0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Observation |

Cytophagic Histiocytic Panniculitis and Subcutaneous Panniculitis-like T-Cell Lymphoma:  Report of 7 Cases FREE

Angelo V. Marzano, MD; Emilio Berti, MD; Marco Paulli, MD; Ruggero Caputo, MD
[+] Author Affiliations

From the Institute of Dermatological Sciences, University of Milan, and IRCCS Ospedale Maggiore, Milan (Drs Marzano, Berti, and Caputo) and Anatomic Pathology, IRCCS Policlinico S. Matteo and University of Pavia, Pavia (Dr Paulli), Italy.


Arch Dermatol. 2000;136(7):889-896. doi:10.1001/archderm.136.7.889.
Text Size: A A A
Published online

ABSTRACT

Background  Cytophagic histiocytic panniculitis (CHP) is a rare subtype of panniculitis that usually follows a fatal course, with a terminal hemophagocytic syndrome. Recent reports on a subset of peripheral T-cell lymphoma named subcutaneous panniculitis-like T-cell lymphoma (SPTL) raised the question about the relationship between these entities.

Observations  We describe 7 patients in the study: 1with fatal CHP, 4 with SPTL, and 2 with long-term CHP. The 5 patients with fatal CHP and SPTL died of complications of hemophagocytic syndrome, with a disease duration ranging from 8 to 74 months. The other 2 patients were still alive 6 and 41 years after disease onset. Immunohistochemical results proved that 2 of the SPTL cases were type α/β and expressed the cytotoxic/suppressor antigen CD8, while the other 2 were type γ/δ and were positive for the natural killer–associated antigen CD56. In these 4 cases, molecular biology studies by polymerase chain reaction detected T-cell receptor γ gene rearrangement, indicating a clonal process. In contrast, in the 2 patients who had long-term CHP, the polymerase chain reaction results failed to disclose clonality. In the subject with fatal CHP, genotypic analysis was not performed.

Conclusion  Our observations suggest that CHP and SPTL may span a clinicopathologic spectrum in which there is a natural disease progression from CHP to SPTL.

Figures in this Article

IN 1980, Winkelmann and Bowie1 described a subtype of panniculitis named histiocytic cytophagic panniculitis (CHP) that was histologically characterized by a mixed lobular and segmental panniculitis with a proliferation of benign-appearing cytophagic histiocytes. The disease was associated with a fatal hemophagocytic syndrome. The hemophagocytic syndrome seen in CHP may also be associated with many other diseases, most notably so-called subcutaneous panniculitis-like T-cell lymphoma (SPTL),220 raising the question about the relationship between CHP and SPTL. This report describes the clinical presentation and course, and the pathologic, immunohistochemical, and molecular genetic findings of 7 patients, 5 of whom had fatal CHP or SPTL, while the other 2 had a long-term form of CHP. We suggest that CHP and SPTL exist in a continuum and that the former may precede the latter.

PATIENTS, MATERIALS, AND METHODS

PATIENTS

The study included 7 patients with CHP or SPTL registered in the files of the Institute of Dermatological Sciences of the University of Milan and IRCCS, Milan, Italy. Staging procedures included routine blood cell counts and chemistry analyses, cervicothoraco-abdominal computed tomography, and bone marrow biopsy and aspirates. Autopsy was performed in one of these cases (patient 1). Clinical parameters evaluated were age, sex, type of skin lesions at presentation, systemic symptoms and signs, duration of disease, treatment, outcome, and follow-up.

HISTOPATHOLOGY

Skin biopsy specimens obtained from each patient both at onset and whenever possible during the progression of the disease were all reviewed. The skin specimens were fixed in 10% buffered formalin, embedded in paraffin, and sectioned into 3-µm sections that were stained with hematoxylin-eosin.

IMMUNOHISTOCHEMISTRY

Immunohistochemical stains were performed in all cases on paraffin-embedded skin sections and on frozen material by using the panel of antibodies indicated in Table 1. A standard alkaline phosphatase anti–alkaline phosphatase technique (Dakopatts, Glostrup, Denmark) was carried out according to a previously described method.21

Table Graphic Jump LocationTable 1. Antibody Reagents Used for Immunohistochemical Studies for CHP and SPTL*
MOLECULAR BIOLOGY

T-cell receptor (TCR) gene rearrangement was evaluated in 6 of the 7 cases by a polymerase chain reaction assay coupled with nondenaturing polyacrylamide gel electrophoresis (PAGE) according to a method previously described.22 The amplification of the TCRγ chain locus V-J junctional region was performed by using the oligonucleotide-specific primers for J coupled with V2a, V9, and V10. Fifteen microliters of the amplified material then was run overnight on 12% nondenaturing PAGE in Tris, boric acid, EDTA (TBE) buffer at 70 V. Finally, heteroduplex patterns were revealed by ethidium bromide staining. The presence of a nongermline band, compared with previously identified positive and negative controls, was indicative of rearrangement of the TCRγ chain.

EPSTEIN-BARR VIRUS EBER1 IN SITU HYBRIDIZATION

In all 7 cases, in situ hybridization studies for the detection of Epstein-Barr virus (EBV) RNA were performed using a 30–base pair oligonucleotide probe complementary to a portion of the EBER1 gene, a region of the EBV genome that is actively transcribed (up to 107 copies per cell) in latently infected cells.23 The methods for these studies have been reported previously.23

RESULTS

CLINICAL FEATURES

The clinical findings in these 7 patients are summarized in Table 2 and Table 3 (see also Figure 1). The patients included 5 females and 2 males with a median age of 37 years (range, 10-56 years). The duration of disease ranged from 6 months to 38 years. The range of follow-up was 2 months to 3 years. Four patients (patients 4-7) diagnosed as having SPTL died of the disease 8 to 74 months following its onset. Patient 1 was diagnosed as having CHP and experienced a rapidly progressive clinical course (8 months). In contrast, the other 2 patients with CHP were still alive 6 and 41 years after the onset of the disease.

Table Graphic Jump LocationTable 2. Clinical Summary of 7 Cases of CHP and SPTL*
Table Graphic Jump LocationTable 3. Systemic Symptoms, Major Laboratory and Histopathologic Findings, and Molecular Biology Aspects of 7 Cases of CHP and SPTL*
Place holder to copy figure label and caption
Figure 1.

A, Large, erythematous, violaceous, ulcerated plaque on the thigh in case 1. B, The unique clinical picture in case 3. C, Dramatic cutaneous features of subcutaneous panniculitis-like T-cell lymphoma (SPTL) in case 4. D, Slightly erythematous subcutaneous nodules on the patient's back as initial clinical presentation of SPTL in case 5.

Graphic Jump Location
HISTOPATHOLOGIC FINDINGS

In 4 patients (patients 4-7), histopathologic findings of skin biopsy specimens disclosed a dense and diffuse infiltrate of atypical small to medium lymphocytes in the dermis and subcutis consistent with peripheral T-cell lymphoma involving subcutaneous tissue (Figure 2, A and B, and Table 3). Hemophagocytosis, particularly leukophagocytosis, was evident. In the other 3 cases, histologic findings suggested CHP (Figure 2, C). Histopathologic features of other organ sites are also summarized in Table 3 (Figure 2, D).

Place holder to copy figure label and caption
Figure 2.

A, Histopathologic findings from biopsy skin specimen of case 6 showing a cellular infiltrate entirely involving the subcutaneous tissue (hematoxylin-eosin, original magnification ×12.5). B, Case 7: Dense infiltrate mainly composed of small to medium atypical lymphocytes, sometimes showing an angiocentric distribution and forming rings around the adipose tissue lobules (hematoxylin-eosin, original magnification ×400). C, Case 2: Inflammatory lymphohistiocytic infiltrate in the subcutis with tissue necrosis and karyorrhexis. Several cytophagic histiocytes are visible (hematoxylin-eosin, original magnification ×400). D, Case 1: Bone marrow biopsy specimen with prominent erythrophagia indicated by large histiocytes of multiple erythrocytes (hematoxylin-eosin, original magnification ×400).

Graphic Jump Location
IMMUNOHISTOCHEMISTRY

Results from immunohistochemical studies are in Table 4. In all 4 cases (patients 4-7) in which the histopathologic findings were suggestive of lymphoma, the atypical lymphocytes showed a CD2+, CD3+, and CD45RO+ T-cell phenotype with clear evidence of T-cell antigen loss (CD5 and/or CD7). All cases expressed TCRs: 2 cases (patients 6 and 7) proved to be α/β (βF1+) SPTL positive for the cytotoxic/suppressor CD8 antigen (Figure 3, A), while the other 2 (patients 4 and 5) were γ/δ (TCRδ-1+) SPTL expressing the natural killer (NK)–associated antigen CD56. Interestingly, in all the above cases, most of the neoplastic lymphocytes were strongly labeled with monoclonal antibodies directed against T-cell restricted intracellular antigen 1 (TIA-1), a cytotoxic cell marker that often forms a ring around fat vacuoles in the subcutaneous tissue (Figure 3, B). In addition, in case 4, we found intense staining for CD68 (KP1) in abundant histiocytes, some of which were large and cytophagic (Figure 3, C).

Table Graphic Jump LocationTable 4. Immunohistochemical Studies of 7 Cases of CHP and SPTL*
Place holder to copy figure label and caption
Figure 3.

Immunohistochemical studies showing reactivity for CD8 (A), T-cell restricted intracellular antigen 1 (TIA-1) (B), and CD68 (C) (original magnification ×400).

Graphic Jump Location

In case 1, a strong expression of CD68 by the benign histiocytes, several of which were cytophagic, admixed with numerous CD3+ and CD8+ T lymphocytes, which were moderately positive for TIA-1, in the subcutaneous infiltrate was demonstrated.

In case 2, in addition to CD68+ histiocytes, numerous CD4+ and CD8+ T lymphocytes slightly expressing TIA-1 were seen.

In case 3, the cellular infiltrate in the subcutis was mainly composed of CD68+ histiocytes with several CD4+ and scattered CD8+ T lymphocytes negative for TIA-1.

MOLECULAR BIOLOGY

Results from genotypic analysis are shown in Table 3 and Figure 4.

Place holder to copy figure label and caption
Figure 4.

Polyacrylamide gel electrophoresis of polymerase chain reaction products showing the T-cell receptor (TCR) γ chain gene rearrangement in 3 cases (lanes 3, 5, and 6, which correspond to cases 4, 5, and 6, respectively, in the present study) of subcutaneous panniculitis-like T-cell lymphoma. The other patients, which are not included in this study (lanes 1, 2, 4, and 7), have polyclonal TCRγ genes. M indicates DNA molecular weight marker; C−, negative control; C+, positive control; and bp, base pairs.

Graphic Jump Location
EBV EBER1 IN SITU HYBRIDIZATION

In all 7 cases, results did not show any positive hybridization signals to EBER1 in the skin biopsy tissue sections.

COMMENT

In their report on CHP, Crotty and Winkelmann24 described 5 patients with multiple inflammatory subcutaneous nodules who experienced a terminal hemorrhagic diathesis after a clinical course of 6 months to 10 years. Clinical manifestations of systemic involvement consisted of fever, hepatosplenomegaly, mucosal ulcers, and serosal effusions. Pancytopenia, liver failure, and intravascular coagulation were present in all their patients. The histologic picture was characterized by a mixed lobular and segmental histiocytic cytophagic panniculitis. Erythrophagocytosis and cytophagocytosis by benign-appearing histiocytes were observed in internal organs, particularly the lymph nodes, spleen, liver, and bone marrow.

Single reports of patients with CHP who have not experienced a fatal outcome 5, 16, and 28 years after the onset of the disease have been subsequently published.25,26 This nonfatal form of CHP differed in that systemic signs and symptoms were lacking, and cytophagia was not evident in extracutaneous organs.

With the widespread use of immunocytochemistry to characterize cellular infiltrates, the existence of malignant T-cell proliferations mimicking inflammatory panniculitis has been recognized.220

Gonzales et al2 first described T-cell lymphoma involving subcutaneous tissue as a rare, distinct subset of peripheral T-cell lymphoma (PTL) characterized by a propensity to be associated with a hemophagocytic syndrome and by an aggressive clinical course. This entity was categorized as a subtype of PTL by the International Lymphoma Study Group in 1994 under the term subcutaneous panniculitis-like T-cell lymphoma (SPTL).27

Thus, both the precise nature of SPTL and the overall complex relationship between CHP and SPTL remain to be clarified.

Peters and Winkelmann28 suggested that CHP might be a preneoplastic syndrome or a reactive process to a neoplastic disease. In fact, it is well known that erythrophagocytic syndromes occur uncommonly in a multitude of disorders, including infectious and neoplastic conditions.16

According to Wang et al,13 CHP is probably a low-grade T-cell lymphoma ab initio that with time might progress to the more aggressive SPTL.

We reported the clinical presentation, course, laboratory, histopathologic, immunocytochemical, and molecular genetic findings of 7 patients (5 female and 2 male) with CHP or SPTL to further characterize these entities.

Five patients (patients 1 and 4-7) died of complications of hemophagocytosis between 8 and 74 months following the onset of the disease. Four of these cases were characterized by the occurrence of panniculitis-like subcutaneous nodules initially difficult to classify as lymphoma with benign-appearing skin biopsy specimens. Subsequent biopsy specimens revealed progression to frank subcutaneous lymphoma, and clonality was documented by TCRγ gene rearrangement studies. In the other case (patient 1), immunohistological results were interpreted as classic CHP without proven lymphoma, but genotypic analysis could not be performed because adequate biopsy material was not available.

Cytophagia, particularly erythrophagia, was observed in bone marrow specimens of the patients cited above, but no bone marrow involvement by lymphoma was demonstrated in any of these cases. These findings are in agreement with the literature, extracutaneous involvement by SPTL having only rarely been described.9,16 In addition, autopsy studies2,16,29 of patients who died of CHP or SPTL have rarely been published. Autopsy examination performed in case 1 of our series revealed the presence of hemophagocytic histiocytosis without evidence of lymphoma in multiple organ sites, as previously reported.29 In the 4 cases in which histopathologic findings were consistent with subcutaneous lymphoma, immunohistochemical studies showed a CD2+, CD3+, and CD45RO+ T-cell phenotype of the neoplastic lymphocytes, with evidence of T-cell antigen loss (CD5 and/or CD7). Two of these cases (patients 6 and 7) proved to be α/β T-cell lymphomas expressing the T-suppressor/cytotoxic cell antigen CD8, which is usually related to aggressive clinical behavior.30,31 The other 2 cases (patients 4 and 5) were γ/δ T-cell lymphomas and expressed the antigen CD56. The CD56 antigen marks the cutaneous NK and NK-like T-cell lymphomas, recently described as a rare subset of aggressive cutaneous lymphomas.32 Interestingly, in all cases the atypical lymphocytes were strongly labeled with the monoclonal antibody directed against TIA-1/GMP-17 (a granule membrane protein of the cytotoxic lymphocytes).33 Expression of this monoclonal antibody has recently been described in several lymphomas regarded as being derived from lymphocytes with cytotoxic potential and thus characterized by aggressive clinical behavior.34 In this regard, this immunohistochemical finding and the others mentioned above could help explain the rapidly fatal course of SPTL. In the other 2 cases (patients 2 and 3), characterized by histopathologic aspects of CHP and absence of clonality, the patients experienced a chronic course and were still alive 6 and 41 years after the disease onset, respectively. These patients lacked all of the clinical features typical of the fatal form of CHP and also presented without pancytopenia. However, such a long duration does not permit the certain conclusion that this is a nonfatal disease, since anaplastic transformation could occur with time, as previously described.24,35 This possibility may also be supported by the observation that both these cases and 2 of those classified as SPTL (patients 6 and 7) initially presented with a spectrum of systemic symptoms, including fever, polyarthritis, and pericarditis, that mimicked an autoimmune disorder. Thus, a lupus-like clinical presentation seems to represent an initial disease stage marking an immunological dysfunction that could be one of the factors promoting the progression to lymphoma.

Perniciaro et al8 suggested that 2 distinct clinical presentations of SPTL exist. The first is characterized by a protracted CHP-like phase and the other type by a rapidly progressive clinical course. Various factors, most notably genetic or viral, may be involved in triggering the progression from panniculitis to malignant lymphoma. Emphasis has been placed on gene rearrangement studies to establish malignancy and to differentiate between CHP and SPTL, but this should not be done. In fact, clonal T-cell proliferations are seen in a multitude of benign conditions and are not predictive of outcome.36

Latent EBV infection has been detected in SPTL12,35,37 but neither in nonfatal35 nor in fatal37 CHP by EBV RNA (EBER1) in situ hybridization studies. Other investigators have also reported negative results for EBV at multiple organ sites from a patient with fatal CHP.38 In this regard, Craig et al37 recently suggested that CHP and SPTL may not be identical.

We also performed EBV RNA (EBER1) in situ hybridization on skin biopsy specimens from all patients in this series and obtained negative results both for CHP and for SPTL.

In summary, our observations suggest that it does not seem appropriate to differentiate SPTL and CHP and that, on the contrary, there is a natural disease progression from CHP to SPTL.

ARTICLE INFORMATION

Accepted for publication December 20, 1999.

Corresponding author: Angelo V. Marzano, MD, Istituto di Scienze Dermatologiche, University of Milan and IRCCS Ospedale Maggiore, Via Pace, 9, 20122 Milan, Italy.

REFERENCES

Winkelmann  RKBowie  EJ Hemorrhagic diathesis associated with benign histiocytic, cytophagic panniculitis and systemic histiocytosis. Arch Intern Med. 1980;1401460- 1463
Link to Article
Gonzales  CLMedeiros  JBraziel  RMJaffe  ES T-cell lymphoma involving subcutaneous tissue: a clinicopathologic entity commonly associated with hemophagocytic syndrome. Am J Surg Pathol. 1991;1517- 27
Link to Article
Tanaka  KHagari  YSano  YShimano  SNamba  K A case of T-cell lymphoma associated with panniculitis, progressive pancytopenia and hyperbilirubinemia. Br J Dermatol. 1990;123649- 652
Link to Article
Ashworth  JCoady  ATGuy  RBreathnach  SM Brawny cutaneous induration and granulomatous panniculitis in large cell non-Hodgkin's (T suppressor/cytotoxic cell) lymphoma. Br J Dermatol. 1989;120563- 569
Link to Article
Burg  GDummer  RWilhelm  M  et al.  A subcutaneous delta-positive T-cell lymphoma that produces interferon gamma. N Engl J Med. 1991;3251078- 1081
Link to Article
Liddle  BJKondratowicz  GMarsden  JR Panniculitis and lymphoma. Clin Exp Dermatol. 1991;1674- 75
Link to Article
Prescott  RJBanerjee  SSCross  PA Subcutaneous T-cell lymphoma with florid granulomatous panniculitis. Histopathology. 1992;20535- 537
Link to Article
Perniciaro  CZalla  MJWhite Jr  JWMenke  DM Subcutaneous T-cell lymphoma: report of two additional cases and further observations. Arch Dermatol. 1993;1291171- 1176
Link to Article
Mehregan  DASu  WPKurtin  PJ Subcutaneous T-cell lymphoma: a clinical, histopathologic and immunohistochemical study of six cases. J Cutan Pathol. 1994;21110- 117
Link to Article
Avinoach  IHalevy  SArgov  SSacks  M Gamma/delta T-cell lymphoma involving the subcutaneous tissue and associated with a hemophagocytic syndrome. Am J Dermatopathol. 1994;16426- 433
Link to Article
Monterroso  VBujan  WJaramillo  OMedeiros  LJ Subcutaneous tissue involvement by T-cell lymphoma: a report of 2 cases. Arch Dermatol. 1996;1321345- 1350
Link to Article
Cho  KHOh  JKKim  CWHeo  DSKim  ST Peripheral T-cell lymphoma involving subcutaneous tissue. Br J Dermatol. 1995;132290- 295
Link to Article
Wang  CYSu  WPKurtin  PJ Subcutaneous panniculitic T-cell lymphoma. Int J Dermatol. 1996;351- 8
Link to Article
Chan  YFLee  KCLlewellyn  H Subcutaneous T-cell lymphoma presenting as panniculitis in children: report of two cases. Pediatr Pathol. 1994;14595- 608
Link to Article
Romero  LSGoltz  RWNagi  CShin  SSHo  A Subcutaneous T-cell lymphoma with associated hemophagocytic syndrome and terminal leukemic transformation. J Am Acad Dermatol. 1996;34904- 910
Link to Article
Sajben  FPSchmidt  C Subcutaneous T-cell lymphoma: a case report and additional observations. Cutis. 1996;58297- 302
Von den Driesch  PStaib  GSimon  MSterry  W Subcutaneous T-cell lymphoma. J Am Acad Dermatol. 1997;36285- 289
Link to Article
Dargent  JLRoufosse  CDelville  JP  et al.  Subcutaneous panniculitis-like T-cell lymphoma: further evidence for a distinct neoplasm originating from large granular lymphocytes of T/NK phenotype. J Cutan Pathol. 1998;25394- 400
Link to Article
Salhany  KEMacon  WRChoi  JK  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;22881- 893
Link to Article
Kumar  SKrenacs  LMedeiros  J  et al.  Subcutaneous panniculitic T-cell lymphoma is a tumor of cytotoxic T lymphocytes. Hum Pathol. 1998;29397- 403
Link to Article
Cordell  JLFalini  BErber  WN  et al.  Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem. 1984;32219- 229
Link to Article
Bottaro  MBerti  EBiondi  AMigone  NCrosti  L Heteroduplex analysis of T-cell receptor gamma gene rearrangements for diagnosis and monitoring of cutaneous T-cell lymphomas. Blood. 1994;833271- 3278
Vasef  MAWeiss  LMChen  YYMedeiros  LJ Gastric lymphoepithelioma-like carcinoma and jejunal B-cell MALT lymphoma with large cell transformation: demonstration of EBV with identical gene deletions in the carcinoma and large cell lymphoma. Am J Clin Pathol. 1996;105560- 566
Crotty  CPWinkelmann  RK Cytophagic histiocytic panniculitis with fever, cytopenia, liver failure and terminal hemorrhagic diathesis. J Am Acad Dermatol. 1981;4181- 194
Link to Article
Barron  DRDavis  BRPomeranz  JRHines  JDPark  CH Cytophagic histiocytic panniculitis: a variant of malignant histiocytosis. Cancer. 1985;552538- 2542
Link to Article
White Jr  JWWinkelmann  RK Cytophagic histiocytic panniculitis is not always fatal. J Cutan Pathol. 1989;16137- 144
Link to Article
Harris  NLJaffe  ESStein  H  et al.  A revised European-American classification of lymphoid neoplasm: a proposal from the International Lymphoma Study Group. Blood. 1994;841361- 1392
Peters  MSWinkelmann  RK Cytophagic panniculitis and B-cell lymphoma. J Am Acad Dermatol. 1985;13882- 885
Link to Article
Perniciaro  CWinkelmann  RKEhrhardt  DR Fatal systemic histiocytic panniculitis: a histopathologic and immunohistochemical study of multiple organ sites. J Am Acad Dermatol. 1994;31901- 905
Link to Article
Urrutia  SPiris  MAOrradre  JLMartinez  BCruz  MAGarcia-Almagro  D Cytotoxic/suppressor (CD8+, CD4+) cutaneous T-cell lymphoma with aggressive course. Am J Dermatopathol. 1990;12603- 606
Link to Article
Berti  ETomasini  DVermeer  MHMeijer  CJAlessi  EWillemze  R Primary cutaneous CD8-positive epidermotropic cytotoxic T cell lymphomas: a distinct clinicopathologic entity with an aggressive clinical behavior. Am J Pathol. 1999;155483- 492
Link to Article
Natkunam  YSmoller  BRZehnder  JLDorfman  RFWarnke  RA Aggressive cutaneous NK and NK-like T-cell lymphomas: clinicopathologic, immunohistochemical, and molecular analysis of 12 cases. Am J Surg Pathol. 1999;23571- 581
Link to Article
Medley  QGKedersha  NO'Brien  S  et al.  Characterization of GMP-17, a granule membrane protein that moves to the plasma membrane of natural killer cells following target cell recognition. Proc Natl Acad Sci U S A. 1996;93685- 689
Link to Article
Boulland  MLKanavaros  PWechsler  JCasiraghi  OGaulard  P Cytotoxic protein expression in natural killer cell lymphomas and in alpha beta and gamma delta peripheral T-cell lymphomas. J Pathol. 1997;183432- 439
Link to Article
Iwatsuki  KHarada  HOhtsuka  MHan  GKaneko  F Latent Epstein-Barr virus infection is frequently detected in subcutaneous lymphoma associated with hemophagocytosis but not in nonfatal cytophagic histiocytic panniculitis. Arch Dermatol. 1997;133787- 788
Link to Article
Landa  NGZelickson  BDPeters  MSMuller  SAPittelkow  MR Lymphoma versus pseudolymphoma of the skin: gene rearrangement study of 21 cases with clinicopathologic correlation. J Am Acad Dermatol. 1993;29945- 953
Link to Article
Craig  AJCualing  HThomas  GLamerson  CSmith  R Cytophagic histiocytic panniculitis—a syndrome associated with benign and malignant panniculitis: case comparison and review of the literature. J Am Acad Dermatol. 1998;39721- 736
Link to Article
Perniciaro  CWinkelmann  RKEhrhardt  DR Fatal cytophagic panniculitis. J Am Acad Dermatol. 1995;321062- 1063
Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

A, Large, erythematous, violaceous, ulcerated plaque on the thigh in case 1. B, The unique clinical picture in case 3. C, Dramatic cutaneous features of subcutaneous panniculitis-like T-cell lymphoma (SPTL) in case 4. D, Slightly erythematous subcutaneous nodules on the patient's back as initial clinical presentation of SPTL in case 5.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

A, Histopathologic findings from biopsy skin specimen of case 6 showing a cellular infiltrate entirely involving the subcutaneous tissue (hematoxylin-eosin, original magnification ×12.5). B, Case 7: Dense infiltrate mainly composed of small to medium atypical lymphocytes, sometimes showing an angiocentric distribution and forming rings around the adipose tissue lobules (hematoxylin-eosin, original magnification ×400). C, Case 2: Inflammatory lymphohistiocytic infiltrate in the subcutis with tissue necrosis and karyorrhexis. Several cytophagic histiocytes are visible (hematoxylin-eosin, original magnification ×400). D, Case 1: Bone marrow biopsy specimen with prominent erythrophagia indicated by large histiocytes of multiple erythrocytes (hematoxylin-eosin, original magnification ×400).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Immunohistochemical studies showing reactivity for CD8 (A), T-cell restricted intracellular antigen 1 (TIA-1) (B), and CD68 (C) (original magnification ×400).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 4.

Polyacrylamide gel electrophoresis of polymerase chain reaction products showing the T-cell receptor (TCR) γ chain gene rearrangement in 3 cases (lanes 3, 5, and 6, which correspond to cases 4, 5, and 6, respectively, in the present study) of subcutaneous panniculitis-like T-cell lymphoma. The other patients, which are not included in this study (lanes 1, 2, 4, and 7), have polyclonal TCRγ genes. M indicates DNA molecular weight marker; C−, negative control; C+, positive control; and bp, base pairs.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Antibody Reagents Used for Immunohistochemical Studies for CHP and SPTL*
Table Graphic Jump LocationTable 2. Clinical Summary of 7 Cases of CHP and SPTL*
Table Graphic Jump LocationTable 3. Systemic Symptoms, Major Laboratory and Histopathologic Findings, and Molecular Biology Aspects of 7 Cases of CHP and SPTL*
Table Graphic Jump LocationTable 4. Immunohistochemical Studies of 7 Cases of CHP and SPTL*

References

Winkelmann  RKBowie  EJ Hemorrhagic diathesis associated with benign histiocytic, cytophagic panniculitis and systemic histiocytosis. Arch Intern Med. 1980;1401460- 1463
Link to Article
Gonzales  CLMedeiros  JBraziel  RMJaffe  ES T-cell lymphoma involving subcutaneous tissue: a clinicopathologic entity commonly associated with hemophagocytic syndrome. Am J Surg Pathol. 1991;1517- 27
Link to Article
Tanaka  KHagari  YSano  YShimano  SNamba  K A case of T-cell lymphoma associated with panniculitis, progressive pancytopenia and hyperbilirubinemia. Br J Dermatol. 1990;123649- 652
Link to Article
Ashworth  JCoady  ATGuy  RBreathnach  SM Brawny cutaneous induration and granulomatous panniculitis in large cell non-Hodgkin's (T suppressor/cytotoxic cell) lymphoma. Br J Dermatol. 1989;120563- 569
Link to Article
Burg  GDummer  RWilhelm  M  et al.  A subcutaneous delta-positive T-cell lymphoma that produces interferon gamma. N Engl J Med. 1991;3251078- 1081
Link to Article
Liddle  BJKondratowicz  GMarsden  JR Panniculitis and lymphoma. Clin Exp Dermatol. 1991;1674- 75
Link to Article
Prescott  RJBanerjee  SSCross  PA Subcutaneous T-cell lymphoma with florid granulomatous panniculitis. Histopathology. 1992;20535- 537
Link to Article
Perniciaro  CZalla  MJWhite Jr  JWMenke  DM Subcutaneous T-cell lymphoma: report of two additional cases and further observations. Arch Dermatol. 1993;1291171- 1176
Link to Article
Mehregan  DASu  WPKurtin  PJ Subcutaneous T-cell lymphoma: a clinical, histopathologic and immunohistochemical study of six cases. J Cutan Pathol. 1994;21110- 117
Link to Article
Avinoach  IHalevy  SArgov  SSacks  M Gamma/delta T-cell lymphoma involving the subcutaneous tissue and associated with a hemophagocytic syndrome. Am J Dermatopathol. 1994;16426- 433
Link to Article
Monterroso  VBujan  WJaramillo  OMedeiros  LJ Subcutaneous tissue involvement by T-cell lymphoma: a report of 2 cases. Arch Dermatol. 1996;1321345- 1350
Link to Article
Cho  KHOh  JKKim  CWHeo  DSKim  ST Peripheral T-cell lymphoma involving subcutaneous tissue. Br J Dermatol. 1995;132290- 295
Link to Article
Wang  CYSu  WPKurtin  PJ Subcutaneous panniculitic T-cell lymphoma. Int J Dermatol. 1996;351- 8
Link to Article
Chan  YFLee  KCLlewellyn  H Subcutaneous T-cell lymphoma presenting as panniculitis in children: report of two cases. Pediatr Pathol. 1994;14595- 608
Link to Article
Romero  LSGoltz  RWNagi  CShin  SSHo  A Subcutaneous T-cell lymphoma with associated hemophagocytic syndrome and terminal leukemic transformation. J Am Acad Dermatol. 1996;34904- 910
Link to Article
Sajben  FPSchmidt  C Subcutaneous T-cell lymphoma: a case report and additional observations. Cutis. 1996;58297- 302
Von den Driesch  PStaib  GSimon  MSterry  W Subcutaneous T-cell lymphoma. J Am Acad Dermatol. 1997;36285- 289
Link to Article
Dargent  JLRoufosse  CDelville  JP  et al.  Subcutaneous panniculitis-like T-cell lymphoma: further evidence for a distinct neoplasm originating from large granular lymphocytes of T/NK phenotype. J Cutan Pathol. 1998;25394- 400
Link to Article
Salhany  KEMacon  WRChoi  JK  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;22881- 893
Link to Article
Kumar  SKrenacs  LMedeiros  J  et al.  Subcutaneous panniculitic T-cell lymphoma is a tumor of cytotoxic T lymphocytes. Hum Pathol. 1998;29397- 403
Link to Article
Cordell  JLFalini  BErber  WN  et al.  Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem. 1984;32219- 229
Link to Article
Bottaro  MBerti  EBiondi  AMigone  NCrosti  L Heteroduplex analysis of T-cell receptor gamma gene rearrangements for diagnosis and monitoring of cutaneous T-cell lymphomas. Blood. 1994;833271- 3278
Vasef  MAWeiss  LMChen  YYMedeiros  LJ Gastric lymphoepithelioma-like carcinoma and jejunal B-cell MALT lymphoma with large cell transformation: demonstration of EBV with identical gene deletions in the carcinoma and large cell lymphoma. Am J Clin Pathol. 1996;105560- 566
Crotty  CPWinkelmann  RK Cytophagic histiocytic panniculitis with fever, cytopenia, liver failure and terminal hemorrhagic diathesis. J Am Acad Dermatol. 1981;4181- 194
Link to Article
Barron  DRDavis  BRPomeranz  JRHines  JDPark  CH Cytophagic histiocytic panniculitis: a variant of malignant histiocytosis. Cancer. 1985;552538- 2542
Link to Article
White Jr  JWWinkelmann  RK Cytophagic histiocytic panniculitis is not always fatal. J Cutan Pathol. 1989;16137- 144
Link to Article
Harris  NLJaffe  ESStein  H  et al.  A revised European-American classification of lymphoid neoplasm: a proposal from the International Lymphoma Study Group. Blood. 1994;841361- 1392
Peters  MSWinkelmann  RK Cytophagic panniculitis and B-cell lymphoma. J Am Acad Dermatol. 1985;13882- 885
Link to Article
Perniciaro  CWinkelmann  RKEhrhardt  DR Fatal systemic histiocytic panniculitis: a histopathologic and immunohistochemical study of multiple organ sites. J Am Acad Dermatol. 1994;31901- 905
Link to Article
Urrutia  SPiris  MAOrradre  JLMartinez  BCruz  MAGarcia-Almagro  D Cytotoxic/suppressor (CD8+, CD4+) cutaneous T-cell lymphoma with aggressive course. Am J Dermatopathol. 1990;12603- 606
Link to Article
Berti  ETomasini  DVermeer  MHMeijer  CJAlessi  EWillemze  R Primary cutaneous CD8-positive epidermotropic cytotoxic T cell lymphomas: a distinct clinicopathologic entity with an aggressive clinical behavior. Am J Pathol. 1999;155483- 492
Link to Article
Natkunam  YSmoller  BRZehnder  JLDorfman  RFWarnke  RA Aggressive cutaneous NK and NK-like T-cell lymphomas: clinicopathologic, immunohistochemical, and molecular analysis of 12 cases. Am J Surg Pathol. 1999;23571- 581
Link to Article
Medley  QGKedersha  NO'Brien  S  et al.  Characterization of GMP-17, a granule membrane protein that moves to the plasma membrane of natural killer cells following target cell recognition. Proc Natl Acad Sci U S A. 1996;93685- 689
Link to Article
Boulland  MLKanavaros  PWechsler  JCasiraghi  OGaulard  P Cytotoxic protein expression in natural killer cell lymphomas and in alpha beta and gamma delta peripheral T-cell lymphomas. J Pathol. 1997;183432- 439
Link to Article
Iwatsuki  KHarada  HOhtsuka  MHan  GKaneko  F Latent Epstein-Barr virus infection is frequently detected in subcutaneous lymphoma associated with hemophagocytosis but not in nonfatal cytophagic histiocytic panniculitis. Arch Dermatol. 1997;133787- 788
Link to Article
Landa  NGZelickson  BDPeters  MSMuller  SAPittelkow  MR Lymphoma versus pseudolymphoma of the skin: gene rearrangement study of 21 cases with clinicopathologic correlation. J Am Acad Dermatol. 1993;29945- 953
Link to Article
Craig  AJCualing  HThomas  GLamerson  CSmith  R Cytophagic histiocytic panniculitis—a syndrome associated with benign and malignant panniculitis: case comparison and review of the literature. J Am Acad Dermatol. 1998;39721- 736
Link to Article
Perniciaro  CWinkelmann  RKEhrhardt  DR Fatal cytophagic panniculitis. J Am Acad Dermatol. 1995;321062- 1063
Link to Article

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 66

Related Content

Customize your page view by dragging & repositioning the boxes below.

See Also...
Articles Related By Topic
Related Collections
PubMed Articles