Table of Content

Current Issue

Autumn 2020, Vol. 28 No. 3

Hong Kong J. Dermatol. Venereol. (2020) 28, 115-120


Case Report

A case of primary cutaneous CD30 positive anaplastic large cell lymphoma in a patient with granulomatous mycosis fungoides

一例肉芽腫性蕈狀肉芽腫患者的原發性皮膚CD30陽性間變性大細胞淋巴瘤

JE Seol, GJ Cho, JU Kim, SH Park, WJ Jin, H Kim

Abstract

Granulomatous mycosis fungoides (MF) is an unusual type of MF, characterised by granulomatous infiltration. Since both primary cutaneous anaplastic large cell lymphoma and large cell transformation of MF may involve CD30+ lymphocytes, it is hard to differentiate between them. However, it is important to make a definitive diagnosis due to the different prognoses. Herein, we present a rare type of MF that was initially misdiagnosed, and was coexistent with primary cutaneous anaplastic large cell lymphoma.

肉芽腫性蕈狀肉芽腫是不常見的蕈狀肉芽腫類型,其特徵是肉芽腫浸潤。由於原發性皮膚間變性大細胞淋巴瘤和蕈狀肉芽腫的大細胞轉化皆可能涉及CD30陽性淋巴細胞,區分有一定難度。但由於各自預後不同,明確的診斷不容易視。在這裡,我們介紹了一種罕見的蕈狀肉芽腫,它最初曾被誤診,並且與原發性皮膚間變性大細胞淋巴瘤並存。

Keywords: Granulomatous mycosis fungoides, large cell transformation, mycosis fungoides, primary cutaneous anaplastic large cell lymphoma

關鍵詞: 肉芽腫性蕈狀肉芽腫、大細胞轉化、蕈狀肉芽腫、原發性皮膚間變性大細胞淋巴瘤

Case report

A 56-year-old male patient presented with a 2-month history of a painful erythematous ulcerative plaque on his left wrist (Figures 1a, 1b). He had first visited our clinic two years previously with an asymptomatic erythematous/hyperpigmented scaly patch, plaque on his left buttock and right thigh (Figures 1c, 1d), that had been present for several years. The patient denied symptoms of weight loss, fever, or night sweats. Histopathological findings from the left buttock biopsy showed a band-like infiltration along the dermo-epidermal junction and perivascular inflammatory cell infiltration in the dermis (Figure 2a). Using a high-powered view, lymphocytic exocytosis with sparse spongiosis in the epidermis was observed (Figure 2b), and the infiltration consisted of small-sized lymphocytes in the dermis (Figure 2c). Given the uncertain diagnosis of interstitial granuloma annulare, four sessions of intralesional triamcinolone injections were administered to the lesions, which showed mild improvement. However, the patient did not followed-up on a regular basis.

Figure 1 (a), (b) The patient had a painful erythematous ulcerative plaque on his left wrist. The patient first visited our clinic two years earlier with (c) an asymptomatic brownish scaly patch on the left buttock and (d) right thigh that had been present for several years. The patient re-visited our clinic and showed mild improvement, but with (e) new surface nodules on the left wrist and (f) enlargement of the left buttock lesions and (g) right thigh lesions.

At the most recent presentation, there was a left wrist lesion from which an incisional biopsy was performed. The biopsy specimen revealed dense interstitial and perivascular infiltration (Figure 2d), composed of small-sized atypical lymphocytes with hyperchromatic nuclei and large, pleomorphic lymphocytes with a few scattered eosinophils and plasma cells (Figure 2e). The majority of the large lymphocytes showed positivity for CD3, CD4, CD8, CD30, and TIA-1, but negativity for CD20 and anaplastic lymphoma kinase (ALK) (Figures 2f-k). In situ hybridisation test for Epstein-Barr virus was negative. T-cell receptor (TCR) gene rearrangement showed monoclonality. Therefore, a diagnosis of primary cutaneous anaplastic large cell lymphoma (pcALCL) was made.

Figure 2 (a) Histopathological examination of the left buttock two years earlier showed band-like infiltration into the dermo-epidermal junction and perivascular inflammation in the upper dermis (H&E, x40). (b) High power view. Lymphocytic exocytosis with patchy spongiosis at the epidermis level (H&E, x400). (c) Perivascular infiltration with small-sized lymphocytes at the dermis level were found (H&E, x400). (d) Histopathological examination of the left wrist lesion showed dense interstitial and perivascular infiltration (H&E, x40). (e) High power view. Infiltration of atypical lymphocytes with hyperchromatic nuclei and large, pleomorphic lymphocytes with abundant cytoplasm and a few eosinophils and plasma cells were observed (H&E, x400). Immunohistochemistry showed (f) CD3 positivity, (g) focal positivity for CD4, (h) focal positivity for CD8, (i) strong positivity for CD30, (j) negativity for CD20, (k) anaplastic lymphoma kinase (ALK) negative.

After two months, the skin lesion on the left wrist showed mild improvement, with no new erythematous nodules (Figure 1e). However, the left buttock and right thigh lesions had deteriorated, with surface nodules on mildly enlarged and slaking skin (Figures 1f, 1g). Further biopsies of the lesions on the left wrist and right thigh were taken. The specimen at the wrist lesion showed dense infiltration through the entire dermis without folliculotropism (Figure 3a). The infiltration was composed of atypical small and large lymphocytes with eosinophils (Figure 3b), which was compatible with diagnosis of pcALCL.

Meanwhile, histopathological findings from the right thigh lesion showed a band-like infiltration in the upper dermis with perivascular granulomatous infiltration in the middle and lower dermis (Figure 3c). In the high-powered view, epidermotropism along the epidermis was observed (Figure 3d), along with infiltration of numerous multinucleated giant cells, small lymphocytes and histiocytes (Figure 3e). There was positivity for CD3 and negative for CD30, resulting in a diagnosis of granulomatous mycosis fungoides (MF) (Figures 3f, 3g). T cell receptor gene rearrangement test showed monoclonality. Since a similar pattern of epidermotropism and atypical lymphocytic infiltration with monoclonality at TCR gene rearrange test was observed in the left buttock lesion, the original diagnosis was revised to granulomatous MF.

Figure 3 (a) The re-biopsied specimen taken from the left wrist lesion showed dense infiltration along the entire dermis (H&E x40). (b) High power view: atypical small and large lymphocytes and several eosinophils were observed (H&E x400). (c) The re-biopsied right thigh lesion showed band-like infiltration into the upper dermis and perivascular infiltration into the middle and lower dermis (H&E x40). (d) There was epidermotropism in the epidermis (H&E x200). (e) Multinucleated giant cells with small lymphocytes and histiocytes infiltration were observed in the dermis (H&E x400) (red arrows: multinucleated giant cells). (f) Immunohistochemistry revealed CD3 positivity. (g) CD30 negativity.

The results of routine laboratory studies were within the normal range, and bone marrow biopsy presented no abnormal findings. On positron emission tomography (PET) revealed hypermetabolic lesions in the left forearm, left wrist, and right thigh, with invasion of both axillary and inguinal lymph nodes. According to the Ann-Arbor staging system for lymphoma, a diagnosis of stage IV was made. After six cycles of chemotherapy with CHOP regimen (cyclophosphamide, hydroxyl-doxorubicin, vincristine and prednisone) for four months, the skin lesions were reduced and follow-up PET showed markedly decreased glucose uptake in all of the pcALCL and MF lesions, thus achieving complete remission. There has been no recurrence during two years of regular follow-up.

Discussion

Primary cutaneous T-cell lymphomas include MF, Sezary syndrome, CD30+ T-cell lymphoproliferative disorders, and primary cutaneous peripheral T-cell lymphoma.1,2 The clinicopathological similarities of the primary cutaneous T-cell lymphomas including MF and pcALCL make it difficult to distinguish between the two conditions.

Mycosis fungoides, defined as proliferation of atypical epidermotropic T-helper lymphocytes exhibiting a CD3+ CD4+ CD45RO+, has an indolent clinical course at the patch/plaque stages.3 Among several subtypes, granulomatous MF is a rare variant that resemble granulomatous disorders.2 Histologically, lichenoid infiltrate of CD4+, CD8- lymphocytes with interstitial histiocytes and/or perivascular granulomas with giant cells are observed.3 Prognosis is more aggressive than classic MF.3 Some MF lesions (8-55%) undergo large cell transformation (LCT-MF), thereby acquiring CD30 positivity.4 The transformation can be histologically defined as more than 25% of large atypical lymphocytes (size of four times larger than a small, mature lymphocyte) showing either CD30+ or CD30-.5 LCT-MF may occur as a solitary nodule within preexisting MF and occurs de novo by metastatic spread of a malignant T-cell clone.5,6 In many of these cases, differentiation is supported clinically based on a history of pre-existing MF.

pcALCL is a cutaneous tumour of large cells with an anaplastic, pleomorphic, or immunoblastic cytomorphology. Over 75% of the tumour cells express CD30 antigen.1,2 Most patients complain with solitary nodules or tumours, and they often ulcerate.6 Multifocal lesions are observed in 20% of patients, and extracutaneous dissemination occurs in approximately 10%.2,6

Since both LCT-MF and pcALCL may express CD30 antigen and show localised lesions, the differential diagnosis between LCT-MF and pcALCL is challenging. However, the distinction is crucial, because of different prognosis of LCT-MF and pcALCL. The overall survival rate at 5 years was 11-32% for LCT-MF and 95% for pcALCL.7

Fauconneau et al. compared the clinical, pathological, and prognostic features of LCT-MF and pcALCL. Age under 60, a small number with localised lesions, less truncal involvement, and spontaneous regression were more often related to a diagnosis of pcALCL than LCT-MF.3,8

Histopathologically, lesions comprising 25-75% of large anaplastic CD30+ cells are more compatible with LCT-MF.5 However, when CD30+ cells constitute more than 75% of a lesion, other features are helpful for differential diagnosis. While one-third of LCT-MF present with folliculotropism of small cerebriform cells, pcALCL does not.5 ALK may be expressed in pcALCL, but is not expressed in LCT-MF. Some ALCL specimens are also known to express TIA-1 and perforin more frequently than LCT-MF.3,8

Our patient's buttock and thigh lesions had been regarded as granulomatous dermatitis. However, resistance to treatment, slack skin appearance, and monoclonality of TCR gene rearrangement suggested granulomatous MF.

Almost all of the large cells in the patient's left wrist lesion showed strong positivity for CD30+; the lesion also showed focal positivity for TIA-1 at initial biopsy. The patient was younger than 60 years old and had a small number of localised lesions. Retrospectively, in contrast to the aggressive clinical course of LCT-MF, the lesion remained indolent for four months before chemotherapy, and complete remission was achieved by chemotherapy with CHOP regimen. Thus, by integrating his clinical, histological characteristics and clinical course, his left wrist lesion was more compatible with pcALCL rather than LCT-MF.

According to the World Health Hematopoietic and Lymphoid Tissues, patients with pcALCL should show no evidence of LyP, MF, or any another type of cutaneous T-cell lymphoma (CTCL); however, in reality, pcALCL can develop secondary to MF.1,9,10 Moreover, MF and another CD30+ lymphoproliferative disorder, LyP, can coexist, in that LyP and pcALCL represent each end of a clinicopathological spectrum of CD30+ lymphoproliferative disorders, and patients with MF patches may also develop tumours that present as pcALCL.10 Hallermann et al stated there is an underestimation of a secondary lymphoid neoplasms in patients with cutaneous lymphoma.11

In our patient, a solitary ulcerative tumour lesion on the wrist emerged subsequent to granulomatous MF that had already been present for several years. The patient was diagnosed with pcALCL coexistent with granulomatous MF. This case shows a rare case of granulomatous MF, presents a process of differentiating pcALCL from LCT-MF, and implies the increased possibility of concurrence of lymphoid neoplasms.

References

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