This is certainly a challenging case. Let's go through the findings step-by-step to help frame the differential diagnosis and the appropriate next steps in the workup.
Key Findings:
- Patient profile: 55-year-old male with a smoking history and a large aggressive mediastinal mass extending into the lungs.
- Cytology: The cells are discohesive with rhabdoid features and pleomorphism, but without squamous or glandular differentiation.
- Immunohistochemistry results:
- Negative for: Keratins (very rare staining), S100, CD45, TTF-1, p40, Desmin, ERG, CD31, OCT3/4, CD30, CD15, SOX10.
- Positive for: CD34 and SALL4.
Initial Interpretation:
- Rhabdoid Features: The rhabdoid morphology suggests that this could be a high-grade malignant tumor with undifferentiated features. Rhabdoid cells often evoke concern for high-grade malignancies such as epithelioid sarcomas, rhabdoid tumors, or undifferentiated carcinomas.
- Negative Keratin and Lineage Markers: The absence of keratin (with only very rare staining) and other epithelial markers (e.g., TTF-1, p40) suggests that this is likely not a carcinoma. The negativity for mesenchymal markers (Desmin, SOX10) also makes certain sarcomas less likely.
- Positive for CD34 and SALL4: These markers are key.
- CD34 positivity is often seen in vascular tumors (e.g., angiosarcomas), soft tissue tumors (e.g., solitary fibrous tumors), or hematopoietic tumors.
- SALL4 is a marker of germ cell tumors (specifically yolk sac tumors or other non-seminomatous tumors) but can also be expressed in some undifferentiated malignancies. The negative OCT3/4 and SOX10 rule out a classic seminoma, but SALL4 points us toward a possible extragonadal germ cell tumor (EGGCT).
Working Hypothesis:
Given the mediastinal location (a common site for extragonadal germ cell tumors in adults), the SALL4 positivity, and CD34 expression, this could represent a poorly differentiated or non-seminomatous germ cell tumor, possibly with a yolk sac tumor component. The lack of squamous, glandular, or clear sarcomatous differentiation helps narrow the diagnosis to an undifferentiated form of germ cell tumor.
Next Steps in Workup:
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Serum Markers:
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AFP (Alpha-fetoprotein) and beta-hCG (human chorionic gonadotropin) should be ordered. These are critical markers for yolk sac tumors and choriocarcinoma, respectively. Elevated levels would support a diagnosis of a germ cell tumor.
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Further IHC:
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Consider additional markers like Glypican-3, which can support the diagnosis of a yolk sac tumor.
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PLAP (Placental alkaline phosphatase) could be ordered, although it's more common in seminomas and embryonal carcinomas, which seem less likely here.
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Molecular Studies: If the diagnosis remains unclear, molecular testing to identify characteristic mutations or chromosomal alterations (e.g., 12p amplification, often seen in germ cell tumors) could be helpful.
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Radiology Correlation: Imaging of the testicles should be considered to rule out a primary gonadal germ cell tumor with metastasis, although the mediastinal mass in isolation strongly suggests an extragonadal germ cell tumor.
Final Differential Diagnosis:
- Extragonadal Germ Cell Tumor (likely with a yolk sac component given the SALL4 positivity and morphology).
- Solitary Fibrous Tumor with aberrant expression of SALL4 (less likely, but CD34 positivity warrants consideration).
- Undifferentiated Sarcoma or Dedifferentiated Tumor with aberrant marker expression (unlikely given the strong SALL4 positivity).