Dr. Jared Gardner conducts an interactive grand rounds session with UNC pathology residents, reviewing seven complex and often misdiagnosed spindle cell and soft tissue tumor cases, emphasizing challenging differential diagnoses and key diagnostic features. The presentation covers treacherous melanomas (desmoplastic and spindle cell types), a rare mycobacterial spindle cell pseudotumor mimicking a fibrohistiocytic lesion, and several rare sarcomas including Mixoinflammatory Fibroblastic Sarcoma, Mesenchymal Chondrosarcoma, and a large Dedifferentiated Chondrosarcoma with an osteosarcomatous component. Dr. Gardner uses architectural patterns, cellular features (including atypical giant nucleoli and pseudo-Touton cells), clinical context (age, location), and immunohistochemical findings (S100/SOX10 positivity, Mart-1 negativity in desmoplastic variants) to navigate these difficult cases. The session concludes with career advice for residents interested in competitive subspecialties like dermatopathology and soft tissue pathology.
Summary of Soft Tissue Pathology Unknowns
0:38 Case 1: Desmoplastic Melanoma (DM): Presents in an 80 y/o man as a firm, scar-like plaque on the sun-damaged scalp. Key features include a hypocellular, neural/fibroblastic pattern of spindled cells separated by abundant collagen (desmoplasia). The tumor often invades deeply (e.g., down to fascia/galea, 0:55) and is characterized by lymphocyte aggregates (4:01) and perineural invasion (5:42). DM is usually negative for standard melanoma markers (Mart-1/HMB-45) but positive for S100 and SOX10 (6:45). Pure DM has a better prognosis but is locally aggressive.
11:41 Case 2: Spindle Cell Melanoma: A rapidly growing, ulcerated black nodule in a 65 y/o man. This is a high-grade malignancy composed of cellular, pleomorphic spindle cells often arranged in fascicles (16:29), with significant atypia and necrosis (12:15). Unlike DM, it is highly cellular. This type of melanoma can be amelanotic and must be differentiated from Atypical Fibroxanthoma (AFX), Pleomorphic Dermal Sarcoma, and Spindle Cell Squamous Cell Carcinoma using IHC (S100/SOX10).
21:26 Case 3: Mycobacterial Spindle Cell Pseudotumor: A skin-colored nodule in an older woman, clinically mistaken for a cyst. Histologically, it features spindled cells, abundant lymphocytes, and giant cells resembling Touton cells (24:25). The key diagnostic feature is the presence of numerous Acid-Fast Bacilli (AFB) visible within foamy cells (27:27). The organisms were so numerous they were also PAS positive (27:30, 30:46). This entity is usually seen in immunosuppressed patients and mimics a tumor (pseudotumor).
38:18 Case 4: Mixoinflammatory Fibroblastic Sarcoma (MIFS): A subcutaneous nodule in a 40 y/o man. Diagnostic features include a mixoid background, a dense inflammatory infiltrate (often eosinophils/plasma cells), and highly atypical, pleomorphic spindle cells with characteristic Reed-Sternberg-like features (39:54) and giant, CMV viral inclusion-like nucleoli (40:02, 40:29). Location is typically the distal extremities (hand/foot). The tumor tends to recur locally but rarely metastasizes.
43:35 Case 5: Calcifying Aponeurotic Fibroma: Presents in a 10 y/o boy on the hand (a classic location). The lesion is characterized by islands of calcification and chondroid metaplasia, surrounded by small round cells exhibiting palisading (44:06), which transition into thin fascicles of bland fibroblasts. Although benign, it has a tendency for local recurrence.
48:30 Case 6: Mesenchymal Chondrosarcoma: An intramuscular thigh mass in a 30 y/o woman. This sarcoma is biphasic: islands of wispy, hyaline cartilage juxtaposed with sheets of monotonous small round blue cells (50:39). The round cell component typically displays a staghorn (hemangioperiocytic) vascular pattern (52:00). It is associated with the HEY1-NCOA2 gene fusion (51:29) and can be a diagnostic pitfall due to shared IHC positivity with Ewing sarcoma and sometimes rhabdomyosarcoma.
56:00 Case 7: Dedifferentiated Chondrosarcoma: A large, destructive pelvic bone mass in a 60 y/o man. The tumor shows an aggressive component of high-grade pleomorphic spindle cells (1:02:07) making osteoid—a heterologous osteosarcomatous component (1:04:04)—in addition to the underlying chondrosarcoma component (1:01:50). A key sign of malignancy is the permeative growth pattern (1:00:50), where tumor surrounds pre-existing lamellar bone. D-diff chondrosarcoma carries a very poor prognosis and is primarily treated surgically.
1:08:03 Key Takeaway (Career Advice): For residents interested in Derm Path or Soft Tissue, Dr. Gardner recommends early research involvement, away rotations at fellowship centers, showing strong organization, and using social media (like Twitter) for networking and demonstrating engagement, especially as fellowship applications occur early in residency.