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Read-Only Case Details Reviewed: Oct 2010



October 2019




Signalment (JPC# 2776270): A dog




HISTOPATHOLOGIC DESCRIPTION: Haired skin: Effacing dermal collagen and adnexa, elevating the epidermis, infiltrating the epidermal and follicular epithelium, and extending into the subcutis and panniculus carnosus is an unencapsulated, infiltrative, poorly demarcated, densely cellular neoplasm composed of round cells arranged in sheets on a preexisting fibrovascular stroma. Neoplastic cells have indistinct cell borders, a moderate amount of eosinophilic cytoplasm, and irregularly round nuclei with finely stippled chromatin and one generally distinct nucleolus. The mitotic rate averages 2 per 40X HPF. Anisocytosis and anisokaryosis are marked. Within the epidermis are clusters of intraepithelial neoplastic lymphocytes surrounded by clear space (Pautrier’s microabscesses). Diffusely within the superficial dermis there is abundant edema, hemorrhage, scant fibrin, and degenerate and non-degenerate neutrophils. The epidermis is focally ulcerated and replaced with a serocellular crust; remaining epidermis is characterized by diffuse parakeratotic hyperkeratosis, multifocal intracorneal pustules, and epidermal hyperplasia (acanthosis).


MORPHOLOGIC DIAGNOSIS: Haired skin: Epitheliotropic lymphoma, breed unspecified, canine.



Signalment (JPC# 4089041): 4-year-old neutered male shepherd mix


HISTORY: 1x1x1cm, cutaneous, superficial, freely moveable mass on digit 4 of the left pelvic limb


HISTOPATHOLOGIC DESCRIPTION: Haired skin: Expanding the dermis, raising the overlying epidermis, infiltrating the epidermal and follicular epithelium, and surrounding and widely separating adnexa is an unencapsulated, poorly demarcated, infiltrative, moderately cellular neoplasm composed of round cells arranged in sheets on a preexisting dense fibrous stroma. Neoplastic cells have variably distinct cell borders, a scant to small amount of eosinophilic cytoplasm, and an irregularly round nucleus with finely stippled chromatin and one distinct nucleolus. Anisocytosis and anisokaryosis is moderate to occasionally marked. There are 8 mitotic figures per 10 40X HPF. Within the epidermis are occasional small clusters of neoplastic lymphocytes surrounded by a clear space (Pautrier’s microabscesses). Within the superficial dermis there are occasional melanomacrophages (pigmentary incontinence). Diffusely within the dermis are low to moderate numbers of neutrophils, plasma cells, and fewer macrophages. The epidermis has diffuse, mild orthokeratotic hyperkeratosis and multifocally there are clear vacuoles within keratinocytes (intracellular edema).



CD3: Haired skin: There is diffuse, strong, membranous immunoreactivity of the neoplastic round cells within epidermal and follicular epithelium and dermis.


MORPHOLOGIC DIAGNOSIS: Haired skin: Epitheliotropic T-cell lymphoma, shepherd mix, canine.


SYNONYMS: Mycosis fungoides, cutaneous epitheliotropic T-cell lymphoma (CTCL)



·      Uncommon (more common in dogs than cats), progressive T-cell lymphoma that affects the skin and mucous membranes

·      Primarily a disease of older animals

·      Poor prognosis due to rapid progression

·      Lesions are usually restricted to the skin, but may be found in multiple tissues

·      Epitheliotropic cutaneous lymphoma encompasses a spectrum of disease:

·      Classic mycosis fungoides (MF)

·      Most common form – strong tropism of neoplastic T cells for epidermis and adnexal structures

·      Sézary syndrome

·      MF with lymphadenopathy and neoplastic cells in the peripheral blood

·      Pagetoid reticulosis (Woringer-Kolopp disease)

·      Localized solitary plaque, neoplastic cells confined to the epidermis/epithelium



·      Pathogenesis unknown

·      In domestic animals:

·      Epitheliotropic lymphomas express T-cell surface antigens (eg. CD3)

·      >80% express CD8 and the γδ T-cell receptor (in contrast to human disease)

·      Humoral hypercalcemia of malignancy

·      Neoplastic T-cells can secrete PTHrP, which is the most consistent factor responsible for hypercalcemia in dogs with lymphoma; neoplastic T-cells also product TNFα and receptor activator of NFκB ligand (RANKL)

·      Increased PTHrP à bind to and activating PTH1 receptors in bone and kidney à hypercalcemia and hypophosphatemia via:

·      Increased osteoclastic bone resorption

·      Increased calcium reabsorption in the renal tubules

·      Decreased phosphorous reabsorption in the renal tubules

·      Activated vitamin D precursors, increasing intestinal absorption of calcium



·      Early lesions can resemble inflammatory skin disease

·      Pruritus is common

·      +/- humoral hypercalcemia of malignancy

·      Gammopathy is rare



·      Pagetoid reticulosis (Woringer-Kolopp disease)

·      Exfoliative erythroderma, scale formation, alopecia, and erosions or ulcerations without the presence of distinct masses

·      Usually solitary, localized lesion

·      Classic MF/Sézary syndrome

·      Patch/plaque progresses to tumor stage

·      Common sites are the head, mouth, feet, and ventral abdomen

·      Metastasis, especially to local lymph nodes, occurs late in the disease



·      The most characteristic lesion, common to all forms of canine epitheliotropic T-cell lymphoma is the tropism of neoplastic cells for epithelium, especially follicular epithelium and apocrine sweat glands

·      Neoplastic T cells are:

·      Intermediate size with a round, hyperchromatic, and convoluted nucleus with occasional sharp, shallow indentations and large nucleoli that are variably distinct

·      Cytoplasm is generally water clear and minimal

·      Mitotic figures are rare

·      Mycosis Fungoides

·      Epidermis: Intraepidermal vesicles contain clusters of pleomorphic lymphoid cells (Pautrier’s microabscesses); or solitary cells surrounded by a clear halo

·      Pleomorphic infiltrate: Composed of histiocytes, plasma cells, eosinophils and non-neoplastic lymphocytes, combined with neoplastic lymphocytes

·      Neoplastic cells have convoluted to cerebriform hyperchromatic nuclei

·      Neoplastic lymphocytes may have a histiocytic appearance

·      Sézary syndrome

·      Sézary cells (cerebriform nuclei) are also present in peripheral blood

·      Pagetoid reticulosis

·      Exhibits almost exclusive invasion of epidermis and adnexa by neoplastic lymphocytes

·      No dermal or subcutaneous involvement

·      Neoplastic cells are either small with hyperchromatic nuclei or may be larger with more cytoplasm



·      Neoplastic cells have a high nuclear to cytoplasmic ratio, deep invaginations of the nuclear membrane (cerebriform pattern), a wide rim of peripheral chromatin, a paucity of organelles, and peripheral cytoplasmic villi or projections



·      Cytology: Sézary cells on blood smear in Sézary syndrome

·      All T-cells are CD3 positive, CD4 negative

·      80% are also CD8 positive

·      Remaining 20% are CD4 negative and CD8 negative

·      Approximately half are γδ-TCR positive and half are αβ-TCR positive

·      Pagetoid reticulosis – all cases are γδ-TCR positive



·      Early nodular disease

·      Inflammatory interface dermatitis: Clinical follow up and subsequent biopsies

·      Nonepitheliotropic cutaneous T-cell lymphoma

·      Hypersensitivity reaction: More severe spongiosis, epidermal hyperplasia, and migration of lymphocytes through the entire epidermis (neoplastic cells usually accumulate in the lower half of the epidermis)

·      Erythema multiforme (I-M29(: Fewer lymphocytes in the epidermis which are usually associated with apoptotic keratinocytes

·      Histiocytic proliferation or neoplasm (I-M10, I-N22, I-N27A): CD3 negative

·      Melanoma (I-N24): CD3 negative

·      Oral lesions:

·      Pemphigus vulgaris (I-M26): Suprabasilar cleft

·      Inflammatory stomatitis: CD3 negative

·      Facial disease (symmetrical with depigmentation)

·      Discoid lupus (I-M28): Lymphoplasmacytic interface dermatitis restricted to face

·      Systemic lupus erythematosus (I-M28): Lymphoplasmacytic interface dermatitis

·      Vogt-Koyanagi-Harada-like syndrome (S-M07): Uveitis, rare basal cell degeneration



·      Cattle: Mycosis fungoides with microscopic features similar to dogs that may progress to systemic disease; usually occurs in 2-year-old bovine leukemia negative cattle

·      Cats: Rare

·      Mycosis fungoides with microscopic lesions similar to dogs

·      Clinical signs: Well-circumscribed exfoliative erythroderma, alopecia, and crusting primarily of head and neck; often misdiagnosed as dermatophytosis or demodicosis

·      Other animals identified with mycosis fungoides: Rat, hamster, horse (thoroughbreds have increased frequency), rabbit, alpaca, opossum



1.     Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: John Wiley & Sons, Inc.; 2016:170, 205.

2.     Bienzle D. Hematopoietic Neoplasia. In: Latimer KS, ed. Duncan & Prasse’s Veterinary Laboratory Medicine Clinical Pathology. 5th ed. 2001: John Wiley & Sons, Inc.; 2011:89.

3.     Brachelente C, Affolter VK, et al. CD3 and CD20 coexpression in a case of canine cutaneous epitheliotropic T-cell lymphoma (mycosis fungoides). Vet Pathol. 2016;53(3):563-566.

4.     Gross TL, Ihrke PJ, Walder EJ, et. Lymphocytic tumors. In: Gross TL, Ihrke PJ, Walder EJ, et al., Skin Diseases of the Dog and Cat. 2nd ed. Ames, IA: Blackwell Science Ltd; 2005:876-882.

5.     Hasbach AE, Stern, AW. Pagetoid reticulosis (epitheliotropic cutaneous T-cell lymphoma) in an adult alpaca (Vicugna pacos). J Vet Diagn Invest. 2016;28(4):469-472.

6.     Higbie CT, Carpenter JW, et al. Cutaneous epitheliotropic T-cell lymphoma with metastases in a Virginia opossum (Didelphis virginiana). J Zoo Wildl Med. 2015;46(2):409-413.

7.     Mauldin EA, Peters-Kennedy J. Integumentary system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016:733-735.

8.     Miller CA, Durham AC, et al. Classification and clinical features in 88 cases of equine cutaneous lymphoma. J Vet Diagn Invest. 2015;27(1):86-91.

9.     Mineshige T, Kawarai S, et al. Cutaneous epitheliotropic T-cell lymphoma with systemic dissemination in a dog. J Vet Diagn Invest. 2016;28(3):327-331.

10.  Raskin, RE. Skin and Subcutaneous Tissues. In: Raskin RE, Meyer DJ, eds. Canine and Feline Cytology: A Color Atlas and Interpretation Guide. 3rd ed. St. Louis, MO: Elsevier; 2016:82-84.

11.  Rosol TJ, Gröne A. Endocrine Glands. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. St. Louis, MO: Elsevier; 2016:306,309.

12.  Valli VEO, Kuipel M, Bienzle D. Hematopoietic System. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. St. Louis, MO: Elsevier; 2016:232-4.

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