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Synchronous high-grade bladder carcinoma associated with chronic lymphocytic leukemia: A rare entity in Indian literature

 Department of Pathology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India

Correspondence Address:
Vikram Narang,
Department of Pathology, Dayanand Medical College and Hospital, Ludhiana, Punjab
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_642_16

 > Abstract 

B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) is one of the common lymphoproliferative disorders with an increased risk of developing subsequent neoplasms of epithelial and mesenchymal origin. The decreased immunity and B-cell dysfunction in CLL probably accounts for this emergence of secondary malignancy. Breast, brain, skin and prostate tumors have been reported as usual coincident malignancies of CLL, while in occasional cases CLL may occur with malignancies of other solid organs, such as skin, lung, heart, and prostate. Synchronous CLL with urothelial carcinoma (UC) is an infrequent occurrence. We report this case because of its rarity in Indian literature and interesting hematological, immunophenotypic, histopathological, and cytopathological features of metastatic high-grade UC in a 61-year-old male with CLL.

Keywords: Bladder cancer, chronic lymphocytic leukemia, synchronous tumors

How to cite this URL:
Chawla J, Selhi PK, Narang V, Sood N. Synchronous high-grade bladder carcinoma associated with chronic lymphocytic leukemia: A rare entity in Indian literature. J Can Res Ther [Epub ahead of print] [cited 2020 Mar 28]. Available from: http://www.cancerjournal.net/preprintarticle.asp?id=264705

 > Introduction Top

Chronic lymphocytic leukemia (CLL) is often associated with an increased risk of developing second malignancies of epithelial and mesenchymal origin. However, coincidence of CLL and urothelial carcinoma (UC) is exceptionally rare. Only four cases of coincident CLL and bladder cancer have been reported in the literature till date. These may take place in a patient at the same time due to similar etiologies such as benzene and dyes or as a result of therapies for lymphoproliferative malignancies and UCs. The risk of coexisting malignancies in patients with CLL, which results from uncontrolled B lymphocytic proliferation in the hematopoietic organs, is greater because of the immune dysregulation and treatment with alkylating agents.[1],[2] We hereby present a case of synchronous CLL and high-grade UC with metastasis to the liver diagnosed on cytomorphology.

 > Case Report Top

A 61-year-old male presented with the complaints of fever, anaemia and thrombocytopenia with burning micturition and loss of weight. On examination, no lymphadenopathy/organomegaly was noted. On evaluation, the peripheral blood film showed leucocytosis with presence of lymphoid cells accounting for 80% and smudge cells. Flow cytometry done on the peripheral blood showed SSC-A low and CD 19 Per Cp moderate positive events to be positive for CD5, CD23, FMC-7, CD20, and ZAP70, while negative for CD10, CD25, CD103, CD38, and sIg Kappa/sIg Lambda [Figure 1]. Thus, a final diagnosis of CLL was established and he was treated with chlorambucil and steroids. On follow-up after 12 months, the patient presented with 2-week history of pain abdomen off and on associated with fever and weight loss. Multiple detector computed tomography abdomen showed diffuse irregular wall thickening of the urinary bladder with intraluminal polypoidal projection with hepatosplenomegaly and abdominal lymphadenopathy. A radiological possibility of malignancy was made. Biopsy done from thepolypoidal bladder growth showed features of high-grade papillary UC [Figure 2]. The peripheral blood film examined at that time showed absolute lymphocytosis with presence of smudge cells. On examination, inguinal lymph node was palpable and fine-needle aspiration cytology (FNAC) from the same was performed which showed singly scattered monotonous population of small lymphoid cells having coarse granular chromatin, inconspicuous nucleoli and scant amount of cytoplasm and was suggestive of CLL/small lymphocytic lymphoma. Subsequent ultrasound (USG) abdomen done after 2 months showed presence of a malignant bladder growth along with multiple hepatic and splenic lesions suspected as metastasis. USG-guided FNAC done from the liver space-occupying liver showed many singly scattered cells and papillaroid clusters of pleomorphic malignant cells having high nucleo-cytoplasmic ratio, fine nuclear chromatin and moderate amount of cytoplasm. The papillary fragments were multilayered simulating the histological appearance of UC. Many spindle-shaped, pyramidal, and racquet-shaped malignant cells with eccentric nuclei and presence of cytoplasmic vacuolations at places were also identified. Also seen were malignant non keratinized cells with a globular body and cytoplasmic process with a bulbous end-Cercariform cells [Figure 3]. In the background were seen few reactive hepatocytes.
Figure 1: Immunophenotyping showing CD5, CD19, and CD23 positivity

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Figure 2: Microphotograph shows high-grade transitional cell carcinoma (H and E, ×400)

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Figure 3: Cytological smears from liver lesion show metastatic transitional cell carcinoma (H and E, ×200)

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 > Discussion Top

The risk of coincident malignancies in patients with CLL, which consequences from uncontrolled B lymphocytic proliferation in the hematopoietic organs, is greater because of the immune dysregulation and treatment with alkylating agents.[3],[4] Breast, brain, skin, and prostate tumors have been reported as usual coincident malignancies of CLL, while in occasional cases, CLL may occur with malignancies of other solid organs, such as skin, lung, heart, and prostate.[5] UC coincident with CLL is a very rare situation with only four cases reported in literature. Furthermore, FNAC of bladder carcinoma is infrequently seen in practice with liver being a rare site of metastasis and only few studies describing the cytological features of metastatic UC are available in the literature. In our setup, three cases of UC metastasizing to the liver have been reported. Identification of metastatic transitional cell carcinoma is of utmost importance for the correct staging and management of the disease.[2] FNAC is being gradually used more for diagnosis of primary as well as metastatic tumors occurring at several sites. In patients who have a known primary site, FNAC diagnosis of metastatic tumors avoids unneccessary surgeries.[6]

Presence of multilayered papillary and papillaroid clusters of tumor cells and numerous cercariform cells in the smears are diagnostic clues toward a malignancy of urothelial origin. Cercariform cells were first described as cells having long cytoplasmic tail with flattened ends. This definition was extended to include cells having shorter, broader, but flattened and bulbous tail with a vacuole and an eccentrically placed nucleus which could be of low or high grade. Binucleate or rarely multinucleate forms havealso been observed. Renshaw et al. compared 14 cases of metastatic UC to lung with 22 cases of non-small cell lung carcinoma (NSCLC). Cercariform cells were present (eight out of nine cases) and abundant (>10 per case) in cases of UC without squamous differentiation, but were not present in any of these with squamous differentiation. In NSCLC, cercariform cells were present, but were less than 10 per case.[7],[8] In the study by Kaur et al. on cytology of metastatic UC, the tumor cells in all the seven cases were present in syncytial clusters and papillary fragments with or without fibrovascular cores. Papillary fragments made of multiple layers of tumor cells were seen in four out of seven cases. These fragments recapitulated the histopathologic appearance of UC similar to our case.[6]

 > Conclusion Top

Synchronous CLL with UC is an infrequent occurrence. Also, cytological diagnosis of metastatic UC should be made on the basis of cytomorphological findings of multilayered papillary fragments along with appropriate clinical history. Even in the absence of a clinical history, their presence should raise a suspicion of possible primary UC.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

 > References Top

Martín Hernández M, Alonso y Gregorio S, Cansino Alcaide R, Pérez-Utrilla M, Aguilera Bazán A, Regojo Zapata R, et al. Leukemic infiltration of the urinary bladder. A new case and literature review. Actas Urol Esp 2008;32:563-6.  Back to cited text no. 1
Takács I, Berkessy S, Hártó G. Primary malignant neoplasms associated with chronic lymphocytic leukemia. Postgrad Med J 1992;68:595-6.  Back to cited text no. 2
Kelsh MA, Alexander DD, Kalmes RM, Buffler PA. Personal use of hair dyes and risk of bladder cancer: A meta-analysis of epidemiologic data. Cancer Causes Control 2008;19:549-58.  Back to cited text no. 3
Pathak AB, Advani SH, Gopal R, Nadkarni KS, Saikia TK. Urinary bladder cancer following cyclophosphamide therapy for Hodgkin's disease. Leuk Lymphoma 1992;8:503-4.  Back to cited text no. 4
Ramadan KM, Kyle A, McManus D, O'Rourke D, Cuthbert RJ. Urinary bladder infiltration with chronic B-lymphocytic leukemia: Two cases with unusual presentation. Leuk Lymphoma 2006;47:1184-7.  Back to cited text no. 5
Kaur G, Bakshi P, Verma K. Fine needle aspiration cytology of metastatic urothelial carcinoma: Study of seven cases with review of literature. J Cytol 2012;29:116-20.  Back to cited text no. 6
  [Full text]  
Epstein NA. The cytologic appearance of metastatic transitional cell carcinoma. Acta Cytol 1977;21:723-5.  Back to cited text no. 7
Renshaw AA, Madge R. Cercariform cells for helping distinguish transitional cell carcinoma from non-small cell lung carcinoma in fine needle aspirates. Acta Cytol 1997;41:999-1007.  Back to cited text no. 8


  [Figure 1], [Figure 2], [Figure 3]


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