Dr. Jared Gardner presents eight unknown pathology cases to Yale pathology residents, focusing primarily on challenging benign and locally aggressive soft tissue tumors and two classic benign bone tumors. The presentation serves as a teaching session on differential diagnosis, nuanced histological features, and the application of immunohistochemical and molecular markers. Key soft tissue entities discussed include Deep Angiomyxoma, Cellular Angiofibroma, Mammary Type Myofibroblastoma, and Superficial Acral Fibromyxoma—entities frequently linked by RB1 loss. The session also contrasts the distinction between Cellular Dermatofibroma and Dermatofibrosarcoma Protuberans (DFSP), highlighting a difficult case of DFSP mimicking Solitary Fibrous Tumor. Finally, two characteristic benign bone lesions—Chondroblastoma (epiphyseal, chicken wire calcification) and Chondromyxoid Fibroma (metaphyseal, pseudo-lobulation)—are reviewed with an emphasis on radiographic and histological correlation.
Summary of Pathology Cases
0:38 | Case 1: Deep Angiomyxoma (formerly Aggressive Angiomyxoma)
Details: Large (15 cm) mass in the vulvar/pelvic soft tissue of a 35-year-old woman.
Key Features: Hypocellular, prominent vessels (ranging from small to large, thick-walled), pale, edematous background (not typically "blue mixoid"), fine collagen wisps, and subtle bundles of pink spindle cells (smooth muscle) swirling from vessels.
Takeaway: "Aggressive" refers to the tumor's size and high recurrence risk due to difficult, infiltrative surgical margins, not malignant behavior. Positive for Desmin, ER, and PR, with a subset showing HMGA2 rearrangements.
11:06 | Case 2: Cellular Angiofibroma (of the genitals)
Details: 50-year-old man with a 2 cm inguinal mass.
Key Features: Bland spindle cells in a dense, ropey (wavy/“ramen noodle”) collagen background, staghorn/ectatic vessels mimicking SFT, subtle nuclear palisading/packeting, and frequent scattered mast cells. Often contains fat.
Takeaway: Part of the Spindle Cell Lipoma (SCL) family. Immunostains usually show CD34 positivity and RB1 loss (useful for separating from STAT6+ SFT). Benign, cured by simple excision.
Key Features: Well-circumscribed lesion composed of thick, coarse ropey collagen bundles interspersed with fascicles of bland spindle cells showing a characteristic "zigzagging" pattern.
Takeaway: Another entity in the RB1 loss group with overlap to SCL/Cellular Angiofibroma. It is typically CD34+ and uniquely often Desmin+ (co-expression is key). Occurs in both men and women, often outside the breast (hence "mammary type"). Benign.
23:36 | Case 4: Superficial Acral Fibromyxoma (Digital Fibromyxoma)
Details: Periungual papule on the finger of a 40-year-old man.
Key Features: Poorly circumscribed, mixoid, with a swirling/whirling pattern of CD34+ spindle cells, and an increased vascular network. Can infiltrate fat and mimic DFSP.
Takeaway: Distinguished from DFSP by absence of the COL1A1-PDGFB fusion and the presence of RB1 loss. Requires complete excision, as recurrence is common on acral surfaces due to conservative surgical approach.
31:01 | Case 5: Cellular Dermatofibroma (Fibrous Histiocytoma)
Details: Back nodule in a 30-year-old woman (clinical history often "cyst").
Key Features: Deep lesion extending into the subcutis, showing a cellular, storiform pattern. Cells are plump and more atypical than DFSP cells. Key differentiating clues include the presence of multinucleated giant cells (histiocytes), foamy cells, hemorrhage/hemosiderin, and fat necrosis at the edges (suggests DF, not DFSP).
Takeaway: Must be distinguished from DFSP, which is CD34+. DF is typically CD34- (central portion). Cellular DF can locally persist/recur due to deep extension and often partial sampling, but metastasis is extremely rare.
44:07 | Case 6: Dermatofibrosarcoma Protuberans (DFSP) with Fibrosarcomatous Transformation
Details: Large scalp mass in a 30-year-old woman.
Key Features: Highly challenging case due to extremely prominent staghorn/hemangiopericytoma-like vessels (mimicking SFT) and minimal fat entrapment. Diagnosis confirmed by the classic storiform (pinwheel) growth pattern and very bland CD34+ cells.
Transformation: Cellular areas showing longer, intersecting fascicles in a "herringbone" pattern confirm fibrosarcomatous transformation.
Takeaway: DFSP requires FISH testing to confirm translocation if SFT (STAT6+) is in the DDx. DFSP is locally aggressive and often recurs, especially on the scalp, requiring large surgeries. Fibrosarcomatous transformation increases the already low metastatic risk (from ~2% to ~15%).
Details: 20-year-old man with a lytic lesion in the proximal tibia metaphysis.
Key Features: Metaphyseal location. Highly mixoid/chondroid matrix (looks more mixoid than cartilage). Cells are spindle to stellate, often described as triangle-shaped ("pennant flags"). Lesion exhibits pseudo-lobulation (hypocellular centers with more compressed, cellular periphery).
Takeaway: Benign and rare. Cytology can sometimes show scattered pleomorphism, which is benign in this context. Requires strong correlation with radiology.