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Cutaneous T-cell lymphoma, NK-cell lymphoma, and myeloid leukemia


Cutaneous T-cell lymphoma and NK-cell lymphoma

Mycosis fungoides

Patch stage

Key Features

  • Lymphocytes “line up” along the dermal–epidermal junction (simulates vacuolar interface dermatitis, with a “lymphocyte in every hole”)

  • Large dark lymphocytes with irregular nuclear contours and perinuclear haloes (“lump of coal on a pillow”)

  • Pautrier microabscesses (intraepidermal clusters of atypical lymphocytes, larger than the benign recruited dermal lymphocytes)

  • Mild bandlike infiltrate in superficial dermis

  • Sclerosis of the papillary dermis

  • Eosinophils and necrotic keratinocytes are rarely present

Mycosis fungoides (MF) is the most common type of cutaneous lymphoma. In most cases, the disease is indolent and slowly progressive over a period of years or decades. Three main stages of the lymphoma are recognized: patch, plaque, and tumor. In the patch stage of MF, patients typically present with broad pink or tan, oval-shaped patches with a predilection for the bathing trunk area. The patches may be asymptomatic or pruritic. Both clinically and histopathologically, distinction from eczematous dermatitis is sometimes difficult in the earliest stages of the lymphoma. In the evaluation of patch-stage MF, multiple shave biopsies are often helpful, because the shave technique provides a broad area of epidermis for examination. The typical immunophenotype is CD3+, CD4+, CD8−, CD30−. Aberrant immunophenotypes (with loss of normal T-cell markers, such as CD7) can frequently be demonstrated. Clonal rearrangement of the T-cell receptor gene is helpful in supporting the diagnosis, although the earliest cases may sometimes not have a detectable clone.

Differential Diagnosis

  • Dermatitis generally has more spongiosis and fewer intraepidermal lymphocytes.

  • Lichenoid drug eruption typically has more apoptotic keratinocytes and eosinophils.

  • Lymphomatoid drug eruption may look nearly identical. Pautrier microabscesses favor MF.

Fig. 24.1, Patch-stage mycosis fungoides

Table 24.1
Mature T and NK neoplasms characteristically involving the skin in the 2016 revision of the WHO classification of lymphoid neoplasms.
Data from Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood . 2016;127(20):2375–2390.

  • Mycosis fungoides

  • Sézary syndrome

  • Adult T-cell leukemia/lymphoma

  • Primary cutaneous CD30+ T-cell lymphoproliferative disorders

    • Lymphomatoid papulosis

    • Primary cutaneous anaplastic large cell lymphoma

  • Subcutaneous panniculitis-like T-cell lymphoma

  • Extranodal NK/T-cell lymphoma, nasal type

  • Peripheral T-cell lymphoma, NOS

  • Primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma *

  • Primary cutaneous gamma–delta T-cell lymphoma

  • Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder *

  • Follicular T-cell lymphoma *

  • Angioimmunoblastic T-cell lymphoma

  • Primary cutaneous acral CD8+ T-cell lymphoma *

  • Hydroa vacciniforme-like lymphoproliferative disorder

* Asterisk indicates provisional entities.

Fig. 24.2, Patch-stage mycosis fungoides

Plaque stage

Key Features

  • Like patch stage, but with a denser, bandlike infiltrate in the upper dermis

  • Atypical lymphocytes present in the dermal band

Fig. 24.3, Plaque-stage mycosis fungoides

Tumor stage

Key Features

  • Dense, nodular lymphocytic infiltrate in the superficial and deep dermis

  • Many atypical lymphocytes present in the dermal infiltrate

  • Transformation to large-sized lymphocytes in some cases

  • Acquisition of CD30 expression in some cases

  • Loss of epidermotropism with progression

Over time, patients with MF may progress to develop thicker plaques and tumors. Whereas patch-stage MF is usually associated with long survival, the prognosis is poorer for those patients who progress to the tumor stage.

Fig. 24.4, Tumor-stage mycosis fungoides

Fig. 24.5, Tumor-stage mycosis fungoides

Fig. 24.6, Tumor-stage mycosis fungoides

Pagetoid reticulosis variant

Key Features

  • Solitary or multiple patches or plaques on distal extremities

  • Atypical large lymphocytes extensively infiltrating the epidermis

  • CD3+

  • CD4+ CD8− or CD4− CD8+

  • Small reactive lymphocytes in papillary dermis

The term pagetoid reticulosis is now limited to the Woringer–Kolopp type, which presents as one or several patches or plaques on the distal extremities. This type of lymphoma is associated with an excellent prognosis. The disseminated Ketron–Goodman type of pagetoid reticulosis has been reclassified into several other types of cutaneous T-cell lymphoma.

Fig. 24.7, Pagetoid reticulosis variant of mycosis fungoides

Folliculotropic variant

Key Features

  • Atypical lymphocytes infiltrate the follicular epithelium

  • Basaloid induction and hyperplasia of follicular epithelium

  • Eosinophils common

  • Follicular mucinosis (pools of mucin in the follicular epithelium)

  • Epidermis usually spared

  • CD3+, CD4+, and CD8− in most cases

The folliculotropic variant of MF presents with follicular papules and boggy plaques, most frequently involving the head and neck. Follicular mucinosis is often present. Folliculotropic MF is generally associated with earlier progression than conventional MF.

Fig. 24.8, Folliculotropic variant of mycosis fungoides

Granulomatous slack skin

Key Features

  • Pendulous folds in intertriginous regions

  • Preceded by insidious onset of patches, papules, and plaques

  • Massive dermal and subcutaneous infiltrate ± epidermal involvement

  • Small T lymphocytes with epidermotropism and mild cytologic atypia

  • Huge multinucleate giant cells with numerous nuclei, often in wreathlike arrangement

  • Phagocytosis of lymphocytes by multinucleate cells

  • Dermal edema or fibrosis

  • Loss of dermal elastic tissue fibers

  • CD3+, CD4+, and CD8− immunophenotype

Granulomatous slack skin syndrome is an extremely rare variant of MF with a slowly progressive clinical course. The clinical presentation is striking. In fully developed cases, massive folds of skin extend from flexural areas, such as the axillae or groin. An association with nodal Hodgkin lymphoma has been documented in multiple cases.

Fig. 24.9, Granulomatous slack skin variant of mycosis fungoides

Fig. 24.10, Granulomatous slack skin variant of mycosis fungoides

Sézary syndrome

Key Features

  • Erythroderma with generalized pruritus

  • Palmoplantar keratoderma

  • Generalized lymphadenopathy

  • Peripheral blood Sézary cell count of ≥1000 cells/microliter

  • Peripheral blood lymphocytes with aberrant phenotype or CD4/CD8 ratio >10

  • Clonal rearrangement of T-cell receptor genes in blood and/or skin

  • Histopathology like MF, or may show only nonspecific dermatitis

Although previously believed to be a leukemic variant of MF, Sézary syndrome is now considered to originate from a different subset of T cells (central memory T cell in Sézary syndrome versus skin resident memory T cell in MF). In contrast to MF, Sézary syndrome has a rapidly progressive clinical course and a poor prognosis. The diagnosis is confirmed by evaluation of the peripheral blood. Skin biopsy is sometimes useful in demonstrating a histopathologic pattern similar to MF. It should be recognized, however, that skin biopsy findings may be nondiagnostic in some cases of Sézary syndrome. In an erythrodermic patient, nonspecific biopsy findings (such as spongiotic dermatitis) do not exclude the diagnosis. It is important to evaluate the peripheral blood if there is clinical suspicion for Sézary syndrome.

Fig. 24.11, Sézary syndrome

Adult T-cell leukemia/lymphoma (ATCLL)

Key Features

  • Endemic in Japan, Caribbean, southeastern United States, and central Africa

  • Hypercalcemia

  • Osteolytic bone lesions

  • Organomegaly

  • Lymphadenopathy

  • Dermal and/or subcutaneous lymphoid infiltrates

  • T cells with multilobed nuclei

  • Epidermotropism in some cases

  • CD3+, CD4+, CD8−, and CD25+ neoplastic cell population in blood, nodes, and skin

  • Peripheral blood flower cells with multilobed nuclei

  • Clonal integration of the HTLV-1 genome within neoplastic cells

  • Clonal rearrangement of T-cell receptor genes

Adult T-cell leukemia/lymphoma is remarkable for its well-established viral etiology, that is, human T-cell leukemia virus type 1 (HTLV-1). HTLV-1 infection is transmitted by sexual contact, blood transfusion, and mother-to-child vertical transmission. In areas with the highest rates of HTLV-1 infection, such as southwestern Japan, only a relatively small percentage of infected individuals eventually develop the lymphoma or leukemia. ATCLL may occur as an acute or smoldering disease. The skin is involved in up to 50% of patients. Nodules, papules, and plaques may occur. The most specific diagnostic finding is the clonal integration of the HTLV-1 genome within lymphoma cells. This feature is helpful in distinguishing the smoldering variant of ATCLL from MF.

Fig. 24.12, Adult T-cell leukemia/lymphoma

Fig. 24.13, Adult T-cell leukemia/lymphoma

Fig. 24.14, Adult T-cell leukemia/lymphoma

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