Slide 3 — Case 1877/26 H1

Gross Appearance (expected)

Histological Description

• Architecture: A cystic structure with a well-defined fibrous wall. No true epithelial lining is present (this is a pseudocyst - no synovial lining).
• Cyst wall: Composed of dense, acellular to hypocellular fibrous (collagenous) connective tissue arranged in whorled bundles.
• Luminal surface: Lined by flattened to spindle-shaped fibroblasts/myofibroblasts; no cuboidal or columnar epithelium.
• Cyst contents: Central pool of myxoid/mucinous material rich in hyaluronic acid and glycosaminoglycans (pale, basophilic on H&E).
• Surrounding tissue: No inflammatory infiltrate, no mitoses, no nuclear atypia. Fibrovascular septa may partition the cavity into lobules.
• Special stains: Alcian blue/PAS positivity of cyst contents confirming mucopolysaccharide-rich fluid.

Diagnosis

Key Teaching Points

• Most common soft tissue "cyst" around joints and tendons; popliteal fossa is a classical location (Baker's cyst is a related bursal cyst connected to joint space - distinguish on clinical/gross grounds).
• The absence of a true synovial lining is the key histological feature distinguishing a ganglion from a true synovial cyst.
• Pathogenesis: myxoid degeneration of connective tissue, not herniation of synovium.
• Differential: Baker's cyst (has synovial lining + communicates with joint), lipoma, schwannoma (look for S100+ spindle cells with Verocay bodies).

Slide 4 — Case 2820/26 V

Important note on bilaterality:

• Bilateral in ~20% of benign serous cystadenomas, ~30% of borderline serous tumors, ~66% of serous carcinomas
• Mucinous tumors are bilateral in only 5% - bilaterality strongly favors serous type

Scenario A: Benign Serous Cystadenoma

• Cyst lining: Single layer of columnar to cuboidal epithelial cells with abundant cilia (tubal-type epithelium).
• Papillae: Delicate fibrovascular papillary projections covered by single layer of bland columnar epithelium with cilia.
• No stratification, no atypia, no stromal invasion.
• Psammoma bodies: Concentric, laminated calcifications may be present (not specific for malignancy, but characteristic of serous tumors).
• Stroma: Loose fibrous stroma with thin-walled blood vessels; no desmoplasia.
• No mitotic figures in benign lesions.

Scenario B: Borderline Serous Tumor (if increased complexity)

• Increased complexity and branching of papillae (hierarchical branching).
• Epithelial stratification (2-3 cell layers) and tufting.
• Mild to moderate nuclear atypia but NO stromal invasion.
• Detached epithelial cell clusters ("epithelial budding") floating freely in cyst lumen.
• Micropapillary pattern may be present.

Scenario C: Mucinous Cystadenoma (if unilateral and mucin-filled)

• Cyst lining: Single layer of tall, columnar cells with basally placed nuclei and apical mucin vacuoles (goblet cell type - intestinal differentiation, OR endocervical type).
• No cilia (key distinction from serous type).
• Mucin-filled glandular spaces.
• Thin fibrous septa separating locules.
• No nuclear atypia, no mitoses, no stromal invasion in benign variety.
• Borderline mucinous tumor shows: epithelial stratification, papillary/villous intraglandular growth resembling intestinal adenoma, mild atypia - but NO stromal invasion.

Probable Diagnosis for Discussion

Slide 5 — Case 2037/26 A

Gross Appearance (expected)

Histological Description

• Distended appendiceal lumen.
• All layers of the wall are visible: mucosa, submucosa, muscularis propria, serosa.
• Diffuse neutrophilic infiltration visible at low power (key hallmark).

• Mucosa: Ulceration of surface epithelium; crypts show neutrophilic infiltration (crypt abscesses). Goblet cells may be depleted. Lymphoid hyperplasia in submucosa.
• Submucosa: Edema, vascular congestion, neutrophilic infiltration, fibrin exudation.
• Muscularis propria: Neutrophilic infiltration of the muscle coat - this is the diagnostic criterion for acute appendicitis (neutrophils must extend into muscularis to confirm diagnosis).
• Serosa / periappendiceal fat: Fibrinopurulent exudate on the serosal surface; vascular congestion; perivascular neutrophilic cuffing. Reactive mesothelial cells may be present.

• Gangrenous appendicitis: Transmural necrosis, vascular thrombosis, hemorrhage, complete loss of mucosal architecture.
• Periappendicitis: Serosal inflammation in absence of mucosal disease (suggests extrinsic cause, e.g., salpingitis, Crohn's).
• Fecalith may be visible in the lumen.
• Lymphoid follicles in submucosa (may be the initiating obstruction cause in young adults).

Diagnosis

Key Teaching Points

• Diagnostic criterion: Neutrophilic infiltration of the muscularis propria. Neutrophils in mucosa alone = not sufficient for diagnosis.
• Etiology: Luminal obstruction (fecalith, lymphoid hyperplasia, parasite, foreign body) → bacterial overgrowth → inflammation → ischemia → necrosis.
• Most common organisms: E. coli, Bacteroides, Enterococcus (mixed flora).
• Emergency appendicectomy prevents progression to perforation and peritonitis.
• Differential histologically: Crohn's disease (granulomas, skip lesions), carcinoid tumor (check tip of appendix - nests of uniform cells in lamina propria/submucosa).

Summary Table

• IMG_3234 (high power): Intersecting fascicles of spindle cells with elongated, blunt-ended ("cigar-shaped") nuclei, abundant eosinophilic cytoplasm - strongly suggests smooth muscle differentiation
• IMG_3237 (medium power): Dense spindle/fibroblastic cells, prominent thin-walled vasculature, mixed inflammatory infiltrate, fibrous capsule at periphery
• IMG_3236 (medium power): Prominent thick-walled central arteriole with concentric wall, dense lymphoid cells surrounding it - resembles PALS of spleen or Castleman-type hyaline vascular changes
• IMG_3235 (high power): Bland spindle cells in collagenous-to-myxoid stroma, chronic inflammatory infiltrate, no atypia/necrosis - nodular fasciitis / IMT / organizing chronic inflammation

• Case: 1877/26 H1 | 60/F | Popliteal fossa subcutaneous swelling
• The combination of: (1) a thick-walled, hyalinized vessel, (2) dense lymphoid infiltrate around it, (3) fascicles of spindle cells with smooth muscle-type nuclei, (4) fibrous capsule, (5) subcutaneous popliteal fossa location in a 60-year-old female is most consistent with a Schwannoma OR a Leiomyoma/Smooth muscle tumor of soft tissue, OR given the vascular-lymphoid pattern in IMG_3236, a Castleman Disease (Hyaline Vascular type) or a fibromatosis/nodular fasciitis.

SLIDE 3 — CASE 1877/26 H1

HISTOLOGICAL DESCRIPTION

Low Power Scan (Architectural Pattern):

Medium Power (IMG_3237):

• A thin, well-formed fibrous capsule is seen at the periphery.
• The main lesion consists of densely packed spindle/fusiform cells with a fascicular arrangement.
• Numerous thick-walled blood vessels are distributed throughout the stroma - this is a key feature; the vessel walls are thickened and composed of smooth muscle coats (IMG_3236 shows a prominent central arteriole with concentric smooth muscle hypertrophy and a perivascular retraction halo - processing artifact).
• The vascular channels vary from small capillaries to medium-sized arterioles.
• A mixed inflammatory infiltrate (predominantly lymphocytes and plasma cells) is seen scattered between the fascicles.
• Stroma is collagenous and fibrillar.

High Power (IMG_3234 & IMG_3235):

• Spindle cells: Elongated, plump, fusiform cells with blunt-ended, "cigar-shaped" nuclei - the hallmark of smooth muscle differentiation.
• Nuclei are vesicular, with finely granular chromatin and small inconspicuous nucleoli.
• No significant nuclear pleomorphism or hyperchromasia.
• Cytoplasm is abundant, deeply eosinophilic (pink), and fibrillar with indistinct cell borders - characteristic of smooth muscle cells.
• In some areas (IMG_3235), the cells are set in a loosely collagenous to focally myxoid stroma with interspersed chronic inflammatory cells (lymphocytes and plasma cells).
• No mitotic figures, no atypical mitoses, no necrosis in the sections examined.

Summary of Key Histological Features:

DIAGNOSIS

Angioleiomyoma (Vascular Leiomyoma)

DETAILED DIAGNOSIS JUSTIFICATION

DIFFERENTIAL DIAGNOSES (for discussion)

1. Leiomyoma (non-vascular type) - lacks the prominent vascular component; fewer vessels
2. Schwannoma - S100+; Antoni A/B areas; Verocay bodies; wavy "buckled" nuclei (NOT blunt-ended) - not seen here
3. Nodular Fasciitis - reactive, NOT encapsulated; looser myxoid stroma; more mitoses; short clinical history
4. Fibromatosis (Desmoid) - bland fibroblasts in dense collagen; NO smooth muscle nuclei
5. Leiomyosarcoma - EXCLUDED: no atypia, no necrosis, no mitoses (>10/10 HPF)
6. GIST - rare in subcutaneous tissue; CD117/DOG-1 positive; different nuclear morphology

KEY TEACHING POINTS FOR MD DISCUSSION

• Angioleiomyoma is one of the most common benign soft tissue tumors of the extremities (lower limb > upper limb), particularly in the subcutaneous popliteal fossa, ankle, and calf.
• Peak incidence: 40-60 year old women - this case is textbook.
• Three histological subtypes: Solid type (compact smooth muscle bundles, few vessels), Cavernous type (large dilated vessels with thin walls), Venous type (thick-walled vessels + smooth muscle bundles) - the venous type is most common.
• IHC: Positive for SMA (smooth muscle actin), Desmin, h-caldesmon - smooth muscle markers. Negative for S100 (excludes schwannoma), CD34 (excludes solitary fibrous tumor).
• Benign behavior: Simple excision is curative. Recurrence is rare.
• The blunt-ended (cigar-shaped) nucleus with deep eosinophilic fibrillar cytoplasm = the single most important diagnostic clue for smooth muscle lineage on H&E.

Ancillary tests to suggest in discussion: SMA immunohistochemistry (expected strongly positive), Desmin (positive), S100 (negative - to exclude schwannoma). Masson's trichrome can highlight muscle vs collagen if needed.

MD Pathology Viva — Case 3 (Angioleiomyoma)

SECTION 1: OPENING / SLIDE DESCRIPTION

"The section shows a well-circumscribed, encapsulated soft tissue lesion composed of interlacing fascicles of spindle cells with blunt-ended, cigar-shaped nuclei and abundant deeply eosinophilic fibrillar cytoplasm, consistent with smooth muscle differentiation. Prominent thick-walled blood vessels are distributed throughout the tumor. No nuclear atypia, mitotic figures, or necrosis are identified. Features are consistent with Angioleiomyoma (Vascular Leiomyoma)."

SECTION 2: DEFINITION AND CLASSIFICATION

SECTION 3: CLINICAL FEATURES

• Age: 40-60 years (middle-aged adults)
• Sex: More common in women (F:M = 2:1)
• Site: Lower extremity > upper extremity > head and neck
  • Lower leg (calf/ankle) and popliteal fossa are the MOST COMMON sites
• Presentation: Slowly growing, painful subcutaneous nodule (pain is characteristic - due to presence of nerve fibers within the tumor reacting to cold/pressure)
• Size: Usually small (1-2 cm), well-demarcated

1. Nerve fibers within the tumor capsule and stroma that are stimulated by pressure or cold
2. Ischemia due to contraction of smooth muscle cells around vessels
3. The venous type (most common) tends to be more painful than the solid or cavernous types

• Female, age 60 - peak age-sex group
• Popliteal fossa (lower extremity) - most common anatomical site
• Subcutaneous location - characteristic
• Likely presented with pain and slowly growing swelling

SECTION 4: HISTOPATHOLOGY (DEEP DIVE)

1. Encapsulation: Well-defined fibrous capsule (partial or complete)
2. Spindle cells: Arranged in interlacing fascicles and whorling bundles
3. Nuclear morphology: Blunt-ended, cigar-shaped, vesicular nuclei with finely granular chromatin - key smooth muscle feature
4. Cytoplasm: Abundant, deeply eosinophilic, fibrillar; perinuclear vacuoles may be seen (especially in uterine type)
5. Vascular component: Numerous thick-walled vessels (arterioles/venules) with smooth muscle walls blending imperceptibly into surrounding tumor cells - this is the DEFINING feature separating it from ordinary leiomyoma
6. Stroma: Collagenous to focally myxoid; scattered lymphocytes and plasma cells
7. NO mitoses, NO atypia, NO necrosis - benign

• Thick-walled muscular vessels with well-developed tunica media
• The smooth muscle of the vessel wall transitions directly into the tumor stroma - there is NO clear boundary between vessel wall and tumor cells
• Lumens may be irregular, slit-like, or round
• Vessels are distributed throughout the entire tumor, not just at the periphery

• Inflammatory Myofibroblastic Tumor (where inflammation is more prominent and ALK+ )
• Inflammatory leiomyosarcoma (where cytological atypia is present)

SECTION 5: IMMUNOHISTOCHEMISTRY

SECTION 6: DIFFERENTIAL DIAGNOSIS

• Has Antoni A (cellular, Verocay bodies) and Antoni B (myxoid, loose) areas
• Nuclei are wavy/buckled, NOT blunt-ended
• S100 strongly positive; SMA negative
• EXCLUDED by nuclear morphology and IHC

• Reactive, NOT neoplastic; not encapsulated
• "Tissue culture" pattern - loosely arranged cells
• Rich myxoid stroma with extravasated red cells ("torn tissue" appearance)
• Usually presents acutely in young adults (<30 years), short history (weeks)
• Self-limiting
• EXCLUDED by encapsulation, age, and smooth muscle morphology

• Infiltrative, NOT encapsulated
• Bland fibroblasts/myofibroblasts in dense collagen
• No significant vascularity
• Nuclear beta-catenin positive
• SMA weakly positive, Desmin negative
• EXCLUDED by encapsulation and SMA/Desmin staining pattern

• Rare in subcutaneous tissue
• CD117+ and DOG-1+
• Associated with KIT/PDGFRA mutations
• EXCLUDED by CD117 and DOG-1 negativity + subcutaneous location

• Marked nuclear atypia (>3-fold variation in nuclear size)
• Mitotic activity >10/10 HPF; atypical mitoses
• Necrosis (coagulative)
• Poor encapsulation, infiltrative borders
• EXCLUDED in this case - no atypia, no mitoses, no necrosis

SECTION 7: SPECIAL STAINS

1. Masson's Trichrome: Smooth muscle stains red/pink; collagen stains blue/green - helps quantify the smooth muscle component
2. PAS (Periodic Acid Schiff): Highlights basement membrane around smooth muscle cells
3. van Gieson's stain: Smooth muscle = yellow; collagen = red

SECTION 8: PATHOGENESIS AND MOLECULAR

• Arises from the smooth muscle cells of the tunica media of small blood vessels (arteries and veins) in subcutaneous tissue
• Not associated with specific genetic mutations (unlike uterine leiomyomas which have MED12 mutations)
• No hormonal dependence demonstrated in soft tissue angioleiomyomas (unlike uterine type)
• The pain may be related to encapsulated nerve fibers within the tumor (demonstrated on S100 and neurofilament staining)

• Uterine leiomyomas: MED12 mutations (70%), HMGA2 rearrangements
• Soft tissue angioleiomyoma: No consistent molecular abnormality identified
• This is a benign, non-aggressive tumor with no malignant potential
• Unlike uterine leiomyomas, estrogen/progesterone receptor expression in soft tissue angioleiomyoma is variable and less consistent

SECTION 9: PROGNOSIS AND TREATMENT

• Treatment: Simple surgical excision with clear margins
• Prognosis: Excellent - benign behavior
• Recurrence: Rare after complete excision (<5%)
• Malignant transformation: Extremely rare (essentially does not occur in subcutaneous angioleiomyoma)
• Post-excision, the patient is cured; no adjuvant therapy required

• In soft tissue: Malignant transformation of a benign leiomyoma/angioleiomyoma to leiomyosarcoma is extremely rare and not well-documented
• In uterus: Leiomyosarcoma arises de novo, NOT from a pre-existing leiomyoma (this is the current consensus)
• The criteria for malignancy in smooth muscle tumors:
  • Mitoses >10/10 HPF (uterus) or >5/10 HPF (soft tissue)
  • Nuclear atypia
  • Coagulative necrosis
  • Infiltrative margins

SECTION 10: COMPARISON TABLE (The Examiner's Favorite)

QUICK MEMORY POINTS FOR TOMORROW

"60F + Popliteal fossa + Painful subcutaneous nodule = Think Angioleiomyoma"

1. Blunt cigar nuclei + eosinophilic fibrillar cytoplasm = SMOOTH MUSCLE
2. Thick-walled vessels throughout = ANGIO- component
3. Encapsulated = BENIGN
4. SMA ++ / S100 -- = NOT a nerve sheath tumor
5. No mitoses, no atypia, no necrosis = BENIGN behavior
6. Simple excision = CURED