Case 4 - 180727-4

seven-year-old, male intact English bulldog

The patient was presented for removal of a suspected cutaneous lymphoma overlying the 4th digit of the left pelvic limb. Several months earlier, the patient was presented with a cutaneous mass on a paw pad of the right pelvic limb. That mass was diagnosed as a plasmacytoma on an incisional biopsy, but it was later diagnosed as a pleomorphic, T-cell granular lymphoma on an excisional biopsy

The mass expanded the subcutis and was homogenously firm, smooth and pale pink. The overlying dermis was centrally umbilicated and ulcerated.

Haired Skin: One section of haired skin with a focally-extensive central ulceration is examined. The dermis is expanded by a multinodular, unencapsulated, poorly-demarcated, infiltrative mass composed of sheets of round, pleomorphic cells supported by a dense myxomatous stroma. Cells have distinct cell borders and scant to moderate amounts of pale eosinophilic cytoplasm. Nuclei are pleomorphic and contain finely-stippled chromatin with 1 to 2 distinct nucleoli. Anisocytosis and anisokaryosis are marked with nuclei ranging from 2 to 4 red blood cells in diameter. There are occasional binucleated cells and more rare multinucleated cells. There are 8, frequently bizarre, mitotic figures per ten, 400x fields. Thin streams and small nests of the described cell population frequently infiltrate and dissect adjacent dermal collagen bundles, extending to the cut margins. The mass is multifocally necrotic, characterized by hypereosinophilic, fibrillar material admixed with degenerate neutrophils, pyknotic nuclei and karyorrhectic debris. Large numbers of neutrophils, eosinophils and mast cells percolate throughout the mass. Eosinophilis frequently congregate around dense aggregates of crystalline, brightly eosinophilic material. The ulcerated center is markedly necrotic, hemorrhagic and overlain by dense clouds of bacteria, which frequently tract along numerous draining tracts that extend into the deep dermis and described mass. Remaining adnexal structures at the periphery of the mass are compressed and aprocrine glands are frequently dilated by lakes of pale amphophilic, acellular material.

Immunohistochemistry: An immunohistochemical stain for CD3 was applied to this section. Approximately 10 to 20% of the neoplastic cells exhibit strong cytoplasmic immunoreactivity. The remainder of the neoplastic cell population exhibits faint cytoplasmic immunoreactivity. Approximately 30 to 40% of the neoplastic cells contain strongly-immunoreactive, intracytoplasmic granules when stained with an immunohistochemical assay for granzyme B.

Digital mass: Pleomorphic large granular lymphoma Skin (Digit): Marked acute regionally-extensive necrotizing, ulcerative, and neutrophilic dermatitis with multifocal draining tracts, flame figures and intralesional bacteria

Large granular lymphocytes, both normal and neoplastic, contain intracytoplasmic granules. The number of these granules may increase in lymphoma or leukemia, as well as in a variety of inflammatory and infectious diseases. Large granular lymphomas are believed to be indolent in dogs, however too few cases have been adequately followed to accurately predict their behavior. Large granular lymphomas in cats are aggressive and significantly shorten the cat’s lifespan. Approximately 90% of large granular lymphomas are composed of T-cells, and immunohistochemistry confirmed that the neoplastic cells in this patient were of T-cell origin. Another important feature of this case was the large number of eosinophils scattered among the neoplastic cells. Careful evaluation of the neoplastic cellular morphology is crucial to distinguish T-cell lymphomas from mast cell tumors as both can be characterized by infiltrating eosinophils. Large granular lymphocytes are intermediate to large and have abundant, often clear, cytoplasm with between 3 to 20, variably-sized, perinuclear granules. Granules are easier to see in cytological preparations than histologic preparations and may be more conspicuous with Wright-Giemsa or PTAH stains than H&E or Diff-Quik. Some conference attendants were not certain of the diagnosis of a granular T-cell lymphoma and remain suspicious of a Grade III mast cell tumor. Differentiation between the two could be further investigated through toluidine, blue, methylene blue or giemsa stains. To the contributor’s knowledge, granzyme B does not stain mast cell granules.

1. Donald J. Meuten. Tumors in Domestic Animals. 5th ed. John Wiley & Sons, Inc. 2017.

Case contributor: Dr. Liz Rose, Dr. Natasha Vapniarsky and Dr. Verena Affolter