Histopathology Slide: Histoid Leprosy (Histoid Hansen's Disease)

Low Power

• Epidermis: Flattened/atrophic, with a clear subepidermal Grenz zone (narrow band of uninvolved papillary dermis separating epidermis from the dermal infiltrate) - this Grenz zone is a lepromatous-spectrum hallmark.
• Dermis: A well-circumscribed, non-encapsulated (occasionally pseudo-encapsulated) nodular cellular lesion filling the dermis and extending into subcutis, giving a "tumor-like" silhouette that can be mistaken at first

Histopathology Slide: Histoid Leprosy (Histoid Hansen's Disease)

Low Power

• Epidermis: Flattened/atrophic, with a clear subepidermal Grenz zone (a narrow band of uninvolved papillary dermis separating the epidermis from the dermal infiltrate) - a hallmark of the lepromatous spectrum.
• Dermis: A well-circumscribed, non-encapsulated (occasionally with a pseudocapsule) cellular nodule filling the dermis and extending into the subcutis - giving a "tumor-like" silhouette that can mimic a fibrohistiocytic tumor (e.g., dermatofibroma) at first glance.

High Power

• Predominant cell type: Sheets of spindle-shaped histiocytes arranged in a storiform (whorled) pattern, closely resembling a benign fibrous histiocytoma. This spindling is the defining feature that gives "histoid" leprosy its name.
• Nuclear features: Nuclear pyknosis within the spindle cells.
• Cytoplasm: Foamy, vacuolated cytoplasm (lepra cells / Virchow cells in spindled form).
• Admixed cells: Scattered polygonal macrophages and a variable, generally sparse, lymphocytic and other inflammatory cell infiltrate.
• Immunophenotype: Spindle cells and macrophages are CD68-positive, confirming histiocytic lineage despite the deceptively fibroblastic/spindled morphology.

Special Stains - Fite-Faraco (modified Ziehl-Neelsen for lepra bacilli)

• Reveals numerous acid-fast bacilli (AFB), characteristically arranged as rafts and globi (dense intracellular clumps), reflecting the very high bacillary index typical of histoid leprosy.
• Bacilli are also found in nerves, Schwann cells, eccrine glands, and vascular endothelium - reflecting the neurotropism and adnexal involvement common to lepromatous-spectrum disease.
• Slit-skin smear correlate: high bacteriologic index, but globi are often absent on smear even though bacilli are abundant histologically in many series.

Key Diagnostic Points / Differentials

One-line Summary for the Slide Label

• Fitzpatrick's Dermatology, 9th ed., p. 2937 (Fig. 159-29, 159-30)
• Andrews' Diseases of the Skin, p. 398
• Harrison's Principles of Internal Medicine, 22nd ed. (Ch. 184)

Histopathology Slide: Histoid Leprosy (Histoid Hansen's Disease)

Low Power

• Epidermis: Flattened/atrophic, with a clear subepidermal Grenz zone (narrow band of uninvolved papillary dermis separating epidermis from the dermal infiltrate) - this Grenz zone is a lepromatous-spectrum hallmark.
• Dermis: A well-circumscribed, non-encapsulated (occasionally pseudo-encapsulated) nodular cellular lesion filling the dermis and extending into subcutis, giving a "tumor-like" silhouette that can be mistaken at first## Histopathology Slide: Histoid Leprosy (Histoid Hansen's Disease)

Low Power

• Epidermis: Flattened/atrophic, with a clear subepidermal Grenz zone (a narrow band of uninvolved papillary dermis separating the epidermis from the dermal infiltrate) - a hallmark of the lepromatous spectrum.
• Dermis: A well-circumscribed, non-encapsulated (occasionally with a pseudocapsule) cellular nodule filling the dermis and extending into the subcutis - giving a "tumor-like" silhouette that can mimic a fibrohistiocytic tumor (e.g., dermatofibroma) at first glance.

High Power

• Predominant cell type: Sheets of spindle-shaped histiocytes arranged in a storiform (whorled) pattern, closely resembling a benign fibrous histiocytoma. This spindling is the defining feature that gives "histoid" leprosy its name.
• Nuclear features: Nuclear pyknosis within the spindle cells.
• Cytoplasm: Foamy, vacuolated cytoplasm (lepra cells / Virchow cells in spindled form).
• Admixed cells: Scattered polygonal macrophages and a variable, generally sparse, lymphocytic and other inflammatory cell infiltrate.
• Immunophenotype: Spindle cells and macrophages are CD68-positive, confirming histiocytic lineage despite the deceptively fibroblastic/spindled morphology.

Special Stains - Fite-Faraco (modified Ziehl-Neelsen for lepra bacilli)

• Reveals numerous acid-fast bacilli (AFB), characteristically arranged as rafts and globi (dense intracellular clumps), reflecting the very high bacillary index typical of histoid leprosy.
• Bacilli are also found in nerves, Schwann cells, eccrine glands, and vascular endothelium - reflecting the neurotropism and adnexal involvement common to lepromatous-spectrum disease.
• Slit-skin smear correlate: high bacteriologic index, but globi are often absent on smear even though bacilli are abundant histologically in many series.

Key Diagnostic Points / Differentials

One-line Summary for the Slide Label

• Fitzpatrick's Dermatology, 9th ed., p. 2937 (Fig. 159-29, 159-30)
• Andrews' Diseases of the Skin, p. 398
• Harrison's Principles of Internal Medicine, 22nd ed. (Ch. 184)

Histopathology Slide: Glioblastoma (IDH-Wildtype, WHO Grade 4)

Gross Appearance

• Poorly demarcated, infiltrating mass, often in the cerebral white matter (frontal/temporal lobes) with extension into gray matter and across the corpus callosum.
• Variegated cut surface: areas of yellow necrosis, hemorrhage, and cystic softening admixed with firmer tumor tissue - historically the basis for the older name "glioblastoma multiforme."

Low Power

• Highly cellular, infiltrative glial tumor with marked nuclear pleomorphism and geographic/serpiginous zones of necrosis.
• Necrotic zones are irregular, serpentine ("serpiginous") pale-pink anucleate areas.
• Tumor hypercellularity is concentrated along the edges of necrosis.

High Power - Key Diagnostic Features

1. Pseudopalisading necrosis: Tumor cell nuclei line up densely around the anucleate necrotic zones, giving a "palisaded" appearance around geographic necrosis - considered a histologic hallmark of glioblastoma.
2. Microvascular proliferation: Glomeruloid tufts of proliferating endothelial cells and pericytes, resembling renal glomeruli, seen at the tumor periphery - reflects the marked angiogenic drive of this tumor (VEGF-mediated).
3. Cellular pleomorphism: Marked variation in cell and nuclear size and shape, with hyperchromatic, often bizarre nuclei; multinucleated tumor giant cells may be seen.
4. Mitotic activity: Brisk, with frequent and sometimes atypical mitoses.
5. Background: Infiltrating astrocytic tumor cells with fibrillary cytoplasmic processes merging into adjacent brain parenchyma (making complete resection essentially impossible).

Diagnostic Criteria (per current WHO classification)

• Microvascular proliferation, or
• Necrosis, or
• One or more of three molecular alterations even in their absence: TERT promoter mutation, EGFR gene amplification, or combined whole chromosome 7 gain / whole chromosome 10 loss (+7/-10)

Immunohistochemistry / Ancillary Studies

• GFAP: Positive, confirming astrocytic/glial lineage (though can be patchy in poorly differentiated areas).
• IDH1 R132H: Negative (by definition of IDH-wildtype glioblastoma; a positive result should prompt reclassification as IDH-mutant astrocytoma).
• Ki-67/MIB-1: High proliferative index, consistent with high-grade malignancy.
• ATRX/p53: Variable; helps distinguish from IDH-mutant astrocytomas which typically show ATRX loss and p53 overexpression.
• MGMT promoter methylation status: Not a diagnostic histologic feature but clinically essential - methylated MGMT predicts better response to temozolomide.

Key Differentials

One-line Summary for the Slide Label

• Robbins & Cotran Pathologic Basis of Disease, 10th ed., p. 830-842 (Fig. 28.48)
• Robbins & Kumar Basic Pathology, p. 2072-2085 (Fig. 21.31)
• Goldman-Cecil Medicine, p. 3899