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  Table of Contents    
ORIGINAL ARTICLE  
Year : 2011  |  Volume : 54  |  Issue : 2  |  Page : 318-322
Subcutaneous panniculitis-like T-cell lymphoma: A clinicopathologic study of 5 cases


1 Department of Medical Oncology, Dr. BRA Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
2 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
3 All India Institute of Medical Sciences, New Delhi, India
4 Department of Dermatology, All India Institute of Medical Sciences, New Delhi, India

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Date of Web Publication27-May-2011
 

   Abstract 

Background: Subcutaneous panniculitis-like T-cell lymphoma is as yet a poorly characterized subtype of cutaneous T-cell lymphomas. It is difficult to diagnose and lacks a standard treatment protocol. Materials and Methods: We report our experience with five such cases in patients with age ranging from 13 to 45 years, wherein we reviewed their clinical presentations, histopathological findings, treatment and clinical outcome. Results: Three out of the five cases are alive of which two are in complete remission. Our series stresses on the need to be aware of this uncommon entity in a dermatology clinic. Facial and upper extremity skin nodules with involvement of the lower dermis on light microscopical examination and suggestive immunohistochemical findings were frequently observed in our patients in contrast to previously described cases.

Keywords: Cutaneous lymphoma, panniculitis-like lymphoma, T-cell lymphoma

How to cite this article:
Bakhshi S, Das P, Puri K, Singhal M, Ramam M, Sharma A, Iyer VK, Gupta SD. Subcutaneous panniculitis-like T-cell lymphoma: A clinicopathologic study of 5 cases. Indian J Pathol Microbiol 2011;54:318-22

How to cite this URL:
Bakhshi S, Das P, Puri K, Singhal M, Ramam M, Sharma A, Iyer VK, Gupta SD. Subcutaneous panniculitis-like T-cell lymphoma: A clinicopathologic study of 5 cases. Indian J Pathol Microbiol [serial online] 2011 [cited 2019 Dec 11];54:318-22. Available from: http://www.ijpmonline.org/text.asp?2011/54/2/318/81614



   Introduction Top


Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cutaneous lymphoma of alpha/beta T-cell origin, that preferentially infiltrates the subcutaneous adipose tissue and is categorized under the mature T-cell and natural killer (NK)-cell lymphomas in 2008 WHO/EORTC classification of cutaneous lymphomas. [1] It typically presents as subcutaneous nodules that may ulcerate and is often associated with fever, hepatosplenomegaly, mucosal ulcers as well as serosal effusions. [2],[3],[4] SPTCL has been given an independent status as a distinct clinicopathologic entity in the WHO classification. [1] It may follow an indolent waxing and waning course, with no constitutional symptoms and often spontaneous regression of skin lesions (cytophagic histiocytic panniculitis). [5],[6] In addition, it may follow a rapidly progressive and eventually fatal course, which is often secondary to the hemophagocytic syndrome in which biopsies of the affected organs reveal histiocytes engulfing and entrapping the hematopoietic cells. [7]

Histologically, SPTCL is characterized by an infiltrate composed predominantly of atypical lymphocytes and histiocytes. Extensive tumor necrosis, karyorrhectic debris along with cytophagocytosis and angioinvasion characterize this disease. Apoptotic mechanisms are known to be involved in its pathogenesis. [1],[2],[5],[8],[9],[10],[11] With a fewer than 200 cases reported in the English-language literature since 1991, it is as yet a poorly characterized subtype of cutaneous T-cell lymphomas, difficult to diagnose and lacks a standard treatment protocol. Given the sparse data, especially from the Indian subcontinent, the objective of this study was to characterize the clinical presentation, histopathological features, treatment response and treatment outcome in patients with SPTCL diagnosed at our center. [12],[13]


   Materials and Methods Top


We reviewed the cases of SPTCL diagnosed and treated at our institute since January 2004 to June 2008 and analyzed their clinical presentations, histomorphological findings in detail by two pathologist blinded about the diagnosis. The biopsy slides of skin nodule, bone marrow and other organs as available were reviewed.

Immunohistochemical stains were performed for LCA (Novocastra, Newcastle, UK; 1:100) CD20 (Novocastra, Newcastle, UK; 1:200), CD3 (Novocastra, Newcastle, UK; 1:150), CD4 (Novocastra, Newcastle, UK; 1:10 [Citrate pH 8]), CD8 (Novocastra, Newcastle, UK; 1:100), CD68 (BioSB, CA, USA; 1:1000), CD30 (BioSB, CA, USA; 1:200), CD15 (DBS, CA, USA; 1:100) and CD56 (Novocastra, Newcastle, UK; 1:200) in the appropriate dilutions of the primary antibodies as mentioned. Citrate buffer with pH 6 was used for antigen retrieval in microwave oven for 30 minutes. The ultravision detection system of Thermo-Scientific, CA, USA was used for the stain development. An overnight IHC protocol was followed as already standardized in our institute. The pattern of positivity was analyzed. Data were also collected regarding other diagnostic work-up, therapy and outcome.


   Results Top


Clinical

Out of the five patients, there were three females and two males, with an age range of 13-45 years and duration of illness at presentation varying from 2 to 60 months [Table 1]. All of them presented with indurated, non-tender, non-ulcerated skin lesions of 1-5 cm in diameter in various parts of the body. Four out of five patients presented with one or more of the B symptoms. Lymphadenopathy, though small was detected in two patients and in both lymph node biopsies were taken. Contrast-enhanced computed tomography (CECT) of chest and abdomen showed presence of nodules in the chest, liver and spleen in one of the patients; fine needle aspiration cytology from these nodules was however inconclusive as the material yield was small. Three patients were detected to have hepatosplenomegaly but there were no evidence of infiltrative lesion in the form of nodules or hypodense lesions as detected by radiological procedures. While after applying therapeutic regimens, three patients showed complete response, one of them had partial response and one was lost to follow-up.
Table 1: Clinical profile of cases

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Histopathology

A total of seven skin biopsies, two from lymph node and five bone marrow biopsies of the five index cases were reviewed [Table 2]. Histologically in all skin biopsies there was a predominant .subcutaneous infiltrate of atypical lymphoid cells with an extension of the infiltrate in the lower dermis [Figure 1]a,b. Light microscopy showed infiltration pattern in the subcutaneous fat resembling a septo-lobular panniculitis [Figure 1]b. In, three out of seven biopsies examined, the infiltrate was confined to the subcutaneous location only. The infiltrate predominantly comprised of immature lymphoid mononuclear cells and foamy macrophages. Macrophages were found to be a consistent inhabitant of these lesions and in our cases, the range of macrophage infiltration varied from 10 to 60% out of the total burden of infiltrate [Figure 1]c,d. Morphologically the macrophages showed foamy to ground glass eosinophilic cytoplasm with engulfed cellular debris [Figure 1]c. In most of our cases the infiltrating lymphoid cell population was small to intermediate in size [Figure 1]d. However the pattern of distribution of these atypical lymphoid cells was unpredictable and did not follow a definite pattern. For example in patients in whom biopsies were taken from two different nodules (patients 2 and 3), the lympho-cytomorphological atypia varied in different locations. In five biopsies the pattern of infiltration was predominantly lobular, while it was exclusively lobular and both septal and lobular in one patient each.
Figure 1: Photomicrograph shows epidermis and the upper half of the dermis in a case of SPTCL showing minimal histological changes (a, H and E ×40). The cellular infiltrate is restricted to the subcutaneous fat with a septo-lobular pattern of involvement (b, H and E ×100). The cellular infiltrate predominantly comprising of histiocytes and atypical lymphoid cells (c and d; c, H and E, ×100; d, H and E ×400. In addition there are a few large vacuolated foam cells with engulfed cellular debris, called 'bean bag cells (d (inset), H and E ×400). Presence of multinucleated cells, some of which resembled Langhan's cells (arrow) was identified amidst the cellular infiltrate (e, H and E ×100). Focal vasculitis (f [inset], H and E ×200) and subcutaneous fat necrosis are noted (f, H and E, ×40). Well-defined epithelioid cell granulomas (arrow) and lining of the fat spaces by the atypical lymphoid cells were identified (g, H and E, ×200). Immunohistochemical stains show string membranous CD3 positivity of the infiltrating cells (h, IHC [CD3] ×100). CD56 stain was consistently negative in the infiltrating lymphoid cells (i, IHC [CD56] ×40); while positive control for CD56 shows strong positivity (i [inset], IHC [CD56] ×40).

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Table 2: Histopathology characteristics of skin biopsies of patients with subcutaneous panniculitis-like T-cell lymphoma (7 biopsies in 5 cases)

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A consistent finding was rimming of individual adipocytes by atypical lymphoid cells [Figure 1]d. The macrophages frequently showed evidence of hemophagocytosis locally within the subcutaneous infiltrate. Another very characteristic finding was the large foamy histiocyte containing fat droplets, cell fragments and nuclear debris - the 'bean bag' cell [[Figure 1]d [inset]]. Though giant cell transformation was a frequent finding, epithelioid granulomas could be identified in two biopsies around the infiltrate, one of which showed frank necrotic material and the other fibrinoid material [Figure 1]e-g. At places, the lymphoid cells were seen to infiltrate the wall of subcutaneous arterioles with focal fibrinoid necrosis along with surrounding necrosis and numerous apoptotic bodies and karyorrhectic debris [[Figure 1]f and 1f [inset]]. A few plasma cells and occasional neutrophils were also noted within the lesions, ranging from 2 to 3% of the total cell population. Eosinophils were consistently absent. None of the bone marrow or lymph node biopsies showed evidence of hemophagocytosis. As well there was no evidence of bone marrow infiltration by the atypical lymphoid cells in any of the cases. The lymph node biopsies showed reactive follicular hyperplasia with sinus histiocytosis. Relative increase of bone marrow eosinophils was noted in one case [Table 1]. The immature lymphoid cells were strongly immunopositive for leukocyte common antigen (LCA), CD3 and CD8 [Figure 1]h. The macrophages were strongly positive for CD68. The lymphoid cells were negative for CD20, CD4, CD30, CD15 as well as for CD56 [Figure 1]i (positive control for CD56). Only a single case showed an occasional scattered NK cells [Table 2].

Outcome

Four of five patients received therapy, with complete response in three of them and partial response in one. Two patients received only steroids, one received 6 cycles of CHOP and another was treated with BFM-90 protocol [Table 1]. [14] All these four treated patients relapsed at 4.5-21 months after achieving remission. Of the four relapsed patients, interestingly one patient who relapsed as a plaque-like lesion in the thigh subsided spontaneously (case 1); one was lost to follow-up without any therapy (case 4); one responded to salvage chemotherapy (case 5), while the other one did not respond with salvage chemotherapy (case 1).


   Discussion Top


SPTCL has been recognized since 1997 and was included as a distinct entity since 2001 WHO/EORTC classification of hematolymphoid classification; in 2008 WHO classification it continues to be recognized as a separate entity . [1] It accounts for less than 1% of all non-Hodgkin lymphomas. Mostly a malignancy of young adults, it has also been evidenced in a systematic analysis of 156 patients, in whom the median age at diagnosis was 39 years. [3] In our series, all patients were less than 45 years of age with a median age of 20 years.

Presentation of this disease is mostly at a dermatology clinic, with multiple asymptomatic subcutaneous nodules and plaques, predominantly affecting the legs or trunk, and less commonly the faces or arms. [2] Ulcerative lesions were reported in a previous report as well. [1] In the index cases the skin lesions were varying from 1 cm to 5 cm in size and were asymptomatic in all five of them with no ulceration. Lower extremities and trunk were involved in four cases each. Notably, 3/5 cases also showed facial and upper extremity involvement. In literatures the most common described site is the lower extremities and trunk. [1] Four of our patients presented with fever, with two of them also manifesting night sweats and weight loss. Of the four patients with systemic complaints, hepatomegaly was present in three cases along with splenomegaly in two of them. The systemic complication of the cytokine release and the associated hemophagocytic syndrome in these patients may be a cause. [1] Though one of the patients had pancytopenia, hemophagocytosis was not detected in any patient either in bone marrow or lymph node biopsies. However, in three out of five patients there were localized hemophagocytosis in the skin biopsies itself without any systemic involvement. In other series systemic hemophagocytic syndrome has been identified in 15-20% cases. [1]

As a differential diagnosis of this lesion, any cutaneous neoplasm expressing T-cell and NK-cell markers can be considered, which include primary cutaneous γ/δ T-cell lymphoma, extra-nodal NK/T cell lymphoma, primary cutaneous anaplastic large cell lymphoma, mycosis fungoides and blastic plasmacytoid neoplasms. [1] Based on the morphology it is difficult to differentiate SPTCL from primary cutaneous α/δ T-cell lymphoma and extranodal NK/T cell lymphomas. Extra-nodal /∞ T/NK cell lymphoma, in contrast to SPTCL, invades the epidermis and dermis; in addition to expression of NK cell they are CD3- and CD56+. These cases are almost invariably associated with EBV infection of the tumor cells. In our study, exclusive subcutaneous involvement was seen in only one patient, while in four other patients in addition to the subcutaneous involvement there were focal lower dermal spread, in contrast to the previous reports of dermal sparing. The proportion of the atypical lymphoid cells and macrophages in our series show consistency with the previous reports. [3],[8] Areas of vascular invasion by the atypical lymphoid cells, necrosis, karyorrhexis and epithelioid cell granulomas were also described previously. [1],[2],[5] The angiocentricity by the atypical T lymphocytes result in vasculitis, thrombus formation and ischemic necrosis of the subcutaneous fat and degeneration of the tumor cells.

Based on TCR gene expression, there are two subtypes of SPTCL: α/β and γ/δ. It is mostly sporadic, though there has been some evidence of immunosuppression being a predisposing factor for the γ/δ phenotype of SPTCL. Recently in the WHO classification of cutaneous lymphomas, it was suggested that only the α/δ subtype of this disease be regarded as SPTCL, and that the γ/δ be regarded as a separate entity. [15] In our cases, further studies for T-cell receptor gene rearrangement could not be done due to ack of facilities for the same. However the expression of CD8 cytotoxic T-cell marker, lack of NK cell immuno-phenotype and preferential involvement of the subcutaneous fat and only lower dermis indicates towards a possible α/β T-cell phenotype in our cases. It has to be remembered that though in γ/δ T-cell lymphoma both CD4 and CD8 markers are negative, occasionally CD8 can be expressed; however, the CD56 is consistently negative in these cases. [1] Cutaneous ALCL and mycosis fungoides do not automatically come in differential diagnosis of the index cases.

In a previous analysis of SPTCL, prednisone was used frequently as the initial therapy in patients who had less aggressive disease at presentation but durable complete remission was infrequently achieved. Anthracycline-based chemotherapy regimens were most commonly used and most effective systemic treatment options, producing long-term CR in about 30% patients. After median follow-up of 24 months, 48% of patients died of disease; median survival duration was 27 months. [10] In our series, the two patients treated with anthracycline-based regimens relapsed but one of them subsided spontaneously, which again shows the diverse behavior of this disease. Both cases treated with steroids alone also recurred, one of whom was again achiever CR on follow-up after chemotherapy. Thus, the more appropriate options between the two cannot be derived from this series and need studies with larger numbers of SPTCL.

However the main obstacle in understanding this disease is its infrequency. We could only identify five cases in four years; whereas in the same time period there were approximately 1000 cases of NHL registered at our center of which there were 90 patients with peripheral T-cell lymphoma. Thus, this series adds valuable information to enrich our knowledge about this rare entity. Much understanding of this disease entity is a must as distinction from cutaneous γ/δ T-cell lymphoma or NK/T-cell lymphomas are needed as the latter show dismal prognosis.

 
   References Top

1.Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (4 th ed). Lyon, France: IARC Press; 2008. p. 294-95.  Back to cited text no. 1
    
2.Hoque SR, Child FJ, Whittaker SJ, Ferreira S, Orchard G, Jenner K, et al. SPTCL: A clinicopathologic, immunophenotypic and molecular analysis of six patients Br J Dermatol 2003;148:516-25.  Back to cited text no. 2
    
3.Wang L, Yang Y, Liu W, Liao Q, Lai R, Li F, et al. SPTCL: Expression of cytotoxic-granule associated protein TIA-1 and its relation with Ebstein-Barr virus infection. Zhonghua Bing Li Xeu Za Zhi 2000;29:103-6.  Back to cited text no. 3
    
4.Go RS, Wester AM. Immunophenotypic and molecular features, clinical outcomes, treatments and prognostic factors associated with subcutaneous panniculitis-like T-cell lymphoma. Cancer 2004;101:1404-13.  Back to cited text no. 4
    
5.Salhany KE, Macon WR, Choi JK, Elenitsas R, Lessin SR, Felgar RE, et al. Subcutaneous panniculitis-like T-cell lymphoma: Clinicopathologic, immunophenotypic and genotypic analysis of alpha/beta and gamma/delta subtypes. Am J Surg Pathol 1998;22:881-93.  Back to cited text no. 5
    
6.Perniciaro C, Zalla MJ, White JW Jr, Menke DM. Subcutaneous panniculitis-like T-cell lymphoma: Report of two additional cases and further observations. Arch Dermatol 1993;129:1171-6.  Back to cited text no. 6
    
7.Weenig RH, Ng CS, Pernicaro C. Subcutaneous panniculitis like-T-cell lymphoma. Am J Dermatopathol 2001;23:206-15.  Back to cited text no. 7
    
8.Kumar S, Krenacs L, Medeiros J, Elenitoba-Johnson KS, Greiner TC, Sorbara L, et al. Subcutaneous panniculitic T-cell lymphoma is a tumor of cytotoxic T lymphocytes. Hum Pathol 1998;29:397-403.  Back to cited text no. 8
    
9.Willemze R, Jansen PM, Cerroni L, Berti E, Santucci M, Assaf C, et al. Subcutaneous panniculitis-like T-cell lymphoma: Definition, classification, and prognostic factors: An EORTC Cutaneous Lymphoma Group Study of 83 cases. Blood 2008;111:838-45.   Back to cited text no. 9
    
10.Al Zolibani AA, Al Robaee AA, Qureshi MG, Al Nosian H. Subcutaneous panniculitis-like T-cell lymphoma with hemophagocytic syndrome successfully treated with cyclosporin A. Skinmed 2006;5:195-7.  Back to cited text no. 10
    
11.Marzano AV, Berti E, Paulli M, Caputo R. Cytophagic histiocytic panniculitis and subcutaneous panniculitis-like T-cell lymphoma: Report of 7 cases. Arch Dermatol 2000;136:889-96.  Back to cited text no. 11
    
12.Singh A, Kumar J, Kapur S, Ramesh V. Subcutaneous panniculitis-like T-cell cutaneous lymphoma. Indian J Dermatol Venereol Leprol 2008;74:151-3.  Back to cited text no. 12
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13.Medhi K, Kumar R, Rishi A, Kumar L, Bakhshi S. Subcutaneous panniculitis like T-cell lymphoma with hemophagocytosis: Complete remission with BFM-90 protocol. J Pediatr Hematol Oncol 2008;30:558-61.  Back to cited text no. 13
    
14.Seidemann K, Tiemann M, Schrappe M, Yakisan E, Simonitsch I, Janka-Schaub G, et al. Short-pulse B-non-Hodgkin lymphoma-type chemotherapy is efficacious treatment for pediatric anaplastic large cell lymphoma: A report of the Berlin-Frankfurt-Münster Group Trial NHL-BFM 90. Blood 2001;97:3699-706.   Back to cited text no. 14
    
15.Willemze R, Jaffe ES, Burg G, Cerroni L, Berti E, Swerdlow SH, et al. WHO-EORTC classification for cutaneous lymphomas. Blood 2005;105:3768-85.  Back to cited text no. 15
    

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Correspondence Address:
Sameer Bakhshi
Department of Medical Oncology, Dr. BRA Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi - 29
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.81614

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