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I have enough information from the library and my own knowledge to give detailed answers. Let me now provide a comprehensive response to all 4 questions.
Here are the answers to all 4 questions with detailed explanations:
Question 1
A 38-year-old female with a subcutaneous mass near the left shoulder. Most appropriate immunomarker expression?
✅ Answer: B. CD34 positive & Rb loss
Reasoning:
The clinical scenario - a subcutaneous mass near the shoulder of a middle-aged woman - combined with the histological image showing a storiform/whorled spindle cell pattern is classic for Dermatofibrosarcoma Protuberans (DFSP).
- CD34 positive: DFSP is strongly and diffusely CD34 positive - a hallmark of the tumor. This distinguishes it from dermatofibroma (which is CD34 negative, Factor XIIIa positive).
- Rb loss: DFSP characteristically shows loss of Rb (retinoblastoma protein) expression by IHC, due to deletion of chromosome 13q (which harbors the Rb gene). This Rb loss is a useful distinguishing feature.
- S100 is negative in DFSP (rules out A and D).
- Rb is lost, not retained (rules out C and E).
Key molecular marker: COL1A1-PDGFB gene fusion (t17;22) - targeted by imatinib.
Question 2
Classic "fingerprint" pattern of CD34 IHC staining is seen in which tumor?
✅ Answer: C. Spindle cell lipoma
Reasoning:
The fingerprint pattern of CD34 staining is a well-recognized phenomenon in spindle cell lipoma (and pleomorphic lipoma, which is in the same spectrum). This refers to the characteristic wavy, curvilinear arrangement of CD34-positive spindle cells that resembles fingerprint whorls on IHC.
- DPSP: CD34 positive, but does not show a fingerprint pattern - it shows storiform/whorled pattern.
- Solitary fibrous tumor (SFT): CD34 positive (also STAT6 positive), but the classic fingerprint pattern is not ascribed to SFT.
- Neurofibroma: CD34 positive in some areas, S100 positive, but no fingerprint pattern.
- Schwannoma: S100 positive, CD34 negative (or weakly positive in Antoni B areas), no fingerprint pattern.
The "fingerprint" CD34 pattern is a distinctive feature taught specifically for spindle cell lipoma in surgical pathology.
Question 3
18-year-old male, thigh mass, spindle cells in fascicles, CD99+, EMA(focal)+, S100(diffuse moderate)+, INI-1 retained; negative for CD34, CD31, SMA, SOX10, desmin, myogenin, MDM2. Which immunomarker is likely positive?
✅ Answer: C. TLE1
Reasoning:
This is classic Synovial Sarcoma (monophasic):
- Young patient, deep soft tissue of thigh
- Spindle cells in fascicles with scant cytoplasm and ovoid hyperchromatic nuclei
- CD99 (diffuse strong) + EMA (focal) + S100 (moderate) + INI-1 retained
- Negative for CD34, SMA, desmin, myogenin (rules out other sarcomas)
- Low mitotic rate (1-2/10 HPF) consistent with monophasic SS
TLE1 (Transducin-like Enhancer of Split 1) is the most sensitive and specific IHC marker for synovial sarcoma (sensitivity ~95%, specificity ~92%). It is a nuclear stain reflecting the SS18-SSX gene fusion product's transcriptional activity.
- MUC1: Not specific for synovial sarcoma.
- STAT6: Marker of solitary fibrous tumor (NAB2-STAT6 fusion) - this tumor is CD34 negative, making SFT unlikely.
- TLE1: Correct - the hallmark IHC for synovial sarcoma.
- TFE3: Marker of alveolar soft part sarcoma (ASPS) or TFE3-rearranged tumors - different morphology (polygonal cells, organoid pattern), not spindle cell fascicular pattern.
- Nuclear beta-catenin: Marker of desmoid tumor/aggressive fibromatosis - typically SMA+ and beta-catenin mutation; also CTNNB1-mutated tumors.
Molecular confirmation: SS18-SSX1 or SS18-SSX2 fusion by FISH/RT-PCR.
Question 4
40-year-old female, right thigh mass; lobules of plump polygonal cells with abundant eosinophilic cytoplasm, vesicular nuclei, prominent nucleoli. IHC: S100 (diffuse)+, SOX10 (diffuse)+, EMA (focal)+, CD34 (focal)+; negative for pancytokeratin, MelanA, SMA, myogenin, CD31, CD30, desmin, INI-1. Diagnosis?
The options are cut off, but the answer is:
✅ Malignant Peripheral Nerve Sheath Tumor (MPNST) with epithelioid features - but more specifically this profile perfectly fits Epithelioid MPNST OR more likely given the INI-1 loss and S100/SOX10 diffuse positivity with EMA focal positivity - this is Epithelioid Malignant Peripheral Nerve Sheath Tumor (E-MPNST).
Wait - let me reconsider. INI-1 negative (loss) + S100 diffuse + SOX10 diffuse + EMA focal + polygonal/epithelioid cells with prominent nucleoli = Epithelioid MPNST
Key points:
- INI-1 loss (SMARCB1 deletion) is seen in ~50-80% of epithelioid MPNSTs - this is actually a defining/characteristic feature
- S100 and SOX10 diffuse positivity points strongly to nerve sheath origin
- MelanA negative excludes melanoma (which would also be S100+/SOX10+ but MelanA+)
- Pancytokeratin negative excludes carcinoma
- EMA focal can be seen in nerve sheath tumors
- CD34 focal may be seen
The diagnosis among the choices starting with "A. Melanoma" - the correct answer would NOT be melanoma (MelanA negative), and the diagnosis is most consistent with Epithelioid MPNST (answer likely option B, C, D, or E - the remaining options not visible in the image).
If the choices include "Epithelioid MPNST" - that is the answer. The INI-1 loss is the key distinguishing feature from schwannoma (which retains INI-1 and is S100+/SOX10+).
Summary Table
| Q | Answer | Diagnosis | Key Marker |
|---|---|---|---|
| 1 | B | DFSP | CD34+ & Rb loss |
| 2 | C | Spindle cell lipoma | CD34 fingerprint pattern |
| 3 | C | Synovial sarcoma | TLE1 |
| 4 | Epithelioid MPNST | E-MPNST | S100+/SOX10+ diffuse, INI-1 loss |
But mpnst has patchy s100
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epithelioid MPNST vs clear cell sarcoma S100 diffuse SOX10 INI-1 loss MelanA negative IHC differential
You're correct about conventional MPNST, but the sources confirm my diagnosis is still right - just for a specific reason. Here's the full clarification:
You Are Correct - With an Important Distinction
Conventional MPNST: S100 patchy/focal (~40% of cases), SOX10 weak/focal (~27%) - you're absolutely right about this.
However - Epithelioid MPNST (EMPNST) is a recognized distinct variant that breaks this rule:
- S100: diffuse and strong (unlike conventional MPNST)
- SOX10: diffuse (unlike conventional MPNST)
- INI-1 (SMARCB1): lost in ~50-80% - the key distinguishing feature
- MelanA/HMB45: negative (distinguishes from melanoma and clear cell sarcoma)
- Pancytokeratin: negative (distinguishes from carcinoma and epithelioid sarcoma)
This is exactly the profile in Question 4 - diffuse S100, diffuse SOX10, INI-1 loss, MelanA negative, pancytokeratin negative - which is the textbook fingerprint of Epithelioid MPNST.
Why not Clear Cell Sarcoma (the main mimic)?
| Feature | EMPNST | Clear Cell Sarcoma |
|---|---|---|
| S100 | Diffuse + | Diffuse + |
| SOX10 | Diffuse + | Diffuse + |
| MelanA | Negative | Positive |
| HMB45 | Negative | Positive |
| INI-1 | Lost (~80%) | Retained |
| Molecular | No EWSR1 fusion | EWSR1-ATF1/CREB1 fusion |
MelanA negative + INI-1 loss = EMPNST, not clear cell sarcoma.
So the diagnosis for Q4 remains Epithelioid MPNST - the diffuse S100 is not a contradiction here; it's actually one of EMPNST's defining features that sets it apart from conventional MPNST. As Modern Pathology puts it: "EMPNST is almost always strongly and diffusely positive for S100 protein, in contrast to other types of MPNSTs."
Ini 1 loss tumours
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INI-1 SMARCB1 loss tumors complete list IHC pathology 2024
Here is a comprehensive, organized list of all INI-1 (SMARCB1)-deficient tumors:
INI-1 (SMARCB1) Loss - Complete Tumor List
🔴 ALWAYS/Consistently Lost (defining feature)
| Tumor | Notes |
|---|---|
| Malignant Rhabdoid Tumor (MRT) | Extrarenal / renal - the prototype |
| Atypical Teratoid/Rhabdoid Tumor (AT/RT) | CNS equivalent of MRT |
| Epithelioid Sarcoma (classic & proximal type) | ~90-100% loss; proximal type = rhabdoid morphology |
| Renal Medullary Carcinoma | Young sickle cell trait patients |
| SMARCB1-deficient Sinonasal Carcinoma | Basaloid undifferentiated carcinoma of sinonasal tract |
| Pediatric Chordoma (poorly differentiated) | Especially in children < 5 years |
🟡 FREQUENTLY Lost (~50-80%)
| Tumor | Loss Rate | Notes |
|---|---|---|
| Epithelioid MPNST | ~50-80% | Key differentiator from melanoma/CCS |
| Myoepithelial Carcinoma of soft tissue | ~40-50% | Especially in children |
| Schwannomatosis (germline) | Germline SMARCB1 | Predisposes to multiple schwannomas |
🟢 SOMETIMES Lost (subset)
| Tumor | Loss Rate | Notes |
|---|---|---|
| Synovial Sarcoma | ~30% | Focal/heterogeneous loss |
| Extraskeletal Myxoid Chondrosarcoma | Subset | Especially EWSR1-NR4A3 type |
| Ossifying Fibromyxoid Tumor (malignant) | Subset | |
| Rhabdoid Carcinoma of GI tract | Subset | Poor prognosis |
| GIST | Rare subset | |
| Dedifferentiated Chordoma | Subset |
Key Mnemonics
"REAMS" - the core INI-1 loss tumors:
- R - Rhabdoid tumors (MRT, AT/RT)
- E - Epithelioid Sarcoma
- A - AT/RT
- M - Medullary carcinoma (renal)
- S - Sinonasal SMARCB1-deficient carcinoma
Additional important ones: Epithelioid MPNST, Myoepithelial carcinoma, Synovial sarcoma (subset), Poorly differentiated chordoma (pediatric)
Why Does INI-1 Loss Matter Clinically?
- Diagnostic - helps classify undifferentiated/rhabdoid tumors
- Therapeutic target - EZH2 inhibitor tazemetostat is FDA-approved for epithelioid sarcoma with INI-1 loss
- Germline testing - SMARCB1 germline mutations cause schwannomatosis and familial rhabdoid tumor predisposition syndrome
- Prognostic - INI-1 loss generally confers aggressive behavior
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