Cutaneous multilobated T-cell lymphoma with aggressive course

JOURNAL

of the

A.meRiCaN A.CaDemy OF

DerMaTOLOGY VOLUME 25

NUMBER 2

PART 2

AUGUST 1991

Cutaneous multilobated T-cell lymphoma with . aggressIve course Barry D. Goldman, MD,a Merle Bari, MD,* Gary R. Kantor, MD,b Marshall E. Kadin, MD,c Bizhan Micaily, MD,d and Eric C. Vonderheid, MDb Philadelphia, Pennsylvania, and Boston, Massachusetts Cutaneous multilobated T-cell lymphoma is an uncommon variant of skin-based peripheral T-cell lymphoma typically characterized by cutaneous nodules in elderly patients and a chronic clinical course. We report a case of the disease that led to the patient's death within 2years after onset. This disease may be associated with a more aggressive clinical course than generally recognized. (J AM ACAD DERMATOL 1991;25:345-9.) Thelarge, multilobatedcelltypeofnon-Hodgkin's lymphoma was described as a distinct morphologic variant of peripheral T-cell lymphoma (PTL) by Pincus et al. l, 2 The most useful histopathologic criterion for its recognition is the presence of lymphoid cells with large multilobated or hypersegmented nuclei with relatively fine chromatin and small to inconspicuous nucleoli. Multilobated PTL has a predilection to involve extranodal sites in elderly patients (particularly the skin and bone) and a relatively favorable prognosis. In several studies of PTL,3-5 skin involvement was found in 28% of cases and approximately one third of those with skin involvement were of the large, multilobated cell type. Primary involvement of the skin with multilobated PTL, also referred to as cutaneous T-celllymphoma of the multilobated type (CMTCL), 6 occurs infrequently. To our knowledge, fewer than 20 cases have been cited in the literature. 1-9 Although most From the Department of Medicine, Lankenau Hospital, Philadelphia"; the Division of Dermatology, Hahnemann University, Philadelphiab; the Department of Pathology, Beth Israel Hospital and Harvard Medical School, Bostone; and the Department of Radiation Oncology, Hahnemann University.d Reprint requests: Eric Vonderheid, MD, Division of Dermatology, Mailstop 401, Hahnemann University, Broad and Vine Streets, Philadelphia, PA 19102. . *Private practice of Dermatology. 16/4/25505

cases of CMTCL have had chronic course and favorable prognosis, a few reports of CMTCL describe instances of aggressive disease. 3, 5, 9 We report a case of CMTCL that resulted in death within 2 years after onset. METHODS

The patient was examined and followed up in the Cutaneous Lymphoma Clinic at The Skin and Cancer Hospital of Philadelphia by one of us (E. C. V.). Skin biopsy specimens were processed for routine histopathology and immunopathology with periodate-Iysine-paraformaldehyde fixative as previously described. lO The specimens were studied with the murine monoclonal antibodies listed in Table I. CASE REPORT

A 74-year-old physician presented in June 1982 with a 3-year history of an asymptomatic eruption attributed to stasis dermatitis on both legs and a 9-month history of a rapidly enlarging tumor on the right pretibial region. The patient also had insulin-dependent diabetes and severe coronary artery disease. Physical examination revealed a plum-colored, ulcerated tumor, 3 X 5 em in diameter, with a central crust surrounded by numerous smaller violaceous nodules with minimal surface changes on the right leg (Fig. 1). Some of the smaller nodules were subcutaneous. In addition, there were several nontender lymph nodes, 1em in diameter, in the right inguinal area but no other signs of extra345

Journal of the American Academy of Dermatology

346 Goldman et al.

Fig. 1. Tumor with central crusting surrounded by violaceous nodules on right leg. cutaneous involvement. Histopathologic examination of the cutaneous tumor showed a dense infiltrate of atypical lymphoid cells throughout the dermis and subcutaneous fat with over.1ying acanthosis and absence of epidermotropism. A grenz zone was present. A few cells with large multilobated nuclei were scattered throughout the infiltrate, and numerous mitoses were seen (Fig. 2). Chromosomal studies on cells from a skin lesion suggested a clonal population with a chromosome missing from group C (hypodiploidy). Hist.opathologic examination of an inguinallymph node showed partial effacement of the lymphoid architecture by a pleomorphic large-cell lymphoma with numerous, large, multilobated cells in the paracortex (Fig. 3). Findings of routine laboratory studies, chest and lower-leg roentgenograms, computed tomography of the chest and retroperitoneum, lymphangiography, and isotopic scans of the liver, spleen, and bone were normal. A serum specimen was negative for antibody against human T lymphotropic virus type 1. The patient's condition was diagnosed as CMTCL and was treated with radiation to the right leg and hemipelvis. A complete response resulted. However, 5 months later (November 1982), the patient was hospitalized with fever, night sweats, weightloss,generalized lymphadenop-

athy, and splenomegaly. An axillary lymph node showed features of angioimmunoblastic lymphadenopathy (AIBL), and his condition responded dramatically to one course of cyclophosphamide, vincristine, and prednisone. Shortly thereafter, numerous violaceous papules, 5 to 10 mm in diameter and histopathologically identical to the original lesion, appeared on the right thigh in areas that had not been treated with radiation. The new lesions also responded to local radiation therapy. The patient remained free of apparent disease until November 1983, when numerous erythematous patches and infiltrated plaques without surface changes developed rapidly on his trunk. There were lymph nodes, 1 to 2 em in diameter, in both inguinal regions. Some lesions were annular with central clearing, resembling plaques of mycosis fungoides (Fig. 4). A skin biopsy specimen showed a nonepidermotropic infiltrate containing markedly atypicallymphoid cells that was confluent in the papillary dermis and perivascular in the reticular dermis. Immunohistochemistry showed that more than 80% of the lymphoid infiltrate had a markedly aberrant T-cell phenotype (CD3+, CD4-, CDS-, CDr, CDS-) with a high degree of expression of antigens of activation and proliferation (HLA-DR+, CD25+, CD? I +). There was no staining for the B-cell antigen HLB3 or the Ki-1 antigen (CD30-). Treatment with cyclophosphamide, vincristine, and prednisone was reinstated, but the patient's disease rapidly progressed to involve the lungs, liver, spleen, and bones, including marrow. The serum calcium level remained within normal limits throughout. The patient became pancytopenic and died in April of 1984. Permission for an autopsy was not granted. DISCUSSION In the initial 14 cases of multilobated PTL described by Pincus et al.,1,2 the disease involved lymph nodes in 10 cases; skin or subcutaneous tissue in nine cases (primary to the skin in three cases); bone in seven cases; and liver, spleen, or lung in two cases each. Most patients responded favorably to treatment, and only two died of disease. The authors concluded that the predominant extranodal distribution and favorable prognosis of this unusual morphologic variant of non-Hodgkin's lymphoma was sufficiently distinctive to warrant classification as a clinicopathologic entity. Our patient presented with localized skin tumors and regional lymphadenopathy that were typical of multilobated PTL. The infiltrate in the skin and lymph node contained scattered large lymphoid cells with multilobated nuclei and marginal nucleoli. Unfortunately, despite a good initial response to radiotherapy, his disease recurred in a more aggressive manner 1 year after an episode of AIBL. It is pos-

Volume 25 Number 2, Part 2 August 1991

Cutaneous multi/abated T-eel! lymphoma 347

Fig. 2. Densenonepidermotropic infiltrate ofatypical lymphoid cells throughout dermis and subcutaneous fat. (Hematoxylin-eosin stain; X40.) Inset shows large multilobated cell that was identified within the infiltrate. (X400.)

Table I. Monoclonal antibodies used to immunophenotype cutaneous infiltrate Antibody

Source

Cluster designation

OKT11 Leu4 Leu3 Leu1 OKT8 HLB3 Anti-HLA-DR Anti-Tac OKT9 Ki-l OKT6

Ortho BD BD BD Ortho

CD2 CD3 CD4 CD5 CDB

BD

DR CD25 CD71 CD30 CDla

*

t

Ortho

:I:

Ortho

Antigen distribution

Pan-T cell, NK cells (SRBC receptor) Pan-T cell (TCR complex) T helper/inducer, monocytes, Langerhans cells Pan·T cell, B-cell subset T suppressorI cytotoxic, NK subset Pan-B cell Class II MHC antigen Activated T cells (IL-2 receptor) Transferrin receptor Activated T and B cells, Reed-Sternberg cells Thymocytes, Langerhans cells

BD, Becton-Dickinson, Mountain View, Calif.; NK, natural killer; Ortho, Ortho Diagnostic Systems, Raritan, N J. *K. Kikuchi, Sapporo, Japan. Waldman, NIH. tH. Stein, FRG.

n.

sible that the immunoregulatory disturbances associated with AIBL may have been important in modifying the course of his disease. However, cases of multilobated PTL with unexpectedly fulminant clinical courses without associated AIBL have been reported by others. 3, 5. 9 Therefore our case illustrates that some cases of skin-based PTL (CMTCL) may also have a poor prognosis. PTLs often demonstrate a highly aberrant phenotype that does not seem to correlate with the prognosis. I I In our patient, the immunophenotype of the tumor cells during the aggressive phase of his

disease was identical to that of one patient reported by Grogan et al.,3 in whom the tumor cells expressed the T-cell receptor (CD3) but were negative for other pan-Tor T-cell subset antigens. The frequent expression of class II major histocompatibility antigens (HLA-DR) in this and other cases of CMTCL,3, 4, 8, 9,12 and the expression of the interleukin 2 receptor (CD25) and transferrin receptor (CD71) in our patient indicates that the malignant T cells were in a state of activation or proliferation. Recently, it has been suggested that expression of the Hodgkin's disease-associated antigen Ki-l

Journal of the American Academy of Dermatology

348 Goldman et al.

Fig. 3. Cluster oflargemultilobated cells in involved lymph node. (Hematoxylin-eosin stain; X400.)

(CD30) may provide better prognostic information than histopathologic criteria in skin-based PTL.13 In that series, patients with CD30+ large-celllymphomas generally presented with localized skin disease, and their conditions had a favorable prognosis (9 of 10 patients in complete remission) compared with that of CD30- lymphomas, in which generalized disease was often present at the first visit or developed rapidly thereafter ( 10 of 10 patients died, median survival 17 months). Thus the absence of CD30 expression in our case may have been prognostically significant. This work was supported by a generous donation from Mr. Leonard Rosenstein in memory of his father. REFERENCES

Fig. 4. Scattered erythematous plaques that clinically resemble mycosis fungoides on the thorax.

1. Pinkus OS, Said JW, Hargreaves H. Malignant lymphoma, T cell type: a distinct morphologic variant with large multilobated nuclei with a report of four cases. Am J Clin Pathol 1979;72:540-50. 2. Weinberg DS, Pinkus GS. Non-Hodgkin's lymphoma of large multilobated cell type: a clinicopathologic study often cases. Am J Clin Pathol 198 J ;76:1 90-6. 3. Grogan TM, Fielder K, Rangel C, et al. Peripheral T-cell lymphoma: aggressive disease with heterogeneous immunotypes. Am J Clin Pathol 1985;83:279-88. 4. Jack AS, Lee FD. Morphological and immunohistochemical characteristics of T-cell malignant lymphomas in the west of Scotland. Histopathology 1986; I0:223-34. 5. Grob JJ, Horchowski N, Tubiana N, et al. Non-lymphoblastic T-cell lymphomas with prevalent skin involvement different from mycosis fungoides or Sezary's syndrome. A

Cutaneous multi/obated T-cell lymphoma

6. 7.

8. 9.

retrospective study of 6 cases in Europe. Dermatologica 1988;177:82-97. van der Putte SCJ, Toonstra J, De Weger RA, et al. Cutaneous T-cell lymphoma, multilobated type. Histopathology 1982;6:35-54. Azar HA, Jaffe ES, Berard CW, et al. Diffuse large-cell lymphomas (reticulum cell sarcomas, histiocytic lymphomas): correlation of morphologic features with functional markers. Cancer 1980;46: 1428-41. Fattorossi A, Moretti S, Palermo A, et al. Cell surface marker studies in a patient with cutaneous multilobated Tcell lymphoma. Br J DermatoI1985;113:587-96. Wood GS, Burke IS, Horning S, et al. The immunologic and clinicopathologic heterogeneity of cutaneous lymphomas other than mycosis fungoides. Blood 1983;62:464-72.

10. Nasu K, Said J, Vonderheid E, et al. Immunopathology of cutaneous T-cell lymphoma. Am J Pathol 1985;119:43647. 11. van der Valk P, Willemze R, Meijer CJLM. Peripheral Tcell lymphomas: a clinicopathological and immunological study of 10 cases. Histopathol 1986;10:235-49. 12. van der PutteSCJ, Schuurman HJ, Toonstra J. Cutaneous T-cell lymphoma, multilobulated type, expressing membrane-differentiation antigens of precursor T-Iymphocytes. Br J Dermatol 1982;107:293-300. 13. Beljaards RC, Meijer CJLM, Scheffer E, et al. Prognostic significance of CD30 (Ki-l /Ber-H2) expression in primary cutaneous large-cell lymphomas of T-cell origin. Am J PathoI1989;135:1169-78.

Malignant schwannoma associated with xeroderma pigmentosum in a patient belonging to complementation group D Takehiko Nakamura, MD,a Tomomichi Ono, MD,a Koji Yoshimura, MD,a Tatsuyoshi Arao, MD,a Seiji Kondo, MD,b Masamitsu Ichihashi, MD,d Akira Matsumoto, MD,c and Yoshisada Fujiwara, MD, PhDc Kumamoto, Tokyo, and Kobe, Japan A 43-year-old man with xeroderma pigmentosum, XP97TO, was allocated to complementation group D. He had had moderate photosensitivity at age 1 year and freckles by age 6 but no neurologic abnormalities. Nevertheless, his fibroblasts in culture had the XP-D phenotype. They showed a sevenfold hypersensitivity to killing by 254 nm ultraviolet radiation and a diminished level (29%) of unscheduled DNA synthesis. Phototesting revealed delayed maximum erythema at 72 hours after UVB exposure and a lowered minimal erythema dose. Lentigo maligna developed on the patient's face, and a rapidly growing malignant schwannoma was found on the left trigeminal nerve. This may be the first case of a peripheral nervous tissue neoplasm in xeroderma pigmentosum. (J AM ACAD DERMATOL 1991:25;349-53.) Xeroderma pigmentosum (XP) consists of eight excision-defective complementation groups (A through H), and an XP variant group capable From the Department of Dermatology, Kumamoto University Medical School, Kumamoto;" the Department of Dermatology, School of Medicine, Tokyo Medical and Dental University, Tokyob; and the Departments of Radiation Biophysics and Dermato]ogy,d Kobe University School of Medicine, Kobe. Supported in part by agrant-in-aid for cancer research from the Ministry of Education, Science and Culture, Japan. Reprint requests: Dr. T. Nakamura, Department of Dermatology, Kumamoto University Medical School, 1-1-1 Banjo, Kumamoto 860, Japan. C

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of normally excising cyc10butane pyrimidine dimers. 1-3 Patients in certain XP groups (A, B, D, G, and H) often have cerebral and spinocerebellar abnormalities. In the major XP groups, they are found in most XP-A patients by 7 years of age. 4 - 6 Most XP-D patients show neurologic abnormalities between 7 and 20 years of age,4, 5 whereas some do not appear to have them beyond the second decade. 2, 7-9 The published reviews of Kraemer et aL 10,1 I on 830 XP patients disclosed a disproportionate increase in nervous tissue neoplasms-that is, astrocytoma, medulloblastoma, sarcoma (two cases)IO, II and glioblastoma,3, 12 in the brain and an astrocy349