Cutaneous Lymphomas and Histiocytoses

Mycosis Fungoides/Sezary Syndrome (MF/SS) – most common cutaneous lymphoma

monoclonal CD4⁺ (rarely CD8⁺) T-cell lymphoma
cells express CD2, CD3, and CD5, but usually do not express CD7

Presentation – begins as patches or plaques, progresses to skin tumors, lymph nodes, blood, viscera, sepsis

can translocate throughout SALT (skin associated lymphoid tissue) to lymphatics and bloodstream

subclone tumors can therefore appear throughout the body

Sezary Syndrome variant often includes leukemia, erythroderma, lymphadenopathy

second hit transformation to large cell lymphoma occurs in a small minority of patients – poor prognosis

Histopathology – microabcesses consisting of epidermotropic band-like infiltrate of lymphoid cells with hyperchromatic nuclei

Diagnosis – molecular biology (Southern blot or PCR) to confirm

Treatment – topical nitrogen mustard, PUVA (psoralin and UVA), total skin electron beam radiation, systemic chemotherapy

Other Cutaneous Lymphomas

appear as cutaneous tumor nodules

can present with primary, concurrent, or secondary skin involvement

monoclonal, can be B-cell or T-cell – most T-cell are CD4⁺

Presentation – generally appear as cutaneous tumor nodules from the beginning, rather than patches or plaques

unlike mycosis fungoides, most cutaneous lymphomas do not home to the epidermis

follicular lymphomas – from B-cell follicles

Cutaneous Lymphoid Hyperplasia (CLH)

reactive rather than malignant growth

usually idiopathic; sometimes a foreign antigen is identified (spirochetes, arthropod, vaccination, drugs, trauma)

polyclonal normal B-cells and T-cells (either may predominate) – occasionally, occult monoclonal growth is detectable

Presentation – presents as localized nodules or plaques, usually on head or neck; often chronic

Histopathology – lymphoid infiltrate throughout dermis – may be nodular or diffuse

epidermis is uninvolved, separated from the infiltrate by a Grenz zone of normal papillary dermis
secondary lymphoid follicles with B-cell germinal centers may be present, even when infiltrate appears totally diffuse

Treatment – excision, intralesional corticosteroids, cryotherapy, local radiation therapy – sometimes relapse occurs

occult monoclonal T-cells or B-cells can progress to overt lymphoma

Leukemia Cutis

usually secondary to bone marrow/blood leukemia; most often chronic lymphocytic leukemia

Presentation – macules, papules, plaques, nodules, ecchymoses, palpable purpura, ulcers, hemorrhagic complications

acute monocytic (AMoL) and acute myelomonocytic leukemia (AMML) also exhibits gingival hypertrophy

chronic leukemia (CLL) also exhibits erythroderma and bullae

chronic myelogenous leukemia exhibits granulocytic sarcomas (chloromas) – nodules with myeloperoxidase (green)

can indicate development of blast crisis

Histopathology – varies depending upon type of leukemia – all have large cells with rounded nuclei

AMoL and AMML exhibit perivascular diffuse cellular infiltrate into dermis and subcutis

Histiocytoses

primary proliferative disorders of histiocytes – all are rare, most are benign

distinct from lipidosis (hereditary disorder of lipid metabolism) in which lipid-laden macrophages accumulate in tissues

histiocytes divided into disorders of histiocytic dendritic cells (Langerhans) and macrophages; both derived from bone marrow

Histiocytosis X – diseases of antigen presenting cells (dendritic cells – Langerhans’ cells, interdigitating cells)

variably dense dermal/epidermal infiltration of histiocytes with kidney-shaped nucleus, S100, CD1a⁺ (like Langerhans’)

(1) Eosinophilic Granuloma – discrete nodules involving bone, lung, skin or other tissues

mild, most common in older children and adults, requires no treatment

(2) Hand-Shuller-Christian Disease – diabetes insipidus, exophthalmos, bone defects, papules, plaques

intermediate, most common in children, requires chemotherapy

(3) Letterer-Siwe Disease – fever, cytopenias, hepatosplenomegaly, lymphadenopathy, diffuse pulmonary infiltration, scaly papules

severe, most common in infants, often fatal regardless of treatment

Malignant Histiocytosis/True Histiocytic Lymphoma – deadly malignancies of macrophages; very rare

dermal infiltrate of macrophages (no S100 or CD1a), often with phagocytized RBC’s and WBC’s
lymphoreticular pattern can be parenchymal (true histiocyctic lymphoma) or sinusoidal (malignant histiocytosis)
exhibits papules, plaques, nodules, also lymphadenopathy and splenomegaly

Cutaneous Metastases – 3% of internal tumors metastasize to the skin; very bad sign (survival = few months)

incidence parallels incidence of primary neoplasm

men: lung, colon, melanoma, kidney, stomach

women: breast, lung, colon, ovary, melanoma

can localize anywhere on skin via blood – breast and oral cavity can also metastasize to overlying skin via lymphatics
appear as dermal or subcutaneous nodules, histopathologically like primary tumor

breast cancer skin metastases appears inflammatory, telangiectatic, diffusely indurated (carcinoma en cuirasse)

sometimes skin metastasis is presenting sign of disease (esp. lung or kidney tumors)

e.g., "Sister Mary Joseph’s nodule" -umbilical skin metastasis that is the first sign of abdominal adenocarcinoma