On-line version ISSN 1806-4841
An. Bras. Dermatol. vol.84 no.4 Rio de Janeiro July/Aug. 2009
Renato Soriani PaschoalI; Renata Nahas CardilliII; Darlene ArrudaIII; Belinda Pinto SimõesIV; Cacilda da Silva SouzaV
Physician, Division of Dermatology, Hospital das Clinicas de Ribeirao Preto,
Medical School, Ribeirao Preto, Universidade de São Paulo Ribeirao
Preto (SP), Brazil
IIOngoing graduate studies, Department of General Medicine and Assistant Physician, Division of Dermatology, Hospital das Clinicas de Ribeirao Preto, Medical School, Ribeirao Preto, Universidade de São Paulo Ribeirao Preto (SP), Brazil
IIIIn memoriam. Assistant Physician, Service of Pathology, Hospital das Clinicas de Ribeirao Preto, Medical School, Ribeirao Preto, Universidade de São Paulo Ribeirao Preto (SP), Brazil
IVPhD, Medical School, Ribeirao Preto, Universidade de São Paulo Ribeirao Preto (SP), Brazil
VPhD, Professor, Medical School, Ribeirao Preto, Universidade de São Paulo Ribeirao Preto (SP), Brazil
Subcutaneous panniculitis-like T-cell lymphoma is extremely rare and has recently been recognized as a clinicopathological entity. Young female, 17 years old, has complained of subcutaneous nodules and plaques in the limbs and abdomen for three years, accompanied of mild weight loss without other constitutional symptoms. Nodal, visceral and bone marrow involvement was absent, and subcutaneous CD3/CD8 atypical lymphocyte infiltration was observed in the skin sample. Chemotherapy interrupted the onset of new lesions and led to remission in the 8-month follow-up. Immunophenotypic and molecular aspects were relevant to the diagnosis and as prognosis makers.
Keywords: Immunohistochemistry; Lymphoma, non-Hodgkin; Panniculitis
Primary cutaneous T-cell lymphomas (CTCL) comprise a group of Non-Hodgkin lymphoma (NHL) with heterogeneous clinical and biological characteristics. They are defined as clonal malignant proliferation of T lymphocytes or natural killer cells (NK) that reside on the skin 1-4. The current WHO classification for CTCL includes 13 entities. Fungoid mycosis and its variations, Sezary syndrome, anaplastic large cell cutaneous lymphoma and lymphomatoid papullosis represent approximately 95% of all CTCL 1,4.
Panniculitis-like T-cell lymphoma (PLTCL) is an uncommon type of CTCL which was recognized as a clinical-pathological entity only in 1991. Up to 2003, there were fewer than 200 cases reported in the English-speaking literature. The neoplasm affects both adults and children, and both genders 5. Clinically, it is characterized by nodules or erythematous and infiltrate plaques, rarely ulcerated, solitary or multiple, involving mainly the extremities, or generalized, involving other regions as well 5. Systemic manifestations such as fever, weight loss and fatigue may be present. Clinical course may be prolonged, with occasional spontaneous regression of skin lesions, or rapidly progressive and fatal, despite aggressive chemotherapy. As the latter manifestation, PLTCL is frequently associated with hemophagocytic syndrome 5,6. Histopathology is characterized by panniculitis-like pattern, with neoplastic involvement of subcutaneous tissue. This infiltration of the subcutaneous region by pleomorphic T-cells and benign macrophages mimic lobular panniculitis. Involvement of the dermis may also be observed, but in general the extension of the dermal invasion is minimal, and involvement of the epidermis is very rare. Mixed proliferation of atypical lymphocytes is more commonly formed by large cells intertwined with medium and/or small cells. Malignant cells are predominantly cytotoxic T cells with expression of αβ, or γδ of T cell receptors (TCR) 6.
Nonspecific clinical manifestations of PLTCL may hinder and postpone the diagnosis and histopathological and immunohistochemical exams are essential to that end. Nodous erythema and panniculitis with different etiopathogenesis are their main differential diagnoses. However, given that it is rare, prognostic analysis and definition of the best management approach are difficult for the clinician.
We reported a case of a young female patient, with diagnostic difficulties, dermatological, histopathological and immunohistochemical aspects of PLTCL, and disease remission when undergoing anthracycline-based chemotherapy.
Female 17-year-old patient, previously healthy, with erythematous to purplish nodous associated with atrophic depressions located on the limbs and abdomen (Figure 1) for three years. She reported previous investigation and therapy for nodous erythema without success. She reported non-quantified weight loss but no fever or other general symptoms. The physical examination did not show adenomegalia, hepatosplenomegalia and other abnormalities. The lab test results (complete blood count, urine analysis I, renal function, liver enzymes, anti-nucleus factor [ANF], and protein electrophoresis) did not show any affection. Serology for hepatitis B, C and syphilis, bacilloscopy and anti-glicophospholipid-1 dosing (PGL-1) were negative. Montenegro and Mitsuda reactions were negative, as well as fungi and mycobacteria cultures of skin lesion fragments. As to skin histopathology, in the deep dermis and subcutaneous cell tissue, there was dense inflammatory lymphohistiocytarian infiltrate comprising frequent atypical lymphocytes, small to intermediate in size, organized in planes that comprised septae and lobules and formed ringed-figures around the adipocytes (Figure 2). Immunohistochemistry showed positive labeling for CD3/CD8 and TIA-1 in most neoplastic cells, and negative for anti-CD20, CD56 and EBV. There was weak co-expression for CD4 in part of the population of neoplastic-cells and rare cells were positive for CD30 (Figure 3). Serology for HTLV-1, HTLV-2 and EBV were negative. Bone marrow biopsy did not show medullar infiltration by neoplastic cells. Computed tomography scan (CT scan) of the neck, chest and abdominal region did not identify nodal or visceral affection, but they only confirmed the cutaneous nodous on the abdomen. The patient was staged as T3N0M0 (IIB) and treated with CHOP 14 regimen, comprising cyclophosphamide, adriamycin, vincristin and prednisone, with filgrastim (G-CSF) on days 4 to 14, associated with intrathecal methotrexate before each cycle of polychemotherapy. On the 2nd cycle, the patient no longer reported the onset of new lesions and reported subjective remission of existing lesions. After four cycles of polychemotherapy, a new skin biopsy identified infiltration of atypical lymphocytes in subcutaneous fatty tissue with the same immunohistochemical pattern. The patient underwent four additional cycles of chemotherapy and complemented eight cycles. At the end of these cycles, the interruption of new lesions was confirmed by clinical examination, where we detected few lesions of residual aspect associated with hyperchromic spots and atrophic depressions on the limbs and abdomen.
New neck, chest and abdominal CT scan showed absence of adenomegalia and reduction of diameter of the abdominal cutaneous nodous. Histopathological examination of residual lesions showed fibrosis of subcutaneous fatty tissue in the lobular and septal region with minimum foci of perivascular lymphohistiocytarian infiltrate with atypia. The disease was considered in remission and we decided for strict clinical follow up of the patient, which has already completed 8 months after chemotherapy.
PLTCL affects predominantly young adults, mean age of approximately two decades, when compared to the mean age of patients with other types of primary cutaneous T-cell lymphomas, in agreement with the present case. A broad review and systematic analysis of 156 cases in the literature, carried out by Go and Wester in 2004, showed that the mean age at diagnosis was 39 years, ranging from 0.5 to 84 years and 75% of the patients were aged between 18 and 60 years of age 6.
This review confirmed relevant information about the scarcity of cases reported in the literature. The authors identified: the presence of hemophagocytic syndrome and the expression of TCRγδ by tumor cells at diagnosis as being associated with the prognosis; mean survival of 2 years; anthracycline-base chemotherapy or high doses of chemotherapy and subsequent stem cell transplantation among the best therapeutic options 6-9.
The significant finding of number of neoplastic cells with TCRγδ expression above 30%, in which there was only 7% of normal T-cells, is consistent enough to be considered as representative phenotype of PLTCL. 5,6 In addition, clonal rearrangement of TCR was detected in 85% of the patients 6.
Natural history of PLTCL frequently has an aggressive course, resulting in almost 50% disease-related mortality and mean survival of 2 years. The protruded pattern may be temporary and it frequently evolves to more aggressive disease. However, there may be chronic and indolent progression that lasts for years and there is rare spontaneous remission of the disease 6.
There is agreement in the literature about the two groups of PLTCL, whose distinct histological and immunophenotypical patterns and the prognosis could differentiate them. Cases with T cell of a phenotype are normally CD8 positive and restricted to subcutaneous tissue, with dermal and epidermal involvement and they are frequently of indolent clinical course. Conversely, PLTCL with T cell κd phenotype approximately 25% of the cases are typically CD4 and CD8 negative, and frequently co-express CD56. This latter group, whose neoplastic infiltrate is not confined to subcutaneous tissue and involves the adjacent dermis and epidermis, invariably has poor prognosis 5,6,7.
The prolonged investigation period of about three years and the previous diagnosis in the present case confirmed the difficult to diagnose those cases. However, the absence of systemic manifestations and nodal and visceral involvement is in agreement with the rare dissemination to extracutaneous sites shown in the literature. The disease presenting less aggressive pattern and chronic and indolent progression seems to comprise the minority of cases shown in the literature or it consists of the transient phase of the disease 5. Despite the period of about three years without specific treatment, once staging T3N0M0 IIB was made, the proposed treatment resulted in no more new lesions, and only fibrosis with absence of atypical lymphocytes was shown in the histopathological exam of residual lesions. In the short follow-up of eight months, remission of the disease has been maintained, confirming the success of the therapeutic regimen with anthracycline-based chemotherapy. The authors suggested that the absence of poor prognosis factors would be directly related with the progression pattern and the therapeutic response in the case and reinforced the rarity and the inclusion of PLTCL in the differential diagnosis of panniculitis.
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Profa. Dra. Cacilda da Silva Souza
Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto USP
Av. Bandeirantes, 3900 Monte Alegre
CEP: 14048-900 - Ribeirão Preto - SP
Tel./fax: 16 3602-2716 16 3633-0236
Recebido em 22.08.2008.
Aprovado pelo Conselho Editorial e aceito para publicação em 30.10.2008.
Conflict of interest:
Financial funding: Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto Universidade de São Paulo.
How to cite this article: Paschoal RS, Cardilli RN, Arruda D, Simões BP, Souza CS. Linfoma Subcutâneo de Células T Paniculite-Símile. An Bras Dermatol. 2009;84(4):415-9.