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Year : 2014  |  Volume : 57  |  Issue : 1  |  Page : 133-135
Testicular swelling: A rare manifestation of chronic lymphocytic leukemia presenting with Richter's syndrome

1 Department of Pathology and Lab Medicine, Medanta The Medicity, Gurgaon, Haryana, India
2 Department of Medical Oncology and Hematology, Medanta The Medicity, Gurgaon, Haryana, India

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Date of Web Publication17-Apr-2014


Richter syndrome (RS) represents the clinico-pathologic transformation of indolent lymphomas to an aggressive lymphoma, most commonly diffuse large B-cell lymphoma. Majority of the patients have a previous diagnosis of Chronic Lymphocytic Leukemia and the median time to transformation is 2-4 years. De novo RS is extremely uncommon. RS frequently arises in the lymph nodes or bone marrow and rarely presents with extra nodal involvement, common sites being the gastrointestinal tract, eye, central nervous system, lung and kidney. Involvement of testis by RS is extremely rare and we came across only one such reported case in the literature.
We are reporting this case as our patient presented with de novo RS at an extremely uncommon extra nodal site, testis.

Keywords: Chronic lymphocytic leukemia, de novo, Richter syndrome, testis

How to cite this article:
Jha B, Dass J, Sachdev R, Bhargava R. Testicular swelling: A rare manifestation of chronic lymphocytic leukemia presenting with Richter's syndrome. Indian J Pathol Microbiol 2014;57:133-5

How to cite this URL:
Jha B, Dass J, Sachdev R, Bhargava R. Testicular swelling: A rare manifestation of chronic lymphocytic leukemia presenting with Richter's syndrome. Indian J Pathol Microbiol [serial online] 2014 [cited 2022 Jan 22];57:133-5. Available from: https://www.ijpmonline.org/text.asp?2014/57/1/133/130925

   Introduction Top

Richter syndrome (RS) represents the clinico-pathologic transformation of chronic lymphocytic leukemia (CLL) to an aggressive lymphoma. [1],[2],[3] RS is mostly represented by diffuse large B-cell lymphoma (DLBCL). [1],[2] RS is characterized by development of B-symptoms, sudden clinical deterioration and a rapid increase in the size of lymphoid mass at one site. [1],[2],[3],[4] Majority of patients are known cases of CLL, [2],[4] but patients may present occasionally with de novo RS. [3],[6] RS frequently arises in lymph nodes or bone marrow and disseminates to other organs. Only rarely, it presents with extra nodal involvement including gastrointestinal tract, lung, pleura, oropharynx, bone, skin and central nervous system. [7] Testicular involvement, as seen in our patient, is extremely rare and we came across only one such reported case in the literature. [9]

   Case Report Top

This was a case report of a 52-year-old male patient presented with complaints of low grade fever, pain abdomen and anorexia for 15-20 days. There was no peripheral lymphadenopathy or organomegaly. Peripheral blood counts were: White blood cell-38 × 10 9 /L, hemoglobin (Hb)-121 g/L; platelet count-204 × 10 9 /L. Peripheral smear showed absolute lymphocytosis with mature morphology (neutrophils 26%, lymphocytes 73%, eosinophils 0%, basophils 0%, monocytes 2% respectively) with presence of smudge cells [Figure 1]. Bone marrow revealed presence of similar small mature lymphocytes accounting for ~51% of nucleated cells. Flow cytometric immunophenotyping on peripheral blood showed ~45.23% lymphocytes of which 70.8% cells were B lymphoid cells (CD 19+ ). The B lymphoid cells showed co-expression of CD5 and CD23. There was moderate expression of CD22, dim expression of immunoglobulin M, heterogeneous expression of CD20 and a dim expression of kappa light chain. These cells were negative for FMC7, CD10, CD123, CD38. Overall pattern was consistent with CLL [Figure 2].
Figure 1: Peripheral smear showing lymphocytosis and smudge cells (Giemsa, ×400)

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Figure 2: Flow cytometry on peripheral blood, CD19 positive lymphocytes are gated. These are positive for CD5 and CD23, FMC-7 negative and CD22 dim positive

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Lactic acid dehydrogenase (LDH) was raised 1963 U/L (normal range 313-618 U/L).

Patient gave a history of painless testicular enlargement for which orchidectomy had been done 15 days back. The blocks of orchidectomy were reviewed and showed effacement of the testicular architecture by a diffuse large atypical lymphoid infiltrate with individual cells having moderate cytoplasm, vesicular nuclei and conspicuous nucleoli. Normal seminiferous tubules were noted. Brisk mitosis with few areas of necrosis was seen [Figure 3]a. The lymphoid cells were positive for leukocyte common antigen, CD20 [Figure 3]b, MUM1 [Figure 3]c and negative for CD3, CD5, CD10, CD23, CK and Bcl-6 on immunohistochemistry. In view of characteristic morphology and immunohistochemical profile, a diagnosis of DLBCL (non-Germinal center subtype) was made.
Figure 3: (a) Section shows an infiltrate of large atypical cells, normal seminiferous tubules are seen (H and E, ×200). (b) The neoplastic cells are diffusely CD20 positive (CD20 immunostain, ×400). (c) The neoplastic B lymphoid cells also show diffuse MUM-1 positivity (MUM- 1 immunostain, ×400). (d) Computed tomography Abdomen: Mass lesion in retroperitoneum encasing the inferior vena cava, bilateral renal vessels and aorta

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In the meantime, computed tomography chest and abdomen was done and revealed a mass lesion in retroperitoneum encasing the inferior vena cava, bilateral renal vessels and aorta, few enlarged hilar lymph nodes with bilateral pleural effusion [Figure 3]d.

A final diagnosis of a CLL with de novo RS was established.

In view of development of RS, the patient was started on R-CHOP(Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone. After 4 cycles of chemotherapy and 10 month follow-up, the patient has normal physical examination and normal complete blood cell counts.

   Discussion Top

Maurice Richter first described RS in 1928 as development of aggressive large cell lymphoma on a setting of prior CLL. [1],[2] The incidence of RS from CLL has been estimated to be in the range of 2-9% respectively. [1],[2],[3] It is characterized by rapid lymph node enlargement, splenomegaly, hepatomegaly, fever, weight loss and is associated with a rapid fatal outcome. [1],[2],[3],[4] RS frequently arises in the lymph nodes or bone marrow. Involvement of extra nodal sites are rare and include the gastrointestinal tract (5.1%), lung (2.5%), pleura (10.2%), oropharynx (7.7%), bone (2.5%) and also the central nervous system (12.8%) respectively. [3] Trisomy 12 and chromosome 11 abnormalities, as well as multiple genetic defects have been described in patients with RS. Mutations of the p53 gene, p16INK4A, loss of p27 expression, deletion of retinoblastoma, increased copy number of C-MYC and decreased expression of the A-MYB gene, have been described. [1] Recent studies have suggested that development of RS may be related to evolution of an abnormal clone unrelated to the underlying CLL clone. [1],[7] Clearly identifiable risk factors for the development of RS are lacking and its development has been shown to be independent of the duration of the disease, type of therapy or response to therapy. [3] However, CD38 expression (negative in our case), lymph node size, advanced Binet stage, deletion 13q14 and IGHV4-39 usage have been identified as an independent risk factors of RS and may help in predicting RS at CLL diagnosis. [3]

The majority of patients have a prior diagnosis of CLL, but a patient may present occasionally with de novo RS. [1],[7] Median time from the diagnosis of CLL/small lymphocytic leukemia to transformation has been in the range of 2-4 years. [5],[6] Our patient presented with de novo RS with CLL.

There are no laboratory findings that are specific for RS. Anemia (Hb < 110 g/L) is seen in about 50% of cases and thrombocytopenia (platelet count < 100 × 10 9 /L) in 43%. [8] Around 80% of patients present with LDH levels twice the upper limit of normal, in contrast with CLL in which only 8% of cases have elevated LDH. [5] Our patient also presented with elevated LDH with only extranodal involvement in the absence of cytopenias.

Diagnosis of RS requires histopathological confirmation and is generally made on biopsy of a rapidly enlarging lymph node or extranodal organ (testis in our case). [8]

The clinical course of RT is rapidly progressive, with a median survival of 5-8 months. [1],[5],[8]

Therapeutic strategies include intensive chemotherapy, immunotherapy and stem cell transplantation. The response rates range from 5 to 43% and the median survival duration ranges from 5 to 8 months. [1],[5],[8] In general, response to chemotherapy is poor unlike our case. We managed our patient aggressively with chemoimmunotherapy and he is clinically and radiologically stable on 10 months of follow-up.

Ours is only the second report of CLL transformation to a DLBCL affecting the testis, extremely uncommon site for this entity. This could represent clonal evolution of CLL or a second malignancy.

   Conclusion Top

CLL patient showing worsening systemic symptoms and extra-nodal involvement should arouse a suspicion of RS which should be histopathologically confirmed and treated aggressively. Only rarely, patients may present with de novo RS like our patient. Such patients may respond to early aggressive therapy.

   References Top

1.Tsimberidou AM, Keating MJ. Richter syndrome: Biology, incidence, and therapeutic strategies. Cancer 2005;103:216-28.  Back to cited text no. 1
2.Yee, KW, O'Brien, SM, Giles, FJ. Richter's syndrome: biology and therapy. Cancer J 2005; 11:161.   Back to cited text no. 2
3.Rossi D, Cerri M, Capello D, Deambrogi C, Rossi FM, Zucchetto A, et al. Biological and clinical risk factors of chronic lymphocytic leukaemia transformation to Richter syndrome. Br J Haematol 2008;142:202-15.  Back to cited text no. 3
4.Swords R, Bruzzi J, Giles F. Recent advances in the diagnosis and therapy of Richter's syndrome. Med Oncol 2007;24:17-32.  Back to cited text no. 4
5.Robertson LE, Pugh W, O'Brien S, Kantarjian H, Hirsch-Ginsberg C, Cork A, et al. Richter's syndrome: A report on 39 patients. J Clin Oncol 1993;11:1985-9.  Back to cited text no. 5
6.Harousseau JL, Flandrin G, Tricot G, Brouet JC, Seligmann M, Bernard J. Malignant lymphoma supervening in chronic lymphocytic leukemia and related disorders. Richter's syndrome: A study of 25 cases. Cancer 1981;48:1302-8.  Back to cited text no. 6
7.Cherepakhin V, Baird SM, Meisenholder GW, Kipps TJ. Common clonal origin of chronic lymphocytic leukemia and high-grade lymphoma of Richter's syndrome. Blood 1993;82:3141-7.  Back to cited text no. 7
8.Tsimberidou AM, O'Brien S, Khouri I, Giles FJ, Kantarjian HM, Champlin R, et al. Clinical outcomes and prognostic factors in patients with Richter's syndrome treated with chemotherapy or chemoimmunotherapy with or without stem-cell transplantation. J Clin Oncol 2006;24:2343-51.  Back to cited text no. 8
9.Houdelette P, Dumotier J, Hauteville D, Pierre C, Berthod N. Richter's syndrome with testicular localization J Urol (Paris) 1989;95:507-8.  Back to cited text no. 9

Correspondence Address:
Bhawna Jha
B-10, Chattarpur Enclave, Phase 2, New Delhi - 110 074
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.130925

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  [Figure 1], [Figure 2], [Figure 3]

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