Eosinophilia associated with a composite lymphoma

Brief reports

Histopathology 1991. 18, 363-365

ADONIS

363

030901 679100066]

BRIEF REPORT

Eosinophilia associated with a composite lymphoma J.P.MERLI0, A.DE MASCAREL, T.ASTIER-GINf, P.MICHENET, C.BEYLOT* 8z J.BEYLOT Pathology Laboratory, Internal Medicine Service, H6pital Saint-Andre, Bordeaux, *Dermatology Service, Pessac and t l N S E R M U328, Bordeaux, France Date of submission 31 July 1990 Accepted for publication 9 November 1990

We report a case of composite lymphoma heralded by a hyper-eosinophilia syndrome. Combination of immunophenotyping and gene rearrangement analysis allowed us to confirm malignancy and to detect a minor oligoclone B within a malignant T-cell predominant population. No evidence of retroviral infection was found using western blot and gene amplification techniques.

type lesions, suggesting either a reactive process or a low-grade T-cell lymphoma, AIL-type. Bone marrow biopsy showed hypercellularity with increased number of eosinophils. A skin biopsy showed no specific features. After a 3-month period of steroid therapy, during which a moderate eosinophilia presented, an overt

Keywords: composite lymphoma, gene rearrangement analysis, HTLV-I

Introduction The hyper-eosinophilic syndrome is a rare feature of malignant lymphoma. In such cases, serological and molecular studies have shown the frequent occurrence of HTLV-I infection, suggesting a role for HTLV-I in both lymphoid lymphomagenesis and eosinophil-stimulation’*2.We report a case of composite lymphoma with eosinophilia, illustrating the practical value of combined immunophenotyping and genotyping techniques. HTLV-I infection was excluded in our patient by the polymerase chain reaction (PCR) and so the significance of retroviral infection in such patients is discussed.

Case report A 3 6-year-old Caucasian male presented with a pruritic skin rash, and an eosinophilia at 17.8 x 109/1(66%)was discovered. On admission to hospital, diffuse small peripheral lymphadenopathy was noted and investigations showed eosinophilic gastroenteritis and endomyocardial fibrosis. An axillary lymph node biopsy showed angioimmunoblastic lymphadenopathy (AIL)Address for correspondence: Dr J.P.Merlio,Pathology Laboratory, HBpital Saint-Andre, F 33075 Bordeaux Cedex, France.

Figure 1. Cervical lymph node biopsy showing a high-grade lymphoma of pleomorphic morphology. H & E. x 320.

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Brief reports

Figure 3. Southern blot analysis of tumour-extracted DNA digested by BamHI and hybridized with either a the T-cell receptor 8-chain probe (Cp 2) o r b the immunoglobulin heavy chain gene (JH) probes. Lane 1: DNA extracted from the first lymph node biopsy with AIL-type lesions. Lane 2: DNA extracted from the second lymph node biopsy with high-grade pleomorphic T-cell lymphoma appearance. G = Germline configuration: R = rearranged bands.

+

Figure 2. a Predominant expression of CD 3 phenotype by the majority of tumour cells: a few cells are negative. b Expression of CD 22 antigen by some large cells with abundant cytoplasm (arrows). Frozen sections. x 350.

activity of the serum was negative. DNA extracted from both lymph nodes and examined using PCR failed to reveal any HTLV-1 proviral sequence, using primers complementary both to HTLV-1 pol (3346-3363, 3460-3477) andpx (7446-7464,7537-7554) genes3.

Discussion lymphoma appeared rapidly with generalized involvement. A cervical lymph node biopsy showed a highgrade pleomorphic T-cell lymphoma (Figure 1) with a CD 2, 3 , 4, 5, 7, UCHL-1 positive phenotype and expression of CD 25, 30 by large cells. About 30% of these large cells lacked T-cell antigens (Figure 2a) and expressed CD 22 (Figure 2b), LN-1, L-26 and MB-2, but immunoglobulin light-chain restriction could not be demonstrated. Southern blot analysis (Figure 3) showed the same clonal rearrangement of the T-cell receptor fi chain genes in the two biopsies, thus demonstrating the neoplastic nature of the first lymph node. An oligoclonal rearrangement of the immunoglobulin heavy-chain genes was present only in the material of the second biopsy, suggesting a composite lymphoma. Immunocytochemistry confirmed the presence of two separate clones with the reciprocal exclusion of T- and B-cell markers. The patient was HIV-I and HTLV-I seronegative with €?LISAand western blot methods. Reverse-transcriptase

Gene rearrangement analysis has shown its practical value in demonstrating the clonality and the neoplastic nature of the majority of AIL-type lesions4,as in the first lymph node of our patient. Thus, in T-cell-rich B-cell lymphomas5, it would allow the detection of minor oligoclones of B-cells. Therefore, composite lymphomas should be diagnosed more frequently, whereas some Bcell immunoblasts could be considered as reactive within a malignant T-cell population, as in the second lymph node biopsy of our patient. Immunophenotype analysis allowed us to distinguish two separate clones from a malignant T-cell clone bearing immunoglobulin heavychain gene rearrangement. Composite lymphoma has already been demonstrated by combination of immunophenotyping and immunogenotyping techniques in a patient presenting with marked eosinophiliah.Eosinophil activation appeared in the present case to be under the control of malignant Tcells. After intensive chemotherapy, a complete remission of 2 years with no eosinophilia was achieved.

Brief reports

Following this disease-free interval, eosinophilia heralded the recurrence of the lymphoma. A subset of lymphomas with a hyper-eosinophilia syndrome has been shown to be associated with HTLVI'e2. In three of these four patients, amplification by PCR of DNA isolated from peripheral blood mononuclear cells revealed the tux2 sequence of HTLV-I. It was therefore postulated that HTLV-I was responsible for the expansion of T-cell clones controlling eosinophilic haemopoiesis'. Indeed, no integration of proviral genome in the lymphoma cells was demonstrated, except for the case of a Japanese patient who had adult T-cell leukaemia/ lymphomaz. As in the present case, we have previously found negative results for HTLV-I by serological and PCR methods in two additional cases of CD 3 + , 4 + T-cell lymphomas arising in the course of chronic eosinophilia. Furthermore, negative results with primers complementary to the HTLV-I px gene that we used also eliminated HTLV-I1 infection3. HIV-1 infection was also excluded. Therefore, we suggest that, except in zones of endemic

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HTLV-I infection, the proliferation of the T-cells controlling eosinophil haemopoiesis may have a n origin other than HTLV-I or any retroviral infection.

References 1. Prin L. Leguern M. Ameisen JC et al. HTLV-1 and malignant hypereosinophilic syndrome. Lancet 1988; ii; 569-5 70. 2. Vukelja SJ, Weiss RB. Perry DJ. Longo DL. Eosinophilia associated with adult T cell leukemia/lymphoma. Cancer 1988: 62; 15271530. 3. Kwok S. Ehrlich G. Poiesz B. Kalish R, Sninsky JJ. Enzymatic amplification of HTLV-I viral sequences from peripheral blood mononuclear cells and infected tissues. Blood 1988: 72; 11171123. 4. Griesser H.Feller A, Lennert K. Minden, Mak TW. Rearrangement of the B chain of the T cell antigen receptor and immunoglobulin genes in lymphoproliferative disorders. 1. Clin. Invest. 1986: 78; 1179-1184. 5. Scarpa A, Bonetti F. Zamboni G. Menestrina F. Chilosi M. T-cell-rich B cell lymphoma. Am. 1. Surg. Pathol. 1989; 13; 335-337. 6. Hu E. Weiss L. Warnke R, Sklar J. Non-Hodgkin's lymphoma containing both B and T cell clones. Blood 1987: 7 0 287-292.

Histopathology 1991, 18, 365-366

ADONIS

030901679100067W

BRIEF REPORT

Glornangiosarcorna of the lower extremity H.NOER & A.KROGDAHL Department of Pathology, Aulborg Hospital, Denmark Date of submission 26 September 1990 Accepted for publication 12 November 1990

Keywords: glomus tumour, glomangiosarcoma, malignant transformation

Introduction Glomus tumours typically present as a solitary nodule in the skin of the digits and cause attacks of paroxysmal pain. Although glomus tumours are considered to be benign, a few examples of glomangiosarcomas have been r e p ~ r t e d l -This ~ . report documents an association between glomangiosarcoma and glomus tumour. Address for correspondence: Dr H.Noer, Department of Pathology, Aalborg Hospital, DK-9000 Aalborg, Denmark.

Case report A 39-year-old woman presented with lancinating pain in the left knee. The pain was localized to a distinct area on the medial side of the patella and could be triggered by touch. A subcutaneous nodule was found, and subsequently removed. There was no recurrence of tumour or symptoms at follow-up 1 3 months later. PATHOLOGICAL FINDINGS

The tumour measured 6 mm in diameter and was greybrown. It was surrounded by a n incomplete capsule and was biphasic, with typical glomus cells at the periphery and a central area of sarcoma. In some parts of the