This is a variant of a peripheral T-cell lymphoma characterized by multiple subcutaneous nodules with fever, hepatosplenomegaly, mucosal ulcers, and serosal effusions. Biopsies of affected organs reveal extensive hemorrhage and histiocytes phagocytizing red blood cells. The disease ranges from an indolent form which has sometimes been referred to as cytophagic histiocytic panniculitis (CHP) to a frankly malignant T-cell lymphoma. Most investigators believe that there is a spectrum of the disease with the so-called benign variant a subclinical lymphoid malignancy that may not manifest until years later. This concept is complicated by the fact that severe infections with agents as varied as adenovirus, Brucella, and Trichosporon species may produce a syndrome known as infection-associated hemophagocytic syndrome (IAHS), a syndrome with a similar clincal and histologic presentation as cases of CHP. It is possible that cases of IAHS may have been lumped into cases of CHP in the past, confusing the clinical course of these patients. It is currently recommended that CHP not be used and all cases are identified as a T-cell lymphoma so that appropriate therapy may be instituted.
Epidemiology Disease Associations Pathogenesis Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/
Differential Diagnosis Prognosis Treatment Commonly Used Terms Internet Links
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS Cytophagic histiocytic panniculitis INCIDENCE Very rare EPIDEMIOLOGIC ASSOCIATIONS Epstein-Barr virus
Latent infection has been detected but not in cases of CHP
In situ hybridization for EBV RNA has been negative in all cases
DISEASE ASSOCIATIONS CHARACTERIZATION HEMOPHAGOCYTIC SYNDROME Clinical-pathologic condition, not unique to this disease, characterized by massive hemorhage in organs, especially liver and spleen, and histologically by histiocytes with erythrophagocytosis TRANSPLANT, ORGAN
- Subcutaneous panniculitic T-cell lymphoma in a cardiac allograft recipient.
Bregman SG, Yeaney GA, Greig BW, Vnencak-Jones CL, Hamilton KS.
Department of Pathology, Vanderbilt University Medical Cente, Nashville, TN, USA.
J Cutan Pathol. 2005 May;32(5):366-70. Abstract quote
Background: Post-transplant lymphoproliferative disorder (PTLD) is the third leading cause of death in heart transplant patients beyond the immediate peri-operative period (Ouseph R, Denny DM, Erbeck KM. J Am Soc Echocardiogr 1998; 11: 758; Armitage JM, Kormos RL, Stuart RS, et al. J Heart Lung Transplant 1991; 10: 877; Swinnen LJ, Mullen M, Carr TJ, et al. Blood 1995; 86: 3333; Ying AJ, Myerowitz D, Marsh WL. Ann Thorac Surg 1997; 64: 1822). The majority of PTLD cases are of B-cell origin whereas T-cell neoplasms have been reported as rare, aggressive, and late complications of solid-organ transplantation (Fatio R, Sutsch G, Mayer K, et al. Transplant Proc 1998; 30: 1118).
Case report: A 50-year-old cardiac allograft heart transplant patient presented with subcutaneous nodules involving his trunk and extremities.
Results: Light microscopy revealed features characteristic of subcutaneous panniculitic-like T-cell lymphoma. Immunohistochemical analysis showed expression for CD45RO, TIA-1, and focal CD3 positivity by tumor cells. Flow cytometry performed on a subsequent subcutaneous nodule demonstrated an abnormal T-cell population with expression of CD3, CD8, CD56, and T-cell receptor alpha-beta, and no expression of CD4. T-cell gene rearrangement studies revealed a clonal population of cells with a bi-allelic gene rearrangement.
Conclusion: We report a case of an unusual subtype of PTLD in a cardiac allograft recipient.
PATHOGENESIS CHARACTERIZATION GENERAL Clonal proliferation of T cells Show T cell receptor gene rearrangement for the gamma receptor APOPTOSIS
Apoptosis and proliferation in subcutaneous panniculitis-like T-cell lymphoma.
Sen F, Rassidakis GZ, Jones D, Jeffrey Medeiros L.
Division of Pathology and Laboratory Medicine, University of Texas, MD Anderson Cancer Center, Houston, Texas.
Mod Pathol 2002 Jun;15(6):625-31 Abstract quote
Subcutaneous panniculitis-like T cell lymphoma (SPTCL), designated recently as a distinct clinicopathologic entity in the World Health Organization Classification, is a neoplasm composed of cytotoxic T-cells that preferentially involves subcutaneous adipose tissue. Histologically, SPTCL is characterized by extensive karyorrhectic debris and tumor necrosis suggesting that apoptotic mechanisms are involved in its pathogenesis.
We assessed the apoptotic index (AI) and proliferation rate (PR) of 13 cases of SPTCL by TUNEL test and Ki-67 immunostaining, respectively. We also immunohistochemically assessed for expression of BCL-2 (anti-apoptosis), BAX (pro-apoptosis), and P53 and correlated the results with apoptosis and proliferation. We detected a high AI (median 8.1%) in 11 cases of SPTCL, and 12 cases had low BCL-2 and high BAX expression. BCL-2 expression inversely correlated with AI (P <.001) and BAX (P <.001). We found a low PR (cutoff >/= 25%) in eight (61%) cases. There was an inverse correlation between AI and PR (r = -.58, P =.04). Ten cases were assessed for P53; immunostaining results were heterogeneous but P53 expression correlated with large cell cytologic features.
Our findings demonstrate that SPTCLs have a high AI that may be explained by differential expression of BCL-2 and BAX in the neoplastic cells.
CHARACTERIZATION DIC Peripheral cytopenia
CHARACTERIZATION General May be two clinical presentations Protracted CHP-like phase Indolent smoldering disease which may or may not lead to death Rapidly progressive course Usually leads to death
- Fatal Subcutaneous Panniculitis-Like T-Cell Lymphoma gamma/delta Subtype (Cutaneous gamma/delta T-Cell Lymphoma): Report of a Case and Review of the Literature.
From the *Department of Pathology & Laboratory Medicine, Baltimore Veterans Affairs Medical Center, Baltimore, Maryland; daggerDepartment of Dermatology, George Washington University School of Medicine, Washington, DC; and Departments of double daggerDermatology; section signPathology; and paragraph signMedicine, University of Maryland, Baltimore, MD.
- Am J Dermatopathol. 2008 Dec;30(6):593-599. Abstract quote
Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a distinct type of peripheral T-cell lymphoma, which has gained recognition over the past decade. The disease presents complex clinical, pathologic, and immunohistochemical features, which warrant awareness by dermatologists, dermatopathologists, hematopathologists, hematologists, oncologists, and internists. SPTCL was initially included as a provisional entity in the Revised European-American Lymphoma classification, followed by the European Organization for Research and Treatment of Cancer classification as a primary cutaneous lymphoma, and subsequently as a distinct entity by the World Health Organization classification.
It is known that patients diagnosed with SPTCL usually respond poorly to therapy, and the tumor progresses aggressively. Data from recent studies in a series of cases of SPTCL by the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Group have further identified SPTCL as a heterogeneous disease entity, which comprises an alpha/beta subtype (SPTCL-AB) and a gamma/delta subtype (SPTCL-GD). The latter has recently been included in the entity of "cutaneous gamma/delta T-cell lymphoma" by the World Health Organization, Pathology and Genetics of Skin Tumours.
The clinical, histologic, and immunophenotypic data, treatment, and prognosis, appear different in the 2 subtypes of SPTCL.
We report a case of fatal SPTCL-GD (cutaneous gamma/delta T-cell lymphoma), with detailed clinicopathologic features, immunohistochemical studies, treatment, and clinical course. In view of its aggressive behavior, identification of this disease is critical for proper management and treatment.
- Subcutaneous panniculitis-like T-cell lymphoma: a clinicopathologic, immunophenotypic, and molecular study of 22 Asian cases according to WHO-EORTC classification.
Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, PR China.
- Am J Surg Pathol. 2008 Oct;32(10):1495-502. Abstract quote
Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is defined as a rare cytotoxic alpha/beta T-cell lymphoma characterized by primary involvement of subcutaneous tissue mimicking panniculitis and a predominant CD3+/CD4-/CD8+ phenotype in 2005 World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification for cutaneous lymphomas.
We presented a detailed study of SPTL, describing clinicopathologic, immunophenotypic, and molecular features of 22 cases in China. Strict diagnostic criteria according to the WHO-EORTC definition were applied to the diagnosis of all SPTL cases. Besides the common features described before, unusual CD4+/CD8- and CD4-/CD8- T-cell phenotypes were noted in 2 of our cases, respectively. CD30 was negative in all cases and CD56 was focally positive in 2 cases. Mortality in cases with angioinvasion (75%) was significantly higher than that in cases without angioinvasion (14.3%). Epstein-Barr virus (EBV) infection was detected in 1 immunocompetent patient by in situ hybridization. The frequency of rearranged TCRB, TCRG, and TCRD genes detected by BIOMED-2 multiplex polymerase chain reaction tubes was 80%, 67%, and 13%, respectively, with a total clonality detection rate of 100%. Clinical follow-up was available in 18 patients, ranging from 6 to 80 months. Most patients obtained complete or partial remission after therapy including one accompanied with EBV infection; 5 patients died: 3 of disease progression, 1 of severe infection, and 1 of complications caused by diabetes and hypertension.
We conclude that SPTL as a cytotoxic lymphoma derived from alpha/beta T cell has a predominant CD4-/CD8+ phenotype, but unusual CD4+/CD8- and CD4-/CD8- phenotypes do exist. Owing to its indolent clinical course and relatively high survival rate, SPTL should be differentiated from cutaneous gamma/delta T-cell lymphoma. EBV is generally absent in SPTL but can rarely be detected especially in Asian population. Angioinvasion is a poor prognostic factor in SPTL.
Subcutaneous, blastic natural killer (NK), NK/T-cell, and other cytotoxic lymphomas of the skin: a morphologic, immunophenotypic, and molecular study of 50 patients.
Massone C, Chott A, Metze D, Kerl K, Citarella L, Vale E, Kerl H, Cerroni L.
Department of Dermatology, University of Graz, Austria.
Am J Surg Pathol. 2004 Jun;28(6):719-35. Abstract quote
A new group of subcutaneous, natural killer (NK), NK/T-cell, and other cytotoxic T-cell lymphomas of the skin has been recently described, and some have been included as distinct clinicopathologic entities in the classification of hematologic malignancies recently proposed by the World Health Organization.
In the European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas, they would be classified either as CD30- large T-cell lymphoma, small/medium pleomorphic T-cell lymphoma, or subcutaneous T-cell lymphoma. Precise clinicopathologic and prognostic features of all of them have not yet been well characterized.
We studied retrospectively 81 biopsies from 50 patients with subcutaneous, blastic natural killer (NK), NK/T-cell, or other non-mycosis fungoides cytotoxic T-cell lymphomas of the skin. Clinical, morphologic, phenotypical, and genetic features and data on Epstein-Barr virus association allowed us to classify our cases according to the following 7 categories: a) subcutaneous "panniculitis-like" T-cell lymphoma (SPTCL): 10 cases (estimated 5-year survival: 80%); b) blastic NK-cell lymphoma: 12 cases (estimated 5-year survival: 0%); c) nasal-type extranodal NK/T-cell lymphoma: 5 patients (estimated 5-year survival: 0%); d) epidermotropic CD8+ T-cell lymphoma: 5 cases (estimated 5-year survival: 0%); e) cutaneous gamma/delta T-cell lymphoma: 8 cases (estimated 5-year survival: 0%); f) cutaneous alpha/beta pleomorphic T-cell lymphoma: 8 cases (estimated 5-year survival: 0%); and g) cutaneous medium/large pleomorphic T-cell lymphoma, not otherwise specified: 2 cases.
Our study shows that these cutaneous lymphomas can be classified according to precise diagnostic categories. With the exception of SPTCL, analysis of follow-up data from our patients showed that these groups of lymphomas are characterized by an aggressive course, regardless of the diagnostic category.
Clinicopathologic Analysis of 22 Cases of Subcutaneous Panniculitis-Like CD56– or CD56+ Lymphoma and Review of 44 Other Reported Cases
Morishige Takeshita, MD, etal.
Am J Clin Pathol 2004;121:408-416 Abstract quote
In 22 histologic cases of subcutaneous panniculitis-like lymphoma, we studied the clinicopathologic differences between CD56– and CD56+ cases (11 each). CD56– cases had skin ulcers (1 [9%]); tumor invasion in the superficial dermis (1 [9%]); erythrophagocytosis (10 [91%]); and medium-sized (11 [100%]), CD8+ (10 [91%]), T-cell receptor (TcR) b F1+ (10 [91%]), and CD95 (Fas)– tumor cells. CD56+ cases had skin ulcers (9 [82%]); tumor invasion in the superficial dermis (8 [73%]); erythrophagocytosis (1 [9%]); and pleomorphic large (10 [91%]), CD8+ (2/10 [20%]), TcR b F1+ (3/10 [30%]), and CD95 (Fas)+ (7/10 [70%]) tumor cells. These 7 factors were significantly different between groups ( P < .01).
Median survival rates were 96 and 12 months for the CD56– and CD56+ groups, respectively. Age younger than 40 years, no skin ulcers, no tumor invasion in the superficial dermis, and CD8+, TcR b F1+, CD95 (Fas)–, and CD56– tumor cells were significantly better prognostic factors ( P < .01). The CD56– and CD56+ groups showed different tumor cell characteristics, clinicopathologic findings, and prognosis. In the CD56+ group, 1 was g / d T-cell phenotype, 3 were a / b T-cell, and 6 were TcR b F1– and g / d – NK/T-cell, and 3 NK/T-cell cases had nuclear signals of Epstein-Barr virus–encoded RNA.
Cases of CD56+ T- and NK/T-cell lymphoma had similar clinicopathologic findings and prognosis.
Clinicopathologic differences between 22 cases of CD56-negative and CD56-positive subcutaneous panniculitis-like lymphoma in Japan.
Takeshita M, Okamura S, Oshiro Y, Okamoto S, Matsuki Y, Nakashima Y, Okamura T, Shiratsuchi M, Hayashi T, Kikuchi M.
Department of Pathology and Clinical Research Institute, National Kyushu Medical Center, Fukuoka, Japan.
Hum Pathol. 2004 Feb;35(2):231-9 Abstract quote.
CD56 is an important marker for prospecting clinicopathologic features of cytotoxic T-cell and natural killer (NK)/T-cell lymphomas.
We examined 22 cases of subcutaneous panniculitis-like lymphoma and classified these into CD56-positive and CD56-negative groups. The 11 CD56-negative cases were mainly in the younger age group and had systemic subcutaneous nodules without ulceration. They exhibited subcutaneous invasion by medium-sized lymphoma cells, scattered erythrophagocytosis, patchy necrosis, and little tumor invasion in the superficial dermis. Their lymphoma cells had characteristics of CD3 epsilon-, CD8-, TcR beta F1-, T-cell intracellular antigen (TIA)1-, and granenzyme B-positive cytotoxic T cells and were negative for apoptosis-promoting proteins CD95 (Fas), Bax, CPP32 (caspase 3), and p53 (DO7). Ten patients were alive despite clinical signs of hemophagocytic syndrome and relapses in 7 cases.
The 11 CD56-positive cases had systemic ulcerative skin tumors composed of pleomorphic lymphoma cells with massive necrosis and little erythrophagocytosis involving the subcutis and also often the whole dermis. Their tumor cells were positive for CD3 epsilon, TIA1, granenzyme B, CD95, CD95L (Fas ligand), Bax, and CPP32. Three cases were of the TcR beta F1-positive phenotype, 1 was of the TcR gamma/delta-positive T-cell phenotype, and 6 were of the TcR beta F1- and TcR gamma/delta-negative NK/T-cell phenotype. Six cases were p53 (DO7) positive. Seven cases had complications of liver dysfunction and cytopenia, and 8 died of disease. One CD56-negative case and 3 CD56-positive cases had nuclear signals of Epstein-Barr virus-encoded RNA in their lymphoma cells.
The 2 groups had significantly (P <0.01) different prognoses by Kaplan-Meier and log-rank methods. Patients with CD56-negative and CD56-positive groups had statistically different clinicopathologic, immunohistologic, and functional findings and prognoses.
SKIN Multiple inflammatory subcutaneous nodules lasting for several months to years
J Cutan Pathol. 2006 Jun;33(6):418-25 Abstract quote.
Background: Subcutaneous T-cell lymphoma (STCL) represents a controversial entity and a confused concept in the field of cutaneous T-cell lymphomas (CTCLs). Recently, alpha/beta(+)/CD8(+) STCL has been recognized by the new World Health Organization (WHO)-European Organization for Research and Treatment of Cancer (EORTC) classification of primary cutaneous lymphomas as a distinct entity in the group of CTCLs.
Observations: We reviewed a series of 53 biopsies from 26 patients (F : M = 19:7; median age: 48; range 18-87) of cutaneous B- and T-cell lymphomas characterized by prominent involvement of the subcutaneous tissue. We could classify our cases according to the following seven categories - (i) STCL: n = 16; (ii) extranodal NK/T-cell lymphoma, nasal type: n = 2; (iii) cutaneous gamma/delta T-cell lymphoma: n = 2; (iv) anaplastic CD30(+) large T-cell lymphoma: n = 1; (v) diffuse large B-cell lymphoma, secondary cutaneous: n = 3; (vi) lymphoplasmacytic lymphoma, secondary cutaneous: n = 1; (vii) specific cutaneous manifestations of myelogenous leukemia: n = 1.
Conclusions: We demonstrated the protean nature of lymphomas with prominent involvement of the subcutaneous fat tissues. The term STCL should be restricted to a homogeneous group of cases characterized morphologically by an exclusive involvement of subcutaneous tissues, immunohistochemically by a T-cytotoxic alpha/beta phenotype, and biologically by a relatively good prognosis.
Subcutaneous Panniculitis-Like T-Cell Lymphoma An Elusive Case Presenting As Lipomembranous Panniculitis and A Review of 72 Cases in the Literature
Roger H. Weenig, M.D., M.P.H.; Christine S. Ng, M.D.; Charles Perniciaro, M.D.
From the Department of Dermatology, Mayo Clinic, Jacksonville, Florida, and Rochester, Minnesota.
Am J Dermatopathol 2001;23:206-215 Abstract quote
We present a remarkable case of subcutaneous panniculitic T-cell lymphoma (SPTL) that eluded diagnosis for 14 years and illustrates the importance of continued follow-up with repeat biopsy when SPTL is suspected. This case is unusual in that multiple biopsies demonstrated either a nonspecific panniculitis or lipomembranous panniculitis with calcified lipomembranes.
A clinicopathologic review of 72 cases of SPTL from the English language literature is also presented, and approaches to diagnosis and treatment are reviewed.
HISTOLOGICAL TYPES CHARACTERIZATION Erythrophagocytosis Histiocytes and histiocyte-like cells are T cells which exhibit phagocytosis of red blood cells ATYPICAL LYMPHOCYTIC LOBULAR PANNICULITIS Atypical lymphocytic lobular panniculitis.
Magro CM, Neil Crowson A, Byrd JC, David Soleymani A, Shendrik I.
Department of Pathology, St. John Medical Center and Regional Medical Laboratories, Tulsa, OK, D. Warren Brown Professor of Leukemia Research, Department of Dermatology, The Ohio State University, Columbus, OH, and Creighton University, Omaha, NE, USA.
J Cutan Pathol. 2004 Apr;31(4):300-6. Abstract quote
BACKGROUND: Although subcutaneous T-cell lymphoma (SCTCL) is considered an aggressive form of lymphoma, some patients manifest a long waxing and waning phase unaccompanied by constitutional symptoms.
METHODS: Twelve patients were prospectively encountered, presenting with a lymphocytic panniculitis accompanied by lymphoid atypia, although not fulfilling criteria for SCTCL. Clinical, histologic, phenotypic, and genotypic analyses were conducted.
RESULTS: There were five men, one boy, and six women; none had symptoms compatible with lupus erythematosus or aggressive SCTCL. All but two had a waxing and waning course of years. Four patients had periodic cytopenias accompanied by fevers. While responding somewhat to prednisone, the lesions relapsed. In one patient, treatment with alemtuzumab (CAMPATH-1) led to complete lesional resolution with no recurrence. Light microscopy showed expansion of the interstices of the fat lobule by mildly atypical lymphocytes of the CD4 subset in 10 biopsies from eight patients; in the other four patients, there was an increase in CD8 lymphocytes. There was diminished expression of CD5 and/or CD7 in the majority of biopsies. Ten of 13 biopsies showed clonal T-cell receptor-gamma rearrangements.
CONCLUSIONS: We apply the term atypical lymphocytic lobular panniculitis to this distinctive form of lymphocytic panniculitis manifesting this light microscopic, phenotypic, and genotypic profile.
CHARACTERIZATION T cells CD2 and 3+
Loss of CD5 and/or CD7
Occasional cases with CD8 phenotype and CD56
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES LUPUS ERYTHEMATOSUS
- Fatal subcutaneous panniculitis-like T-cell lymphoma with interface change and dermal mucin, a dead ringer for lupus erythematosus.
Ma L, Bandarchi B, Glusac EJ.
Department of Pathology, Yale New Haven Hospital, Yale University, School of Medicine, New Haven, CT, USA.
J Cutan Pathol. 2005 May;32(5):360-5. Abstract quote
We report a 48-year-old man who presented with ulcerated plaques and nodules of the lower extremities. Skin biopsies revealed a dense lymphocytic infiltrate involving the dermis and the subcutis in a lobular and septal pattern. No overt cytological atypia was present. Notably, several features resembling lupus erythematosus were present, including vacuolar interface change and abundant dermal mucin deposition.
The patient developed pulmonary nodules, and a lung biopsy showed a perivascular and interstitial lymphoid infiltrate without overt atypia. The cutaneous and pulmonary lymphoid infiltrates showed similar immunohistochemical profiles: CD3(+) CD4(-) CD8(+/-) CD56(+). Monoclonal rearrangements of the T-cell receptor gamma gene with similar migration patterns were identified from both locations. The patient developed fatal hemophagocytic syndrome, involving liver, spleen, lymph nodes, and bone marrow.
This case is one amongst the rare reports of subcutaneous panniculitis-like T-cell lymphoma with systemic involvement.
Lupus profundus, indeterminate lymphocytic lobular panniculitis and subcutaneous T-cell lymphoma: a spectrum of subcuticular T-cell lymphoid dyscrasia.
Magro CM, Crowson AN, Kovatich AJ, Burns F.
Ohio State University Medical Center, Columbus, Ohio, USA.
J Cutan Pathol 2001 May;28(5):235-47 Abstract quote
INTRODUCTION: The diagnosis and classification of lymphocytic lobular panniculitis (LLP) has historically proven to be a difficult challenge. We encountered 32 cases of primary LLP which could be categorized as: 1) lupus erythematosus profundus (LEP) (19 patients); 2) an indeterminate group termed indeterminate lymphocytic lobular panniculitis (ILLP) (6 patients); and 3) subcutaneous T-cell lymphoma (SCTCL) (7 patients).
OBJECTIVE: We attempted to better define the subtypes of LLP by morphologic, phenotypic and genotypic features and to correlate those features to clinical presentation and outcome.
METHOD: Skin biopsy material was studied by conventional light microscopy, through immunophenotyping performed on sections from paraffin-embedded, formalin-fixed tissue and in some cases on sections of tissue frozen after receipt in physiological (Michel's) medium, and by polymerase chain reaction single-stranded conformational polymorphism analysis to assess for clonality of T-lymphocytes. Clinical features were correlated to histologic, phenotypic, and genotypic analyses.
RESULTS: Patients with LEP had a prior diagnosis of LE or overlying skin changes which light microscopically were characteristic of LE. Patients with ILLP had no concurrent or prior history of LE, no systemic symptoms or cytopenias, and a clinical course not suggestive of lymphoma. Cases of SCTCL showed hemophagocytic syndrome and/or lesional progression with demise attributable to the disease. Lesions in all groups showed proximal extremity predilection. Females predominated in the LEP group. The average age of onset was 38, 40 and 55 years in the LEP, ILLP and SCTCL groups, respectively. Cytopenia was seen in 4 LEP patients; 1 also developed fever. In LEP and ILLP, lesions resolved with hydroxychloroquine and/or steroid therapy, with recurrences following cessation of therapy. In the SCTCL group 4 developed hemophagocytic syndrome, 4 died within 2 years of diagnosis, and 3 went into remission following chemotherapy. The LEP and SCTCL groups manifested histological similarities: dense perieccrine and lobular lymphocytic infiltration, lymphoid atypia, histiocytes with ingested debris, eosinophilic necrosis of the fat lobule and thrombosis. The atypical lymphocytes although pleomorphic did not have a cerebriform morphology. The infiltrate in ILLP had a similar cytomorphology and distribution with variable angioinvasion which in all save one case was of lesser intensity and was not associated with significant fat necrosis or vasculitis. Germinal centers, dermal/subcuticular mucin deposition and an atrophying interface dermatitis with hyperkeratosis and follicular plugging were largely confined to the LEP group. Erythrophagocytosis, characteristic of SCTCL, usually indicated a supervening subcuticular lymphoid dyscrasia when encountered in ILLP and LEP. SCTCL showed a selective loss of CD5 expression with or without diminution in CD7 and monoclonal CD3 expression. Of 4 cases studied, 3 showed a CD8 dominant infiltrate while 2 others exhibited CD56 and CD30 positivity, respectively. All cases of SCTCL with amplifiable DNA showed T-cell clonality. Similar molecular and phenotypic features indicative of subcuticular lymphoid dyscrasia were encountered in cases of LEP and ILLP including a reduction in CD5, CD7, and/or monoclonal CD3 expression, a preponderance of CD8 lymphocytes within the subcutaneous fat and T-cell clonality. These cases showed lymphoid atypia with variable erythrophagocytosis. Cases of phenotypically abnormal and/or clonal LEP showed one or more of local destruction, lesional size progression, fever, and cytopenias, but lesions responded to hydroxychloroquine and/or prednisone therapy and death attributable to panniculitis could not be documented. Cases that were phenotypically normal and without clonality had none of the aforesaid atypical clinical features.
CONCLUSION: Lymphoid atypia, erythrophagocytosis, loss of certain pan T-cell markers, a reduced CD4/8 ratio and TCR rearrangement define subcuticular T-cell lymphoid dyscrasia, including a subset of LEP and ILLP. The subcuticular lymphoid infiltrates represent a spectrum of histologic, immunophenotypic, and molecular abnormalities which range from those which are clearly benign to those which are clearly neoplastic, and also encompasses those cases which defy precise classification into the two aforesaid poles.
- Rimming of Adipocytes By Neoplastic Lymphocytes: A Histopathologic Feature Not Restricted to Subcutaneous T-Cell Lymphoma.
Lozzi GP, Massone C, Citarella L, Kerl H, Cerroni L.
From the *Department of Dermatology, Medical University of Graz, Austria; daggerDepartment of Dermatology, University of L'Aquila, Italy; and double daggerDepartment of Dermatology, University of Rome "Tor Vergata," Italy.
Am J Dermatopathol. 2006 Feb;28(1):9-12. Abstract quote
Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma of the skin presenting with histopathologic features simulating those of a lobular panniculitis.
The presence of neoplastic T-lymphocytes forming a rim around the individual fat cells in the subcutaneous lobules, so-called "rimming" of adipocytes, is considered a characteristic morphologic feature of this type of cutaneous lymphoma.
In this study we reviewed a series of 45 biopsy specimens of primary and secondary cutaneous B- and T-cell lymphomas and one of myeloid leukemia involving the subcutaneous tissues and showing rimming of adipocytes (subcutaneous panniculitis-like T-cell lymphoma: n = 16; mycosis fungoides, tumor stage: n = 3; aggressive epidermotropic CD8 T-cell lymphoma: n = 2; cutaneous gamma/delta T-cell lymphoma: n = 4; extranodal NK/T-cell lymphoma, nasal type: n = 4; cutaneous medium-large pleomorphic T-cell lymphoma, NOS: n = 5; CD4/CD56 hematodermic neoplasm (blastic NK-cell lymphoma): n = 7; secondary cutaneous large B-cell lymphoma: n = 3; secondary cutaneous lymphoplasmacytic lymphoma: n = 1; specific cutaneous manifestations of acute myelogenous leukemia: n = 1).
We could demonstrate that rimming of adipocytes by neoplastic cells can be recognized not only in subcutaneous panniculitis-like T-cell lymphoma, but also in several different entities of malignant lymphoma with skin involvement. Precise classification of cases with prominent involvement of the subcutaneous tissues can only be achieved upon precise correlation of clinicopathologic and phenotypic features.
Rimming of adipocytes should not be considered specific of subcutaneous panniculitis-like T-cell lymphoma.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSIS
Subcutaneous panniculitis-like T-cell lymphoma: a clinicopathological, immunophenotypic and molecular analysis of six patients.
Hoque SR, Child FJ, Whittaker SJ, Ferreira S, Orchard G, Jenner K, Spittle M, Russell-Jones R.
Department of Dermatopathology, St John's Institute of Dermatology, St Thomas' Hospital, London, UK.
Br J Dermatol. 2003 Mar;148(3):516-25. Abstract quote
BACKGROUND: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma of the skin. In the World Health Organization classification of T-cell and natural killer cell lymphoma it is listed as an example of extranodal lymphoma. In practice, however, it is most likely to present to a dermatologist.
OBJECTIVES: To describe the clinicopathological, immunophenotypic and molecular features of six U.K. patients with SPTCL.
METHODS: The clinical, histological and immunophenotypic features were reviewed. T-cell receptor (TCR) gene analysis was performed on blood and tissue samples using polymerase chain reaction/single-strand conformational polymorphism analysis of the TCR-gamma gene using consensus primers. In situ hybridization was performed on lesional skin to detect mRNA for Epstein-Barr virus (EBV).
RESULTS: All patients presented with subcutaneous nodules, plaques or ulceration, and three had systemic symptoms. All biopsies exhibited an infiltrate of medium to large pleomorphic cells involving the subcutis with characteristic rimming of fat spaces. Five showed areas of necrosis, but only one showed marked cytophagia. In three cases the neoplastic cells did not express TCR-beta. One was strongly p53 positive, and the other two were CD56 positive. Both these patients showed epidermal involvement with lichenoid changes histologically, and both developed the haemophagocytic syndrome. The other three cases were TCR-beta positive, CD8 positive and CD56 negative. All cases were positive with pan T-cell markers and also for the cytotoxic granule protein T-cell intracellular antigen-1 and granzyme B. All cases were EBV negative both by immunostaining (latent membrane protein-1) and by in situ hybridization (EBV-encoded mRNA). TCR gene analysis revealed a T-cell clone in four of five cases; two of these patients had an identical T-cell clone in the peripheral blood. The median survival was 16 months. However, two of the three TCR-beta-negative patients have died, whereas none of the TCR-beta-positive patients has died.
CONCLUSIONS: This is the first series of SPTCL patients to be reported in the U.K. and the data support the view that there are two subsets of SPTCL: those derived from gammadelta T cells which carry a poor prognosis, and are usually CD56 positive, and a more indolent group derived from alphabeta T cells.
Successful treatment of a patient with subcutaneous panniculitis-like T-cell lymphoma with high-dose chemotherapy and total body irradiation.
Mukai HY, Okoshi Y, Shimizu S, Katsura Y, Takei N, Hasegawa Y, Kojima H, Mori N, Nagasawa T.
Division of Hematology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. .
Eur J Haematol. 2003 Jun;70(6):413-6. Abstract quote
A 24-yr-old man was referred for fever, right cheek swelling, subcutaneous tumor and liver dysfunction. Physical examination showed an elastic hard subcutaneous tumor on the right cheek, left axillary lymph node swelling and multiple small subcutaneous tumors in the trunk.
Laboratory examinations showed elevated levels of transaminase, soluble interleukin-2 receptor and ferritin. Biopsy of the subcutaneous tumor showed proliferation of medium-sized cells with abundant clear cytoplasm and hyperchromatic nuclei among the subcutaneous fat tissues. These cells showed CD3+, CD4-, CD8+, CD56- and CD20- phenotype and possessed cytotoxic molecules such as granzyme B and T-cell intracellular antigen-1.
Bone marrow aspiration showed proliferation of small numbers of abnormal lymphocytes with severe hemophagocytosis. He was thus diagnosed as having subcutaneous panniculitis-like T-cell lymphoma (SPTCL) and treated with dose-escalated CHOP regimen. After three courses of the chemotherapy, he was further treated with high-dose chemotherapy and total body irradiation (TBI) with autologous peripheral blood stem cell rescue. Thereafter, he has been in remission for more than 2 yr.
We consider that SPTCL with hemophagocytosis is an extremely aggressive disease, and high-dose chemotherapy and TBI should be included for the choice of the treatment.
Denileukin diftitox for the treatment of panniculitic lymphoma.
McGinnis KS, Shapiro M, Junkins-Hopkins JM, Smith M, Lessin SR, Vittorio CC, Rook AH.
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