July 2020*

A 50-year-old male with no significant past medical history, who presented with generalized weakness, cough, and upper back pain.

Contributors: 

Jaffar Khan, MBBS

PGY-2 Resident Physician, Anatomic Pathology and Clinical Pathology

Department of Clinical Pathology & Laboratory Medicine

Indiana University School of Medicine

Sheila E Segura, MD

Assistant Professor, Department of Pathology and Laboratory Medicine

Indiana University School of Medicine

*This case has been peer reviewed

Clinical history: 

We describe a case of 50-year-old male with no significant past medical history, who presented with generalized weakness, cough, and upper back pain. Imaging revealed bilateral lung nodules, mediastinal lymphadenopathy, lytic bone lesions, and multiple liver lesions concerning for metastatic disease. A chest CT showed a 7.9 cm right upper lobe mass with infiltration into the mediastinum, compatible with a clinical impression of metastatic lung cancer. An US-guided fine needle aspiration of the liver lesion was performed.

Microscopic examination and immunohistochemistry: 

The Diff-Quik and Pap stained slides (figures 1&2) displayed large cohesive sheets, clusters and loosely cohesive groups of small, highly atypical epithelioid cells. The cells showed high nuclear to cytoplasmic ratio, scant cytoplasm, enlarged nuclei with focal nuclear molding and granular chromatin. Scattered mitotic figures and increased apoptosis were also noted. The cytomorphologic findings were compatible with a small cell carcinoma; however, initial immunohistochemical workup showed that the tumor was negative for CAM 5.2, CK AE1/AE3, CK5/6, p40, TTF-1, synaptophysin and chromogranin. On additional immunohistochemical stains, the tumor was positive for SOX10, S100 and CD56 (focal), while negative for keratin cocktail, HMB45, Melan-A, MITF, tyrosinase, LCA and PAX-5. The Ki67 labelling index was approximately 30%. The immunohistochemical profile was consistent with metastatic melanoma. Subsequent molecular testing showed BRAF V600E mutation in the tumor cells, further supporting the diagnosis of metastatic melanoma

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Fig. 1. Diff-Quik shows single and loose cohesive clusters of cells with scant cytoplasm and nuclear molding.

 Fig. 1                

Fig.2. PAP stained slide. Cells with scant cytoplasm, enlarged nuclei and granular chromatin are noted. Apoptotic bodies are also seen.

 Fig. 2

Fig. 3. H&E section shows loose clusters of tumor cells with scant cytoplasm, nuclear molding, stippled chromatin, scattered mitotic figures and apoptotic bodies.    

 Fig. 3

Fig.4:  S100  

Fig.  4

Fig. 5: Sox 10

 Fig. 5

Fig. 6: CD56

Fig. 6

July 2020 Final Diagnosis and Discussion