extranodal non - hodgkin 's lymphomas ( nhls ) make up approximately 25% of all cases of lymphomas , with the most common sites being gastrointestinal tract and skin . despite the increasing incidence of nhls during the last few decades , , the ovaries , uterus , and fallopian tubes are the most common sites , and only 0.12% of all nhls originate from the uterine cervix . the most common subtype of cervical nhls is diffuse large b - cell lymphoma ( dlbcl ) ; therefore , the lymphoma cells in smears typically appear as discohesive cells with scant cytoplasm , indistinct cellular membranes , irregular nuclear contours , one or more large prominent nucleoli , and irregular clearing of the nuclear chromatin . we report a rare case of dlbcl in the uterine cervix directly invading the urinary bladder , in which tumor cells were identified in the urine smears . interestingly , the voided urine smears consisted predominantly of cohesive clusters mimicking those of epithelial neoplasms arising in the urinary bladder . a 69-year - old menopausal woman presented to the urology department of our institution with a 1-month history of lower abdominal discomfort , back pain , and sudden hematuria . the patient underwent a cystoscopy procedure which revealed a smooth , large protruded lesion of the posterior bladder wall . cytological smears of voided urine were interpreted as a lymphoma with a confirmation by immucytochemistry . subsequent computed tomography ( ct ) scan and magnetic resonance imaging ( mri ) of the pelvis revealed a solid tumor ( 5.0  5.0 cm in dimension ) occupying the uterine cervix and lower part of the body [ figure 1a ] , thickening of the posterior bladder wall , and bilateral hydronephrosis . speculum examination showed a large , irregular surfaced mass with no pedicle arising from the anterior lip of the cervix . specimen from the cervix and endometrium were taken and sent to cytopathology ; cytologic interpretation was of malignant lymphoma [ figures 1b and 2a ] and pathological diagnosis was that of dlbcl , nongerminal center subtype . ( a ) pelvic magnetic resonance imaging ( mri ) shows a solid tumor occupying the uterine cervix . extensive thickening of the posterior wall of the urinary bladder is also noted ( b ) histology of biopsy from the uterine cervix shows diffuse large b - cell lymphoma ( h and e , 400 ) ( a ) cervical smear shows discohesive , large atypical lymphocytes with high nuclear - cytoplasmic ratio , finely granular chromatin , and conspicuous nucleoli ( b ) voided urine sediment shows a large aggregated cluster of degenerated lymphocytes of intermediate size ( c ) short chains of degenerated lymphocytes with nuclear molding in voided urine ( d ) discohesive large lymphocytes in voided urine , which are morphologically similar to the atypical lymphocytes in cervical smear ( pap , 600 ) the patient was hospitalized and systemic ct scan revealed slightly enlarged systemic lymph nodes . these findings were compatible with stage iv of dlbcl arising from the uterus where the cervix appears to be the primary site of disease . the patient was successfully treated with one course of cyclophosphamide , hydroxydaunorubicin , oncovin , and prednisone or prednisolone ( chop ) and five courses of chop with the drug rituximab ( r - chop ) chemotherapy . she has maintained complete remission for 3 years since the final course of the chemotherapy . the sample was centrifuged at 700 g for 3 min , fixed in 95% alcohol , and stained with may - grnwald - giemsa and papanicolaou methods . the smears consisted predominantly of large aggregates with marked cellular crowding , nuclear overlapping , and short chains composed of degenerated medium - sized round cells [ figure 2b ] . these cells contained relatively abundant cytoplasm and reduced round nuclei , resulting in a relatively low nuclear to cytoplasmic ratio . some of the cells were arranged as short chains with nuclear molding but chromatin smearing was rare [ figure 2c ] . however , discohesive fairly uniform cells were scattered around the clusters [ figure 2d ] . differentiating between epithelial neoplasms and malignant lymphoma was difficult from these findings ; therefore , we performed immunocytochemistry . we employed the polymer - peroxidase method without antigen retrieval , using histofine simple stain max - po ( nichirei biosciences , tokyo , japan ) and monoclonal antibodies against cd20 [ l26 , diluted 1/500 ; dako cytomation ( dc , glostrup , denmark ) ] , cd3 ( 2gv6 , prediluted ; roche , basel , switzerland ) , cytokeratin ( ae1/ae3 , 1/100 ; dc ) , and neuron - specific enulase ( nse ) ( bbs / nc / vi - h14 , 1/100 ; dc ) . the immunophenotype of cd20+/cd3-/cytokeratin-/nse- was consistent with a b - cell lymphoma [ figures 3a  d ] . ( a ) the intermediate - sized atypical lymphocytes are negative for cytokeratin ( b ) negative for cd3 ( c ) positive for cd20 , and ( d ) negative for nse . ( ihc , 600 ) meanwhile , the cervical smears , collected and processed by the centrifuge method , demonstrated a dispersive cellular population with single cells of intermediate to large size in a clear background . majority of these cells were discohesive and contained a moderate amount of cytoplasm and round nuclei with finely granular chromatin and a few small nucleoli . histology of the cervical biopsy revealed a highly cellular tumor of fairly monotonous lymphoid proliferation with a diffuse infiltrating pattern . immunohistochemistry on formalin - fixed paraffin - embedded sections showed that the tumor cells were positive for cd45 , cd20 , cd79a , and multiple myeloma oncogene 1 ( mum1 ) and negative for cd3 , cd5 , cd10 , cyclin d1 , bcl-2 , bcl-6 , and tdt that were consistent with dlbcl , nongerminal - center type . the sample was centrifuged at 700 g for 3 min , fixed in 95% alcohol , and stained with may - grnwald - giemsa and papanicolaou methods . the smears consisted predominantly of large aggregates with marked cellular crowding , nuclear overlapping , and short chains composed of degenerated medium - sized round cells [ figure 2b ] . these cells contained relatively abundant cytoplasm and reduced round nuclei , resulting in a relatively low nuclear to cytoplasmic ratio . some of the cells were arranged as short chains with nuclear molding but chromatin smearing was rare [ figure 2c ] . however , discohesive fairly uniform cells were scattered around the clusters [ figure 2d ] . differentiating between epithelial neoplasms and malignant lymphoma was difficult from these findings ; therefore , we performed immunocytochemistry . we employed the polymer - peroxidase method without antigen retrieval , using histofine simple stain max - po ( nichirei biosciences , tokyo , japan ) and monoclonal antibodies against cd20 [ l26 , diluted 1/500 ; dako cytomation ( dc , glostrup , denmark ) ] , cd3 ( 2gv6 , prediluted ; roche , basel , switzerland ) , cytokeratin ( ae1/ae3 , 1/100 ; dc ) , and neuron - specific enulase ( nse ) ( bbs / nc / vi - h14 , 1/100 ; dc ) . the immunophenotype of cd20+/cd3-/cytokeratin-/nse- was consistent with a b - cell lymphoma [ figures 3a  d ] . ( a ) the intermediate - sized atypical lymphocytes are negative for cytokeratin ( b ) negative for cd3 ( c ) positive for cd20 , and ( d ) negative for nse . ( ihc , 600 ) meanwhile , the cervical smears , collected and processed by the centrifuge method , demonstrated a dispersive cellular population with single cells of intermediate to large size in a clear background . majority of these cells were discohesive and contained a moderate amount of cytoplasm and round nuclei with finely granular chromatin and a few small nucleoli . histology of the cervical biopsy revealed a highly cellular tumor of fairly monotonous lymphoid proliferation with a diffuse infiltrating pattern . immunohistochemistry on formalin - fixed paraffin - embedded sections showed that the tumor cells were positive for cd45 , cd20 , cd79a , and multiple myeloma oncogene 1 ( mum1 ) and negative for cd3 , cd5 , cd10 , cyclin d1 , bcl-2 , bcl-6 , and tdt that were consistent with dlbcl , nongerminal - center type . cytologic evaluation of voided urine specimen is the most common method for the detection and diagnosis of neoplasms in the urinary bladder . typical cytologic features of bladder lymphoma are discohesive population of atypical large lymphocytes , whereas those of urothelial carcinoma ( uc ) are cohesive clusters with marked cellular crowding and nuclear overlapping . thus , neoplastic cells with lack of cohesion are generally considered as a useful finding for distinguishing lymphoma cells from epithelial cells . however , we described here an unusual cytomorphological pattern of dlbcl presenting predominantly as cohesive clusters of cells on urine smear , mimicking epithelial neoplasms . it is known that some specific types of lymphoma are prone to form aggregates in cytological specimens . for example , anaplastic large cell lymphoma and adult t - cell leukemia / lymphoma may show clusters of highly atypical cells . apart from these specific types , other types of lymphoma may form cohesive groups of degenerated neoplastic cells in the urine . indeed , some previous reports represented cases of high - grade dlbcl and low - grade lymphoma of the mucosa - associated lymphoid tissue ( malt ) type where neoplastic cells appeared as clusters with cellular crowding and cohesion , mimicking those of uc . in addition , short chains with nuclear molding of lymphoma cells may have misleading similarities to small cell carcinoma . in the urine specimen , neoplastic cells of small cell carcinoma often show loose clusters and isolated single cells with scant cytoplasm , mimicking those of lymphoma cells . these are of particular concern and may have misleading similarities to epithelial neoplasms when examining lymphoma involving the urinary bladder . compared with the centrifuge method , thin layer preparations are more cellular with better cell preservation and cleaner backgrounds . therefore , cytodiagnosis of lymphoma involving the urinary bladder should be based on the awareness that these patterns contain potential pitfalls and misleading mimics , and should be supported by adequate immunocytochemical analysis .
we report a rare case of a 69-year - old woman in whom diffuse large b - cell lymphoma ( dlbcl ) originated from the uterus and involved the urinary bladder . 
 the cervical smears of the case mostly consisted of discohesive atypical round cells , which were highly suggestive of lymphoma ; however , in voided urine smears , a majority of the cells formed large aggregates of degenerated cells , mimicking those of urothelial carcinoma ( uc ) . 
 the smears also represented some small loose clusters , in which tumor cells formed short chains with nuclear molding , mimicking those of small cell carcinoma . 
 the cytodiagnosis got definitive when we identified the atypical cells that showed cd20+/cd3-/cytokeratin-/nse- immunophenotype . 
 these are of particular concern as they may have misleading similarities to other epithelial neoplasms when examining lymphoma involving the urinary bladder . 
 accordingly , this case highlights the importance of immunocytochemistry to rule out malignant lymphoma when encountering large and/or small loose clusters of atypical round cells on urinary cytology .