This elective pathology review, led by Dr. Jared Gardner, examines ten challenging unknown cases spanning soft tissue and bone pathology. The discussion focuses on identifying characteristic histological features, navigating common differential diagnoses, and utilizing molecular markers for definitive classification of complex tumors. Cases covered include various grades of Myxofibrosarcoma and related fibromyxoid entities, Well-Differentiated Liposarcoma/Atypical Lipomatous Tumor, Epithelioid Sarcoma, and rare neural sheath tumors like Malignant Melanotic Nerve Sheath Tumor (MMNST). Key diagnostic features reviewed include muscle entrapment (Desmoid Fibromatosis), the significance of pleomorphic cells versus pseudo-lipoblasts (Myxofibrosarcoma), and specific markers like INI1 loss (Epithelioid Sarcoma) and PRKAR1A loss (MMNST). The final cases cover classic benign entities, including Schwannoma and the bone tumor Chondroblastoma, emphasizing morphologic pearls for recognition, such as "chicken wire" calcification and a multi-component cellular background in tenosynovial giant cell tumor.
Pathology Case Review: Soft Tissue & Bone Unknowns
0:19 Case 1: Desmoid Fibromatosis (35 y/o female, abdominal nodule)
Key Features: Hypocellular tumor composed of bland fibroblasts/myofibroblasts running in broad, sweeping fascicles. Crucial finding is the entrapment of skeletal muscle (0:41), which can mimic rhabdomyoblasts or pleomorphic change.
Takeaway: This tumor is locally aggressive with a high recurrence rate, but lacks metastatic potential. Driven by nuclear Beta-Catenin buildup (6:07).
7:48 Case 2: Well-Differentiated Liposarcoma (WDL) / Atypical Lipomatous Tumor (ALT) (50 y/o male, 15 cm retroperitoneal mass)
Key Features: The classic triad: mature fat with variable adipocyte size (8:12), abundant sclerotic collagen bands (8:26), and scattered hyperchromatic atypical/pleomorphic cells (8:41), which are often found near blood vessels (14:40).
Takeaway: Location dictates naming (Retroperitoneum = WDL, Extremity = ALT). Confirmation is achieved by finding MDM2 gene amplification (10:47), although characteristic histology alone can be diagnostic in classic cases.
18:05 Case 3: Epithelioid Sarcoma (24 y/o male, hand mass)
Key Features: Epithelioid cells forming nodules with central necrosis (19:31). Cells have pale, vesicular chromatin and dense pink cytoplasm (20:25) due to keratin filaments (20:28), resembling squamous cell carcinoma or rheumatoid nodule.
Takeaway: This aggressive sarcoma of the distal extremity is characterized by the loss of the tumor suppressor protein INI1/SMARCB1 (21:26), which is essential for differential diagnosis.
23:41 Case 4: Myxofibrosarcoma (Grade 1/Low-Grade) (60 y/o male, leg mass)
Key Features: Mixoid background, long curvilinear vessels (25:08), infiltrative growth, and scattered pleomorphic/atypical cells. Pseudo-lipoblasts (27:47) are present—cells that suck up mucin (hyaluronic acid).
Takeaway: MFS is a relatively common sarcoma that is highly infiltrative, leading to a high rate of local recurrence. Must have pleomorphism to distinguish from Low-Grade Fibromyxoid Sarcoma.
29:16 Case 5: Schwannoma (Benign) (20 y/o female, 2 cm neck mass)
Key Features: Encapsulated tumor showing biphasic pattern: hypercellular Antoni A areas with classic Verocay bodies (nuclear palisading) (30:10) and hypocellular Antoni B areas with loose, foamy cells (32:20). Features also include prominent hyalinized sclerosis around vessels (31:34).
Takeaway: A benign neural sheath tumor, usually diffusely positive for S100 and SOX10. The recognition of subtle palisading and hyalinized vessels is crucial for small biopsies.
34:26 Case 6: Low-Grade Fibromyxoid Sarcoma (LGFMS) / Evan's Tumor (42 y/o male, leg mass)
Key Features: Deceptively bland, hypocellular, collagen-rich spindle cell tumor lacking significant atypia, necrosis, or high mitotic rate. Demonstrates characteristic variability between hypocellular sclerotic/collagenous areas and mildly cellular mixoid areas (37:04).
Takeaway: LGFMS is malignant despite its benign appearance. It is diagnosed via its characteristic histology combined with strong positivity for MUC4 (37:25) and/or the FUS-CREB3L fusion.
Key Features: Tumor arising from a nerve root (38:47), composed of highly atypical epithelioid/spindle cells with prominent nucleoli and abundant melanin pigment (39:41). Frequently features Samoma bodies (laminated calcifications) (44:56).
Takeaway: A rare, aggressive tumor (metastatic risk 15-45%) that mimics metastatic melanoma but has a neural origin. Molecularly confirmed by the loss of PRKAR1A (42:56).
Key Features: Sheets of uniform mononuclear chondroblasts with characteristic nuclear grooves (coffee bean/reniform nuclei) (50:06), interspersed with giant cells. Definitive feature is the presence of the purple, "chicken wire" calcification (50:47).
Takeaway: A benign tumor classically found in the epiphysis of skeletally immature patients. Must be differentiated from Giant Cell Tumor of Bone.
Key Features: Circumscribed nodule (58:40), abundant foamy histiocytes (xanthoma cells), scattered osteoclastic giant cells, and hemosiderin deposition. The neoplastic cells are plump plasmacytoid histiocytes, often exhibiting a peripheral "halo" or ring of hemosiderin (1:00:27). High mitotic activity can be alarming (1:03:31).
Takeaway: A common, locally problematic benign tumor that can be metabolically active (PET avid) and may mimic malignancy on small biopsies if giant cells are sparse.
1:07:37 Case 10: Myxofibrosarcoma (High Grade / Grade 3) (40 y/o male, leg mass in skin/subcutis)
Key Features: Tumor is heterogeneous (hypocellular mixoid areas and solid sheets of highly cellular pleomorphic spindle cells) (1:08:44). Presence of long, curvilinear vessels and tumor necrosis (1:09:47).
Takeaway: The high-grade component consists of sheets of undifferentiated pleomorphic sarcoma (UPS)-like cells. Because MFS is highly infiltrative along subcutaneous septa and fascia, adequate surgical margin clearance is notoriously difficult, leading to a high local recurrence rate and increased risk of metastasis (1:14:01).