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CASE REPORT  
Year : 2012  |  Volume : 55  |  Issue : 1  |  Page : 92-96
HTLV 1 associated adult T cell lymphoma/leukemia a clinicopathologic, immunophenotypic tale of three cases from non-endemic region of south India


1 Department of Laboratory Medicine, Basvatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Andhra Pradesh, India
2 Department of Medical Oncology, Basvatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Andhra Pradesh, India

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Date of Web Publication11-Apr-2012
 

   Abstract 

Adult T cell lymphoma/leukemia is a peripheral T-cell neoplasm caused by human T-cell lymphotrophic virus-1, affects mostly adults with systemic involvement and poor prognosis. Diagnosis of adult T-Cell leukemia/Lymphoma is challenging. The clinico-pathologic and immuno-phenotypic features of the three cases will be presented.

Keywords: Adult T cell lymphoma/leukemia, human T-cell lymphotrophic virus-1, immunophenotyping

How to cite this article:
Ahmed F, Murthy S S, Mohan MK, Rajappa SJ. HTLV 1 associated adult T cell lymphoma/leukemia a clinicopathologic, immunophenotypic tale of three cases from non-endemic region of south India. Indian J Pathol Microbiol 2012;55:92-6

How to cite this URL:
Ahmed F, Murthy S S, Mohan MK, Rajappa SJ. HTLV 1 associated adult T cell lymphoma/leukemia a clinicopathologic, immunophenotypic tale of three cases from non-endemic region of south India. Indian J Pathol Microbiol [serial online] 2012 [cited 2020 Sep 24];55:92-6. Available from: http://www.ijpmonline.org/text.asp?2012/55/1/92/94870



   Introduction Top


World Health Organization (WHO) classification of hemato-lymphoid neoplasms (2008) has attributed the genesis of adult T-Cell leukemia/Lymphoma (ATLL) to a human retrovirus, the HTLV - 1, which is endemic in South Western Japan, the Caribbean basin and parts of Central Africa, and very rare in India. [1],[2] ATLL is a clinicopathologic syndrome characterized immuno-phenotypically by a mature T- Cell surface marker profile. [1] The presence of flower cells with lobulated nuclei in the peripheral blood are characteristic. However, ATLL cells may show a broad cytologic appearance. [1]


   Case Reports Top


Three cases presented with distinctive morphologic and immuno-phenotypic pattern consistent with ATLL from a non endemic region like India. The clinico-pathological data and immunophenotypic profile of the three cases are presented in [Table 1] and [Table 2].
Table 1: Summary of clinicopathologic data of three cases of adult T-cell leukemia/lymphoma

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Table 2: Immunophenotype of adult T-cell lymphoma/leukemia in patients by flow cytometry

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Case 1

A 63-year-old lady presented with history of easy fatigability since one month. Total leukocyte count was 96,000 cells/mm 3 with 59% of circulating atypical lymphocytes along with cells showing flower/lobulated nuclear configuration [Figure 1] and [Figure 2].
Figure 1: Peripheral smear of circulating atypical lymphocytes in a case 1 of ATLL (Leishman stain ×40)

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Figure 2: Peripheral smear showing the prototypic flower cells diagnostic of case 2 of ATLL (Leishman stain, oil immersion ×100)

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Immuno-phenotyping on peripheral blood is presented in [Table 2] and [Figure 3]. Based on morphologic and flow cytometry (FCM) analysis, serological test for HTLV - 1 were asked, which were positive for HTLV - 1 antibodies. X-ray skull and pelvis were unremarkable and the serum calcium levels were normal (9 mg/dl). The patient's spouse, all three sons and the daughter were subjected to HTLV - 1 serology. The husband tested positive, while other family members were negative for HTLV - 1 antibodies. On enquiry, it was ascertained that neither the patient nor the husband traveled to any known ATLL endemic areas.

The patient was started on cyclophosphamide, adriamycin, vincristine and prednisone (CHOP) along with zidovidine. After eight cycles of chemotherapy, the patient achieved initial remission; however, she later deteriorated slowly and succumbed to the disease within 12 months of initial diagnosis.
Figure 3: The gated population of neoplastic cells showed expression for T cell markers with loss of CD 7 and CD8

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Case 2

A 52-year-old male initially presented to surgical out patient department (OPD) with a swelling on the back for more than a month. Computed topographic (CT) scan revealed a soft tissue swelling on the left side at L3-L4 level with fluid around the lesion. Similar swelling was also noted on the left side over the anterior chest wall involving the 3 rd intercostal space. Histopathological examination showed unremarkable epidermis with minimal dermal activity around the vessels and adnexae while the lesion was predominantly seen within the subcutaneous region showing septal and lobular architecture. The neoplastic cells of medium size with vesicular nucleus showing irregular nuclear contours, were seen rimming around the adipocytes [Figure 4]. Mitotic activity was brisk. Immunohistochemistry showed positivity for CD3, CD5, and was negative for CD20, CD30, CD56, ALK-1, and TdT. Provisional diagnosis of cutaneous T-cell lymphoma was made. The differential diagnosis included subcutaneous panniculitis like T-cell lymphoma, peripheral T-cell lymphoma, mycosis fungoides (MF)/sezary syndrome and adult T-cell lymphoma/leukemia and further work-up was suggested. Within a week of initial diagnosis, the patient presented with shortness of breath and puffiness of face. On examination, patient was febrile and showed reduced breath sounds. Complete blood picture (CBP) showed a count of 81,000 Cells/cu.mm with 63% of atypical cells with distinctive morphology suggestive of adult T-cell lymphoma/leukemia [Figure 5]. The flowcytometry and HTLV - 1 serology corroborated with the diagnosis of adult T-cell lymphoma/leukemia. Serum calcium levels were found to be elevated (15.7 mg/dl). The patient was counseled about the treatment and prognosis, and he opted against treatment. However, he succumbed to the disease within two months of initial diagnosis.
Figure 4: Neoplastic cells in case 2 seen rimming around the adipocytes. (H and E stain ×40)

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Figure 5: Case 2- Peripheral blood findings of atypical cells (Leishman stain, oil immersion ×100)

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Case 3

A 27-year-old male presented with pain in the abdomen and vomiting since one month. He was diagnosed morphologically as having acute lymphoblastic leukemia elsewhere and referred to our institute for further management. On examination, there was abdominal rigidity and guarding. The serum amylase, lipase and calcium (8 mg/dl) were within normal limits. White blood cell (WBC) counts were 1.3 lakh/mm 3 with 92% of atypical lymphoid cells. [Figure 6] The morphology, immuno-phenotypic pattern and HTLV - 1 association correlated with the diagnosis of adult T-cell lymphoma/leukemia. Due to financial constraints, the patient opted for best supportive care only and was lost to follow-up.
Figure 6: Case 3- Circulating atypical lymphoid cells along with occasional flower cells (Leishman ×40)

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   Discussion Top


ATLL demonstrates distinct epidemiologic features, including HTLV - 1 viral oncogenesis and prevalence in endemic regions. In India, there are limited case reports. [3],[4] However, one study showed important differences in distribution of non-Hodgkin lymphoma (NHL) subtypes in India with those from the rest of the world. [5]

The differences of strain may impact ATLL incidence and populations selectively affected by this disease. It is unique from other mature T-cell lymphoma in that etiologic role of HTLV - 1 has been confirmed. Two studies on assessment of HTLV - I/II infection through a sero-survey in Saudi Arabian and Indian blood donors, by enzyme-linked immunosorbent assay (ELISA) and western blot indicated three donors to be positive for HTLV - I antibody. Two were Indian and one was a Saudi donor. [6] Another Indian study reported no cases to be positive for HTLV - 1. [7] HTLV - I infection may be sexual, vertical, and transfusion related. Serological studies of HTLV - 1 by ELISA showed that all three of our cases were positive for HTLV - I infection. In case 1, the patient and her spouse were also positive for viral antibodies suggesting possible sexual transmission of this infection. However, they have not traveled to any endemic regions of HTLV - I infection. Neither case 2 nor case 3 had any travel history or history of blood transfusion. For case 3, the possibility of early transmission from mother was considered. However, the mother was found to be deceased. It has been postulated that only 2-4% of carriers develop typical disease after a prolonged latent period of 25-30 years.

Acute subtype of ATLL is associated with leukocytosis, disseminated disease, and hypercalcemia. Case 2 alone showed elevated serum calcium levels. Skin lesions are also described in widely disseminated disease in ATLL. Smoldering variant which is a slowly progressive subtype of disease may only have skin lesion. ATLL cases may show skin lesion (15%), mostly in form of nodule/tumor, generalized papules and plaques, respectively. Two of our patients showed macular rash and one among these two cases presented with subcutaneous nodule as initial manifestation of the disease.

The leukemic cells were typically medium- to large-sized with clumped nuclear chromatin along with cells showing nuclear lobulation giving an appearance of the prototypic cells of ATLL, the flower cells which are characteristic of this disease entity. But the circulating leukemic cells may show varied morphologic appearance like blast or cells with cerebriform appearance. Bone marrow was performed in two cases and showed patchy involvement by the disease.

Flow cytometric analysis of peripheral T-cell neoplasm in leukemic phases can be used to study these malignancies based on surface antigenic expression, aberrant phenotype, which involve antigenic loss or changes in combination of various surface antigens. Gujral et al demonstrated that mature T/NK cell neoplasm constituted 4% of 380 consecutive cases that presented as leukemia. Two of these case were ATLL and showed CD4+/CD8+/CD25+ phenotype. [8] In contrast, the antigenic expression by the abnormal lymphocytes in all the three cases typically showed expression of CD2, CD3, CD4, CD5, and CD25 [Figure 7] associated with loss of CD7 and CD8. These findings parallel the findings in other studies .[9] The expression of activated T-cell marker, CD25 and loss of CD7 antigenicity is the hall-mark of ATLL.
Figure 7: Scattergram showing CD 25 expression

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Immunophenotypically as well as morphologically there can be considerable overlap of ATLL with disease like MF/Sezary syndrome, T-prolymphocytic leukemia. [10] The immunophenotype in these disorders include CD4+ phenotype. The T-PLL usually shows positivity for CD7, whereas MF/Sezary share the same immunophenotypic features with expression of CD4 and Pan T markers with loss of CD7. The morphology with association of HTLV - 1 clinches the diagnosis of ATLL.

These cases emphasize that ATLL can be seen in non endemic area like India and the diagnosis is based on clinicopathological features and demonstration of circulating antibodies towards HTLV - 1.


   Acknowledgments Top


We would like to thank Mrs G Jayshree and Mrs A Parmeshwari for the technical support rendered.

 
   References Top

1.Oshima K, Jaffe ES, Kikuchi M. Adult Tcell leukemia/ lymphoma. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. editors. WHO Classification of Tumours of haematopoietic and Lymphoid Tissues. 4th ed. Lyon, PA: IARC; 2008. p. 281-4.  Back to cited text no. 1
    
2.Bhargava R, Dalal BI. Two steps forward, one step back: 4 th WHO classification of myeloid neoplasms (2008). Indian J Pathol Microbiol 2010;53:391-4.  Back to cited text no. 2
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3.Jain P, Gupta S, Prabhash K, Patkar N, Parikh PM. Adult T cell leukemia: A typical case from India. Indian J Cancer 2008;45:72-3.  Back to cited text no. 3
[PUBMED]  Medknow Journal  
4.Khadikar UN, Matai AM, Chakrapani M, Prasak. Rare association of papillary carcinoma of thyroid with Adult T Cell lymphoma - Leukemia. Indian J Pathol Mirobiol 2010;55:125-7.  Back to cited text no. 4
    
5.Naresh KN, Srinivas V, Soman CS. Distribution of various subtypes of non-Hodgkin's lymphoma in India: A study of 2773 lymphomas using R.E.A.L. and WHO Classifications. Ann Oncol 2000;11Suppl1:63-7.  Back to cited text no. 5
    
6.Ul-Hassan Z, Al-Bahrani AT, Panhotra BR. Prevalence of human T-lympho-tropic virus type I and type II antibody among blood donors in Eastern Saudi Arabia. Saudi Med J 2004;25:1419-22.   Back to cited text no. 6
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7.Agrawal A, Parmar BH, Gajjar MD, Bhatnagar NM. Study of prevalence of Human T cell lymphoma virus-I/II in West India blood donors and high risk persons. Asian J Transfus Sci 2010;4:135-6.   Back to cited text no. 7
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8.Gujral S, Polampalli S, Badrinath Y, Kumar A, Subramanian PG, Nair R, et al. Immunophenotyping of mature T/NK cell neoplasm presenting as leukemia. Indian J Cancer 2010;47:189-93.  Back to cited text no. 8
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9.Suzumiya J, Ohshima K, Tamura K, Karube K, Uike N, Tobinai K, et al. The international prognostic index predicts outcome of adult T-Cell leukemia/lymphoma. Analysis of 126 patients from the international peripheral T cell lymphoma project. Ann Oncol 2009;20:715-21.  Back to cited text no. 9
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10.Foucar K. Mature T-Cell leukemia including T-Prolymphocytic leukemia, Adult T-Cell leukemia/lymphoma and Sezary syndrome. Am J Clinic Pathol 2007;127:496-510.  Back to cited text no. 10
    

Top
Correspondence Address:
Faiq Ahmed
Department of Pathology Laboratory Medicine, Basvatarakam Indo American Cancer Hospital and Research Institute, Rd No 14, Banjara Hills, Hyderabad - 500 034, Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.94870

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
 
 
    Tables

  [Table 1], [Table 2]

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