Patch and Plaque Stage Mycosis Fungoides

Dear Editor,

Mycosis fungoides (MF), a disease of middle-aged and older individuals, accounts for approximately 50% of diagnosed primary cutaneous T-cell lymphoma cases.^[1] It is clinically suspected in patients with ≥1 longstanding, progressive patches or plaques, of variable size and shape, preferentially involving the sun-protected sites [Figure 1].^[2] Epidermotropism, atypical lymphocytes, epidermal lymphocytes appearing larger than dermal lymphocytes, lymphocytes in a linear distribution along the basal layer and/or in small clusters within the epidermis, pericellular halo around epidermal lymphocytes, vacuolar interface dermatitis, band-like lymphocytic infiltration in superficial dermis and wiry papillary dermal fibrosis are the histopathological attributes of MF.^[2,3] MF is considered ‘the great imitator’ of modern dermatopathology.^[1] This is particularly true for early MF which may exhibit non-specific clinical or inconclusive histopathologic features and mimic many inflammatory dermatoses.^[4] This paper describes the histopathologic pattern seen in recently diagnosed cases of patch and plaque-stage MF at our centre.

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Figure 1:

Dull erythematous, thin plaque with fine scaling over the (a) waist and (b) thigh of a patient diagnosed with mycosis fungoides. (c) Erythematous plaques with minimal scaling over the back of a patient, confirmed histopathologically as mycosis fungoides.

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There were four male and four female patients, and their ages ranged from 47 to 73 years. Five patients were diagnosed with the patch stage of MF, two with plaque MF and one case revealed features of plaque MF progressing to the tumour stage. The frequency of different histopathological attributes in these cases is presented in Table 1.

Epidermotropism or the epidermal infiltration of mononuclear cells in the absence of spongiotic microvesiculation, considered a critical feature of early MF, was noted in all our cases [Figure 2 a-e].^[3] However, a more appropriate description that can help distinguish MF, from eczema is ‘disproportionate epidermotropism’, that is epidermal lymphocytic infiltration disproportionately high relative to the degree of spongiosis. In all our cases, the epidermal lymphocytes appeared larger than their dermal counterparts. The epidermal lymphocytes may be found singly or in pagetoid spread, usually in a linear arrangement along the basal layer (basilar epidermotropism) [Figure 2b,c], and rarely in clusters. Besides MF, epidermotropism has also been described in other subtypes of cutaneous T-cell lymphoma (CTCL) and lymphomatoid papulosis.

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Figure 2:

(a) Multiple lymphocytes, some atypical (red arrows), in a linear arrangement along the basal layer and forming clusters in the upper dermis. Pericellular halo seen around epidermal lymphocytes (H&E ×40). (b and c) Epidermal hypoplasia with multiple lymphocytes (blue arrow) in a linear distribution along the basal layer that appear larger than the dermal lymphocytes. The dermis shows dense lymphocytic infiltration, colloid bodies and pigment incontinence (H&E ×40). (d and e) Prominent basilar epidermotropism, a focus of Pautrier’s microabscess (yellow arrow), and basal cell vacuolation seen in epidermis. Atypical lymphocytes seen in epidermis and dermis (yellow asterisk) and condensed collagen seen in the papillary dermis (H&E ×40). H&E: Haematoxylin and Eosin.

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Another distinctive feature of MF is the presence of lymphocytes surrounded by a clear space due to contracted cytoplasm, appearing as ‘haloed cells’.^[2,3] It was identified as the sole distinguishing feature between MF and its inflammatory mimickers; however, we observed it in only one case of patch-stage MF [Figure 2a].^[4] The atypical lymphocytes, also termed ‘Sezary cells’ or ‘mycosis cells’, were observed in 62.5% of our cases [Figure 2a,d,e]. They are slightly larger in size and are identified by their hyperchromatic, pleomorphic nucleus with convoluted or cerebriform appearance.^[2] Atypical lymphocytes may not always be seen in the epidermal or dermal infiltrate of early MF and hence are not mandatory for the diagnosis.^[5] Small epidermal collections of atypical lymphocytes forming Pautrier’s microabscesses, though a highly specific finding, are rare in early MF and were detected in only two cases of plaque MF [Figure 2d].

Epidermal changes, such as epidermal hypoplasia, spongiosis and basal cell vacoulation, show variable association with MF, as seen in our cases. The dermal lymphocytes, irrespective of their morphology, are arranged either in a band-like pattern along the dermo-epidermal junction or exhibit perivascular arrangement, with the former pattern seen in 50% of all our cases, particularly plaque MF cases. Thickening of collagen in papillary dermis, usually seen in late patch and plaque MF, was detected in just over one-third of the cases.

The International Society for Cutaneous Lymphoma has proposed a diagnostic algorithm for classic early MF that incorporates clinical, histopathologic, molecular and immunopathologic criteria.^[2] Immunohistochemistry may demonstrate a loss of one or more of the pan-T-cell markers, CD 2, 3, 5 and 7, either limited to the epidermis (epidermal/dermal discordance) or seen throughout the skin infiltrate and an increase in CD4:CD8 ratio.^[1] Diagnosis of MF through detection of clonal T-cell receptor gene rearrangement by polymerase chain reaction has a sensitivity ranging from 50% to >70%, depending on the methodology, tissue processing and stage of lesions, with a specificity of 86%.^[1] However, the sensitivity of both tests in diagnosing early MF is low and may rarely also be positive in some inflammatory conditions.^[1,2] Hence, the diagnosis of early MF primarily relies on light microscopy.^[4]

In conclusion, histology interpretation is often subjective, leading to interindividual variability in diagnosing MF and distinguishing it from benign inflammatory mimickers. A combination of cardinal features such as medium-large, monomorphic lymphoid cells with cerebriform nucleus in epidermis or forming clusters in dermis, disproportionate band-like epidermotropism, Pautrier’s microabscesses, haloed lymphoid cells, and absence of microvesiculation are strongly suggestive of a diagnosis of early MF on histology. Epidermotropism and epidermal lymphocytes appearing larger than dermal lymphocytes were the only features observed in all our cases, while other histopathologic findings were variably present.