhibin-alpha: Can be positive in some cases. These IHC markers help distinguish granular cell tumors from other neoplasms with similar histological appearances.

Sertoli cell tumors of the testis -! revision Read further to know more about Sertoli cell tumor variants and differentials 🎯Sertoli cell tumors Age of Presentation: Any age Clinical Features: Testicular pain or incidentally discovered mass. H/o infertility, cryptorchidism, Klinefelter syndrome. Histology: Sertoli-only tubular-trabecular nodules with thick basement membranes. Immunohistochemistry: Decreased androgen receptors, variable gain of calretinin, pankeratin, CD56. 🎯Large Cell Calcifying Sertoli Cell Tumors Age of Presentation: Usually less than 20 Clinical Features: Sporadic: 60%, syndromic: 40% (Carney, Peutz-Jeghers). Histology: Large eosinophilic/amphophilic cells in cords and trabeculae, sclerotic background, large layered calcium deposits, inflammation. Immunohistochemistry: Negative androgen receptors, strong diffuse calretinin, consistent S100. 🎯Sclerosing Sertoli Cell Tumors Age of Presentation: 35 (mean postpubertal) Clinical Features: Young adults with testicular pain or incidentally discovered mass. Histology: Thick anastomosing cords of clear cells with abundant cytoplasm, second population of cells with scant cytoplasm in thin cords, tubules or pseudoalveolar patterns; prominent sclerotic and/or hyalinized background. Immunohistochemistry: Strong androgen receptors, negative inhibin, partial gain of PAX2/PAX8 and S100. 🎯Malignant Sertoli Cell Tumors Age of Presentation: Older age Clinical Features: Testicular pain/mass. Histology: Focal tubular differentiation, atypia, mitoses, necrosis, infiltrative growth pattern, angioinvasion, metastases. Immunohistochemistry: Markedly reduced androgen receptors, gain of neuroendocrine markers and pankeratin, aberrant expression of unusual markers (e.g., c-Kit). Reference WHO Tumors of the Urinary and male genital system 5th edition- 2022

Condyloma Acuminatum Common in upper anal canal Increased risk in immunodeficiency individuals Microscopic features include: Hyperplastic papillary exophytic squamous epithelium, Marked acanthosis, Parakeratosis, Fibrovascular core, Koilocytosis In anal condylomas of low grade dysplasia is present, the terminology LSIL (condyloma acuminatum)/ AIN (Anal intraepithelial neoplasia). Caused by Low risk HPV 6 and 11 Reference: WHO tumors of skin 5th edition 2022

Diagnosis is Pseudoangiomatous stromal Hyperplasia (PASH) ➡️PASH is a benign myofibroblastic proliferation of breast. 📩Histologic features include: Complex interanastomosing spaces in dense collagenous, keloid-like stroma Some of these spaces have spindle shaped myofibroblasts at their margins that simulate endothelial cells (hence the name Pseudoangiomatous) Gyenecomastoid changes 🧪Immunohistochemistry: CD 31 , Factor VIII and ERG negative in spindle cells while positive for CD 34 and ER Differential diagnosis: 1. Diabetic mastopathy (also has keloid like collagenous stroma) 2. Low grade angiosarcoma 3. Myofibroblastoma (epithelial components are rare in the tumor) Reference: WHO Breast tumors 2022 5th edition.

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