Cutaneous composite lymphoma of mycosis fungoides and Hodgkin lymphoma: Response to sequential therapy

Composite lymphoma is defined as two or more morphologically and immunophenotypically distinct lymphoma clones that occur in the same tissue site. The occurrence of cutaneous composite lymphoma (CCL) is extremely rare. Here we report a unique case of CCL consisting of Hodgkin lymphoma (HL) and mycosis fungoides (MF). Our patient presented with longstanding erythematous plaques on the skin and later developed axillary lymph node enlargement. Histopathologically, the skin lesions were characterized by a dense dermal lymphocytic infiltrate with prominent epidermotropism of pleomorphic T-cells, consistent with typical MF. Nonetheless, scattered large atypical cells resembling Reed-Sternberg (R-S) cells were interspersed among these atypical T-cells in the deep dermis. Immunophenotyping suggested a HL origin of these R-S cells. Monoclonality of T-cell receptor beta gene was detected in the skin, monoclonal immunoglobulin heavy chain gene rearrangement was identified in these R-S cells microdissected from the deep dermis, confirming the origin from HL. The lymph node biopsy showed nodular sclerosis classic Hodgkin lymphoma. Therefore, CCL of HL and MF, with lymph node HL was diagnosed. The lesions of this patient responded to a sequential treatment to HL and MF. Being aware of this rare CCL facilitates correct diagnosis and proper clinical management.     

Folliculotropic mycosis fungoides in a psoriatic patient under methotrexate treatment

Folliculotropic mycosis fungoides is a variant of mycosis fungoides with a worse prognosis than the classic form. It can be associated with follicular mucinosis. We report a case of folliculotropic mycosis fungoides developing in the months following methotrexate therapy in a psoriatic patient. This lymphoma did not regress after stopping the antipsoriatic treatment. There is a known relationship between the use of immunosuppressive therapies and the development of lymphoproliferative malignancies. However these lymphomas are mainly B‐cell non‐Hodgkin lymphomas associated with Epstein‐Barr virus. In our patient the short period of time from the beginning of the immunosuppressive treatment to the occurrence of the T‐cell lymphoma does not support a strong causal relationship between the drug intake and the development of mycosis fungoides. To the best of our knowledge, this is the first case of folliculotropic mycosis fungoides in a patient treated with methotrexate for psoriasis.     

具有多种表现的蕈样肉芽肿1例

报告1例具有多种表现的蕈样肉芽肿。患者男,48岁。全身皮肤出现红斑、脱屑,并伴进行性皮肤松弛,四肢有斑块、破溃8年,秃发6个月。体格检查发现全身皮肤红斑,上覆大片状鳞屑和结痂;颈部两侧可见表皮松弛;四肢皮肤呈暗红色浸润的松弛性斑块和深在的溃疡;枕部头皮呈条片状胶质样秃发斑;颈项部、双上肢及胸部群集表面光亮的肤色丘疹和结节：左腹股沟可触及数个增大的淋巴结。诊断为蕈样肉芽肿,同时具有蕈样肉芽肿的多种表现：鱼鳞病样蕈样肉芽肿、肉芽肿性皮肤松弛症或肉芽肿性蕈样肉芽肿、毛囊性蕈样肉芽肿。     

Clinicopathological spectrum of mycosis fungoides

Cutaneous lymphomas represent a heterogeneous group of T-, NK- and B-cell neoplasms, with mycosis fungoides (MF) being the most common subtype. MF has a plethora of clinicopathological manifestations. Many variants of this lymphoma differ substantially from the 'classical' Alibert-Bazin disease and are therefore sometimes referred to as 'atypical' forms of the disease. This review addresses the whole clinicopathological spectrum of mycosis fungoides with respect to epidemiology, clinical, histopathological, immunophenotypic and genotypic features and the clinical course and prognosis of its variants: classical, erythrodermic, follicular, syringotropic, bullous/vesicular, granulomatous, poikilodermic, hypo- and hyperpigmented, unilesional, palmoplantar, hyperkeratotic/verrucous, vegetating/papillomatous, ichthyosiform, pigmented purpura-like, pustular and mucosal involvement in MF.     

Dyshidrotic mycosis fungoides

Mycosis fungoides (MF) represents the most common type of cutaneous T-cell lymphoma (CTCL). CTCL often progresses through patch, plaque and tumor stages but can also manifest with varied clinical presentations. MF rarely presents in vesiculobullous fashion, in which vesicles or bullae develop in pre-existing plaques or on the trunk or proximal extremities. We report a patient who presented with a vesiculobullous eruption on the palms and soles, resembling dyshidrotic dermatitis, which we believe represents dyshidrotic MF.     

儿童色素减退型蕈样肉芽肿一例并文献复习

报告儿童色素减退型蕈样肉芽肿一例并对相关文献进行复习。患儿,男,7岁。周身皮肤出现色素减退斑、红斑结痂1年,无明显瘙痒。组织病理检查：角层轻度角化,表皮轻度增生,可见淋巴样细胞亲表皮现象,真皮内可见团块状样细胞浸润。免疫组化示：CD3(+);CD20(个别+);CD21（-）;Ki-67（+10%）;CD2（+）;CD5（+）;CD7（+）;CD8（少许+）;CD4（+）。诊断：色素减退型蕈样肉芽肿。给予患儿NB-UVB治疗3个月皮损基本消退,目前维持治疗中。     

Concurrent mycosis fungoides and intravascular large B-cell lymphoma in a single patient

Mycosis fungoides (MF) is an indolent, uncommon, non-Hodgkin T-cell lymphoma of the skin. It classically presents with patches, plaques, and tumors and may rarely show spread to internal organs or bone marrow. Up to 7.5% of MF patients may be diagnosed with a second malignancy. Intravascular large B-cell lymphoma (IVLBCL) is an exceedingly rare non-Hodgkin B-cell lymphoma characterized by predominant growth of large neoplastic cells in the lumina of blood vessels. This case presents with an unusual confluence of two rare diagnoses, MF and IVLBCL, made more remarkable by the presence of both diagnoses on a single skin biopsy sample.     

Anetodermic mycosis fungoides: a new clinicopathological variant of mycosis fungoides

Mycosis fungoides is the most common type of primary cutaneous T-cell lymphoma. Several rare clinicopathological variants of mycosis fungoides have been described. Patients with these variants often also have classic mycosis fungoides at other sites of the body. Anetoderma is a cutaneous disorder in which multiple, oval lesions or atrophic plaques with wrinkled surface develop progressively due to loss of the dermal elastic tissue. Primary anetoderma occurs when there is no underlying associated disease and it arises on clinically normal skin, whereas secondary anetoderma appears in the same site as a previous specific skin lesion. There is a large list of heterogeneous dermatoses associated with secondary anetoderma. Two patients developed areas of secondary anetoderma on plaque stage lesions of mycosis fungoides. The lesions consisted of exophytic nodular lesions, with very soft consistency on palpation, scattered over the hyperpigmented plaques in one patient and violaceous indurated plaques with overlying epidermal atrophy and mild scale in the other. Histopathological study demonstrated that the cells involving the dermis were mainly T-helper lymphocytes, with few histiocytes and some multinucleate giant cells engulfing distorted elastic fibres. Elastic tissue stain demonstrated that elastic fibres were almost completely absent in the dermis of the anetodermic lesions. Anetodermic mycosis fungoides should be added to the list of clinicopathological variants of mycosis fungoides and mycosis fungoides should also be considered as a possible disease causing secondary anetoderma. Anetodermic mycosis fungoides shows clinical and histopathological features different from those of granulomatous slack skin.     

单一皮损蕈样肉芽肿一例

患者,男,50岁。右胸部红斑20余年。组织病理示：角化过度,棘层轻度增生,表皮内可见异型淋巴细胞,真皮浅层少量淋巴细胞浸润。免疫组化：CD3(+),CD4(+),CD5(+),CD8(+),CD7(+,丢失不明显),CD20(-),Ki67(表皮内个别淋巴细胞+)。T淋巴瘤克隆性基因重排检测结果：阳性。诊断为：蕈样肉芽肿(斑片期)。给予0.05%地奈德乳膏外用,4周后皮疹明显好转。     

Aggressive granulomatous mycosis fungoides with clinical pulmonary and thyroid involvement

We report a patient with granulomatous mycosis fungoides (MF) that progressed to a tumoral pattern and finally developed clinical pulmonary and thyroid involvement, despite multiple and intensive treatments. We emphasize the visceral involvement in this case, which was manifest as dyspnoea simulating pneumonia and by palpable thyroid nodules. These features are very unusual even in classic MF, and this is the first case in our knowledge of thyroid involvement in granulomatous MF.     

亲毛囊性蕈样肉芽肿一例

患者,男,28岁。全身瘙痒11年,头颈、躯干及双上肢红色丘疹、斑块伴嗜酸粒细胞增多5年,脱发2年。外周嗜酸粒细胞计数11 088/μL。组织病理示:毛囊周围中等量单一核细胞浸润,以不典型淋巴细胞为主,并见散在嗜酸粒细胞。免疫组化染色示浸润细胞主要是CD4+细胞。TCR基因重排示TCRδ、TCRγ均阳性。诊断:亲毛囊性蕈样肉芽肿。给予重组人干扰素α-2b肌注,阿维A、甲氨喋呤、泼尼松等口服,糖皮质激素软膏外用。治疗7周后皮损好转。     

Establishment of a mouse xenograft model for mycosis fungoides

Mycosis fungoides (MF) is the most frequent variant of cutaneous T-cell lymphomas (CTCLs). MF primarily involves the skin initially with patches and plaques. In later stages, cutaneous tumors develop and tumor cells may spread to lymph nodes and finally to visceral sites. Here, we describe an animal model for MF in immune-deficient nude mice, using the CTCL cell line MyLa. Subcutaneous transplantation of MyLa cells leads to the formation of cutaneous tumors in 80% of the mice (50/60 total). Spread of tumor cells to visceral sites was detected by immunohistochemistry and polymerase chain reaction (PCR)-based detection of specific T-cell receptor-gamma rearrangement. MyLa cells were found circulating in the blood, lymph nodes, and in blood vessels of heart, kidney, lung, and liver. In lung and liver tissue, tumor cells presented perivascular invasion, but no large secondary tumors developed. The nude mouse model described here will be a valuable test system for new therapeutic approaches for the treatment of MF and opens the unique opportunity to study the disease in vivo.     

Cardiac involvement and molecular staging in a fatal case of mycosis fungoides

Polymerase chain reaction (PCR) amplification of T-cell receptor-gamma gene rearrangement was used for molecular staging in a case of primary cutaneous T-cell lymphoma (CTCL) with fatal evolution. Although initial evaluation was negative for systemic involvement, the patient died due to heart failure. Autopsy findings revealed lymphomatous myocardial infiltration, but other tissues and organs examined, including lymph nodes, liver, spleen, lung and bone marrow, appeared to be free of disease. Molecular analysis from frozen samples obtained during the initial evaluation, as well as paraffin-embedded material obtained during autopsy, revealed the presence of clonal rearranged bands in all tissues examined except the bone marrow. Subsequent hybridization of PCR products with a tumour-specific oligoprobe confirmed the PCR results, suggesting widespread dissemination of the lymphomatous process. The use of molecular analysis can add significant information about the extent of disease in patients with CTCL and may be helpful in the establishment of therapeutic options.     

Annular hypopigmented mycosis fungoides: a novel ringed variant

Hypopigmented mycosis fungoides (MF) is a relatively uncommon variant of cutaneous lymphoma that is mostly seen in darker skin types. We present a novel and unique clinical presentation in an African-American female patient, consisting of regular hypopigmented annular rings in areas of normal skin and in more typical hypopigmented patches of MF. The lesions appeared diffusely on all extremities, anterior chest and back. Histopathologic examination showed an atypical lymphocytic infiltrate at the dermal-epidermal junction with epidermotropism and few Pautrier's collections. The patient was otherwise healthy and improved with narrowband ultraviolet (UV)-B. This case represents a presentation of a most unusual variant of hypopigmented MF, for which we propose the name 'annular hypopigmented MF'.     

Unilesional mycosis fungoides mimicking Bowen's disease

Cutaneous T-cell lymphoma includes a heterogeneous group of lymphomas that share the unique feature of T lymphocytes which are tropic to the skin. Clinically, the presentation of this disease is protean and can range from a single lesion to generalized erythroderma. Unilesional mycosis fungoides, a rare variant, is presented here. Its morphology mimicked squamous cell carcinoma in situ, and was refractory to conventional therapies. A review of the treatment of this subset is also presented.     

Transformed mycosis fungoides: clinicopathological features and outcome

BACKGROUND: Transformation of mycosis fungoides (T-MF) occurs in 8-55% of MF patients. Its early histopathological diagnosis is of tremendous importance to better define the management and to establish the prognosis. Recent studies have demonstrated that advanced-stage MF at diagnosis of transformation is the predominant risk factor of poor outcome. The 5-year survival rates for stage IIB and IV MF are 26.9% and 10.6%, respectively. The prognostic value of the immunophenotypic characterization of the infiltrate has not been thoroughly studied in the literature. OBJECTIVES: To retrieve clinical, histological and immunophenotypic features of T-MF in our patient population and analyse their prognostic value. PATIENTS AND METHODS: A register-based retrospective study was performed including all patients with cutaneous T-cell lymphoma (CTCL) registered in our two departments from January 2000 to December 2005. Among 208 patients with CTCL, 17 patients with proven transformation of their MF were studied. Clinical features and staging as well as immunophenotypic and pathological findings at the time of the initial diagnosis of MF and of the diagnosis of T-MF were analysed. RESULTS: Our results, in accordance with previously published material, indicate that the main clinical prognostic factor in T-MF is the stage of the initial disease at the time of the transformation. Patients with stage IIB-IV MF have a poor prognosis. In our study, strong expression of CD30 is linked to a better prognosis. CONCLUSIONS: We believe that pathological and immunopathological documentation of progressive MF is important in order to identify T-MF early; however, the differential diagnosis is sometimes difficult. Aside from already acknowledged prognostic factors such as older age, advanced initial disease and short delay to transformation, the CD30 immunophenotype could be regarded as a useful additional prognostic marker in T-MF.     

蕈样肉芽肿免疫表型分析及分子遗传学研究进展

 蕈样肉芽肿（MF）是最常见的原发皮肤T细胞淋巴瘤,临床上病程缓慢、迁延。MF肿瘤性T细胞最常见的免疫表型是 α/β T辅助细胞表型 (  βF1⁺、TCR-γ^-、CD3⁺、 CD4⁺、CD5⁺、CD8^-、CD45Ro⁺、TIA-1^-),占80%左右。但仍有一部分MF免疫表型很少见,如表达细胞毒性T细胞的标记(  CD8⁺, TIA-1⁺)、表达B细胞的标记（  CD20⁺）、表达间变大细胞的标记（  CD30⁺）、等,这些少见的免疫表型很容易与其它侵袭性较高的淋巴瘤相混淆,造成误诊、误治。本文对MF的免疫表型进行分析总结,并探讨其分子遗传学研究进展。