Dr. Jarrod Gardner presents a comprehensive review of bone and soft tissue pathology, covering 21 distinct cases with clinical, radiographic, and microscopic correlations. The review focuses on classic features essential for differential diagnosis in a pathology course setting. Key bone tumors discussed include the osteoid-producing malignancies (osteosarcoma) and benign lesions (osteochondroma, osteoid osteoma), as well as the distinction between Giant Cell Tumor of Bone and Aneurysmal Bone Cysts. The soft tissue section examines a spectrum of entities, ranging from benign tumors (Angiolipoma, Schwannoma, Nodular/Proliferative Fasciitis, Spindle Cell Lipoma, Granular Cell Tumor) to highly aggressive high-grade sarcomas (Undifferentiated Pleomorphic Sarcoma, Pleomorphic Liposarcoma, Desmoplastic Small Round Cell Tumor). A strong emphasis is placed on diagnostic immunohistochemistry (IHC) and molecular findings, particularly the role of specific markers like Brachyury (Chordoma), STAT6 (Solitary Fibrous Tumor), and INI1 loss (Epithelioid Sarcoma) for precise classification.
Pathology Review Course: Bone and Soft Tissue Cases
0:14 – Osteosarcoma (Case 1): Classic presentation involves mixed lytic/sclerotic components, soft tissue invasion with hazy mineralization, and periosteal elevation forming Codman’s Triangle (0:22). Key microscopic feature is the production of malignant osteoid/woven bone by atypical, pleomorphic spindle cells (2:00).
Takeaway: Chondroblastic variants must be distinguished from chondrosarcoma, especially in young patients (3:58). Associated genetics include RB and p53 gene abnormalities (4:31).
0:55 – Osteochondroma (Case 2): Radiographically, these appear as exophytic polyps/mushrooms, with the stalk pointing away from the joint (5:32). Microscopically, they feature a hyaline cartilage cap (usually <1 cm) transitioning into bone via endochondral ossification (7:32).
Takeaway: The marrow space of the lesion is contiguous with the medulla of the underlying bone (7:58). Associated with EXT1 and EXT2 genes (6:39).
10:11 – Osteoid Osteoma (Case 3): Characterized radiographically by a tiny, radiolucent nidus surrounded by dense, reactive sclerotic bone (10:47). Clinically defined by pain that is worse at night and relieved by aspirin/NSAIDs (11:32). Microscopically, bland osteoblasts lay down highly organized woven osteoid (12:45).
Detail: Osteoblastoma is similar but larger (>1 cm) (14:04).
15:36 – Giant Cell Tumor of Bone (GCTB) (Case 4): Arises characteristically in the epiphysis (end of long bone) (15:56), presenting as a lytic lesion (16:02). Microscopically defined by sheets of very large, multinucleated osteoclast-like giant cells interspersed with uniform, oval stromal cells that have nuclei similar to those of the giant cells (17:40).
20:58 – Angiolipoma (Case 5): Classic presentation is a painful, multiple subcutaneous nodule (often forearm) in adult women (21:06). Key features include mature fat, clustered small capillaries, and characteristically, fibrin thrombi within the vessel lumens (22:54).
23:49 – Angiomyofibroblastoma (Case 6): Typically found in the vulva/genital tract. Features plump, eosinophilic epithelioid/spindle cells arranged in cords and chains, often swirling around dilated, ectatic blood vessels (25:00).
IHC: Positive for Desmin, Estrogen Receptor (ER), and Progesterone Receptor (PR) (25:38).
26:02 – Chordoma (Case 7): Most commonly arises at the ends of the spine (clivus or sacrum) (26:12). Key features include cords and chains of epithelioid cells in an abundant mixoid (blue) background (26:53). The classic cell type is the physaliferous cell (multi-vacuolated/bubbly cytoplasm) (29:23).
IHC/Molecular: Positive for Keratin/EMA/S100. Diagnosis confirmed by nuclear positivity for Brachyury (28:32).
30:32 – Schwannoma (Case 8): Well-circumscribed, encapsulated tumor (31:09). Shows alternating hypercellular (Antoni A) and hypocellular/edematous (Antoni B) areas (31:40). Other clues: thick-walled, sclerotic vessels, hemorrhage, and scattered pleomorphism (which is benign in this context) (33:04).
35:00 – Undifferentiated Pleomorphic Sarcoma (UPS) (Case 9): Presents as a large, deep mass (e.g., thigh) in older adults (35:14). Defined by sheets of highly pleomorphic, bizarre, hyperchromatic cells (35:25).
Takeaway: UPS is a diagnosis of exclusion (37:01), lacking any specific line of differentiation (37:40). Pleomorphism suggests aneuploidy, often ruling out translocation sarcomas (38:46).
39:27 – Solitary Fibrous Tumor (SFT) (Case 10): Shows a "patternless pattern" of bland spindle cells (42:51) with variable cellularity and hyalinized/sclerotic zones (40:48). Characterized by dilated, branching staghorn vessels (hemangiopericytoma-like pattern) (39:54).
IHC/Molecular: Historically CD34 positive (43:25). Currently diagnosed using the highly specific nuclear stain STAT6 (44:21), reflecting the NAB2-STAT6 translocation.
44:54 – Epithelioid Sarcoma (Case 11): Typically arises in the distal extremities (acral sites) (45:01). Presents as multiple nodules in the dermis/subcutis (45:18). Cells are epithelioid with dense pink/abundant cytoplasm and vesicular chromatin (47:25). Can mimic deep granuloma (45:35).
IHC/Molecular: Keratin and EMA positive (46:39). Definitive diagnosis relies on nuclear loss of INI1/SMARCB1 (48:30). Aggressive; notable for metastasizing to lymph nodes (49:42).
50:00 – Nodular Fasciitis (Case 12): Benign lesion of plump myofibroblasts (50:20), often rapid growth/small size (<3 cm). Microscopic features: loose, mixoid background, prominent mitosis (benign), and focal cystic degeneration (50:58). Cells often adopt a loose, "feathery" or "tissue culture" arrangement (52:45).
54:40 – Proliferative Fasciitis (Case 13): A variant of nodular fasciitis, often arising near the fascia (55:06). Diagnostic feature is the presence of scattered, large, scary-looking ganglion-like cells (plump, round nuclei with prominent nucleoli) within the classic nodular fasciitis background (55:54). Must be recognized as benign despite cellular atypia (56:43).
58:02 – Aneurysmal Bone Cyst (ABC) (Case 14): Presents as a multiloculated, balloon-like lytic lesion in young patients (58:40). Microscopically, it features blood-filled cystic spaces separated by septa composed of loose fibrous tissue (fasciitis-like), woven bone (osteoid), and pockets of osteoclast-like giant cells (1:02:22).
Takeaway: Distinguished from GCTB by the vast majority of the lesion being cystic/fibrous, not sheets of giant cells (1:02:59). Associated with USP6 gene fusion (58:26).
1:04:35 – Plantar Fibromatosis (Case 15): Arises from the tendon/fascia of the plantar foot (1:04:40). Characterized by broad, sweeping fascicles of bland, cellular fibroblasts/myofibroblasts (1:04:54).
Detail: Unlike Palmar fibromatosis (Dupuytren’s), the plantar form is usually larger and more cellular (1:06:46). Classically associated with nuclear expression of Beta-catenin (1:07:29).
1:09:00 – Pleomorphic Liposarcoma (PLS) (Case 16): High-grade sarcoma (1:09:47) defined by the presence of diagnostic pleomorphic lipoblasts—bizarre cells containing sharp, clear, large vacuoles that indent the hyperchromatic nucleus (1:09:07).
Takeaway: PLS often exhibits the wildest atypia among human malignancies (1:11:06). Must be differentiated from D-DIF Liposarcoma, which usually lacks lipoblasts (1:09:57).
1:13:00 – Granular Cell Tumor (Case 17): Common sites include the tongue and anogenital region (1:15:10). Features a syncytial sheet of cells with abundant granular eosinophilic cytoplasm (due to phagolysosomes) and small, round nuclei (1:13:37). May contain Pustulo-ovoid bodies (1:13:22).
IHC/Clinical: S100 and CD68 positive (1:14:42). Crucially, can cause pseudoepitheliomatous hyperplasia (PEH) of the overlying epithelium, potentially mimicking squamous cell carcinoma (1:15:38). Perineural involvement is common and benign (1:16:48).
1:17:47 – Desmoplastic Small Round Cell Tumor (DSRCT) (Case 18): Highly aggressive tumor typically found in the abdominal/pelvic cavity of young males (1:18:55). Defined by small round blue cells arranged in nests/islands surrounded by dense, desmoplastic stroma (1:18:35).
IHC/Molecular: Co-expresses Keratin/EMA + Desmin (1:19:51). Nuclear WT1 (C-terminus specific) is positive (1:20:17). Caused by the EWS-WT1 gene fusion (1:21:51).
1:23:32 – Synovial Chondromatosis (Case 19): Metaplastic process resulting in multiple, irregular islands/nodules of hyaline cartilage directly adjacent to a synovial-lined space (1:24:06). Chondrocytes often show a characteristic clustering or "cloning" (1:24:54).
1:26:32 – Plexiform Neurofibroma (Case 20): Associated with NF1 (1:26:37). Characterized microscopically by distended, massively expanded nerves showing multiple cross-sections (the "bag of worms" grossly) (1:27:47).
Crucial Takeaway: Diagnosing Plexiform NF is equivalent to labeling the patient with NF1, a major clinical diagnosis (1:28:19).
1:30:00 – Spindle Cell Lipoma (Case 21): Usually arises in the posterior neck/upper back of older men (1:30:09). Composed of mature fat, bland spindle cells that often show subtle palisading (1:33:03), ropey collagen bundles (1:31:04), and a variable mixoid background (1:31:07).
Molecular: Often shows loss of chromosome 13q/16q, resulting in nuclear loss of the RB1 protein (1:32:16).
IHC: CD34 positive (1:34:09), S100 negative in spindle cells (1:34:31).