Nozomi Iwamoto

Small cell carcinoma of the urinary bladder and prostate: Cytological analyses of four cases with emphasis on the usefulness of cytological examination.

The occurrence of small cell carcinoma in the urinary bladder and prostate is rare. Only a few reports on the cytological features of small cell carcinoma of the urinary bladder in the urine specimen have been documented and, moreover, the urinary cytological features of prostate small cell carcinoma have been rarely reported. In this study, we analyzed the cytological features of four cases of small cell carcinoma of the urinary bladder and prostate, and discussed the usefulness of cytological examination of urine specimen for this type of tumor. This study included two urinary bladder and two prostate small cell carcinoma cases. Analyses of the cytological features of these cases revealed the following: i) the background was mostly inflammatory and necrotic material was also occasionally observed; ii) numerous tumor cells were present in two cases, whereas only a few neoplastic cells were observed in the remaining cases; iii) the neoplastic cells were small in size, had scant cytoplasm and a high nuclear/cytoplasmic ratio, and were arranged in small clusters or occasionally as single cells; iv) the tumor cell clusters showed prominent nuclear moldings; and v) the nuclei of the neoplastic cells were round to oval in shape with finely granular chromatin containing inconspicuous nucleoli. The cytological features of small cell carcinoma in the urine specimen are characteristic. Therefore, careful observation of the urine specimen may lead to a correct diagnosis of small cell carcinoma of the urinary bladder and, moreover, cytodiagnosis of prostate small cell carcinoma may also be possible.

Ascitic fluid due to type II herpes simplex virus infection: Report of a case with immunocytochemical confirmation

Herpes simplex virus (HSV) infection is usually observed in the oral cavity and external genitals, and HSV peritonitis is extremely rare. Herein, we report a case of type II HSV peritonitis successfully diagnosed by ascitic cytology. A 66‐year‐old Japanese man, who had been treated with steroid inhalation for 5 years due to chronic obstructive pulmonary disease, was suspected to have acute cholecystitis. Laparoscopic cholecystectomy and intraoperative cytological examination of ascitic fluid were performed. Cytological study of ascitic fluid revealed that abundant granular cell debris, degenerative cells and apoptotic bodies were present, as well as some single or multinucleated cells with ground glass nuclei. However, vivid mesothelial cells were rarely seen. Immunocytochemical staining for type II HSV was positive in single or multinucleated cells with ground glass nuclei. Therefore, a diagnosis of type II HSV peritonitis was made. This is the first reported case of type II HSV peritonitis successfully diagnosed by ascitic cytology. This report highlights that the presence of abundant cell debris, degenerative cells and apoptotic bodies, and the absence of vivid mesothelial cells are the key cytological findings to suspect HSV peritonitis, and the diagnosis can be confirmed by careful surveillance for characteristic nuclear findings of single or multinucleated cells. The frequency of opportunistic infection is increased because of the increased numbers of iatrogenic immunocompromised patients as seen in this case, therefore, cytological examination is a useful method for early detection of the causative agent of peritonitis including HSV. Diagn. Cytopathol. 2013;41:354–359.

Mediastinal seminoma: A case report with special emphasis on SALL4 as a new immunocytochemical marker

Cytological diagnosis is a valuable method for detection of mediastinal tumors, and recent reports have shown the usefulness of fine‐needle aspiration cytology for diagnosis of mediastinal tumors, including germ cell tumors. We report a case of mediastinal seminoma diagnosed intraoperatively by cytological examination of cystic fluid containing tumor cells.

Pigmented paget's disease: a diagnostic pitfall.

Paget’s disease (PD) of the breast is a rare manifestation of breast carcinoma, characterized by the presence of malignant glandular epithelial cells (Paget cells) within the squamous epithelium of the nipple and clinical manifestation of eczematous or erythematous changes of the nipple. PD is usually associated with underlying ductal carcinoma in situ or invasive ductal carcinoma, resulting from intraductal spread of carcinoma cells via lactiferous ducts into the skin of the nipple. Pigmented PD, characterized by the presence of melanin pigment in the Paget cells and/or dendritic melanocytes within the tumor nests, is a rare but distinct variant of PD. Herein, we describe the first cytological report on pigmented PD and discuss the differential diagnostic considerations. A 72-year-old Japanese female with a past history of brain infarction presented with an erosion of the right nipple. Physical examination revealed that an erythematous lesion accompanying focal erosion was present in the right nipple, however, no palpable tumor was present in her right breast. Mammography and computed tomography demonstrated no tumorous lesion in the right breast. PD was suspected clinically, thus, a scrape cytological examination was performed, and then total mastectomy was performed. Papanicolaou-stained scrape smear demonstrated that single or small clusters of atypical large cells were scattered in a background of abundant neutrophils and squamous cells without atypia. These atypical large cells had dense cytoplasm and large oval nuclei with coarse chromatin and conspicuous nucleoli. Molding of tumor cells was noted. A few atypical large cells had melanin pigment in the cytoplasm (Fig. 1). Immunocytochemical analysis revealed that these tumor cells showed positive immunoreactivity for cytokeratin (CK) 7 (Fig. 1, inset). Therefore, a cytodiagnosis of pigmented PD was made. Histopathological study of the mastectomy specimen showed that proliferation of atypical large epithelial cells with pale to slightly eosinophilic cytoplasm and large oval nuclei with conspicuous nucleoli (Paget cells) was observed within the epidermis of the nipple accompanied by focal erosion of the epidermis. Some Paget cells had melanin pigment in the cytoplasm, and dendritic melanocytes without atypia were observed within the tumor nests in the epidermis (Fig. 2). Intraductal proliferation of these carcinoma cells was also observed in the lactiferous ducts beneath the nipple (Fig. 2, inset). No invasive growth was noted. Immunohistochemically, tumor cells were positive for CK7, gross cystic disease fluid protein-15, and epithelial membrane antigen (EMA), but negative for S-100 protein, Melan A, HMB-45, and CK (34betaE12). Moreover, overexpression of HER2 protein was observed. Therefore, an ultimate diagnosis of pigmented PD was made. Scrape cytology has been recognized as a useful, easy, and non-invasive method for diagnosis of PD. Detection of cytological atypia of Paget cells can easily lead to a diagnosis of malignant tumor, however, differentiation from squamous cell carcinoma in situ of the skin (Bowen’s disease) and malignant melanoma may be difficult. Vohra et al. pointed out that long-standing lesions of PD frequently show epidermal hyperplasia with hyperparakeratosis and reactive atypia of keratinocytes, resulting in the presence of atypical keratinizing cells admixing with Paget cells. Therefore, differentiation from squamous cell Department of Clinical Laboratory Medicine and Division of Diagnostic Pathology, Shiga University of Medical Science, Shiga, Japan *Correspondence to: Mitsuaki Ishida, M.D., Ph.D., Department of Clinical Laboratory Medicine and Division of Diagnostic Pathology, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, E-mail: mitsuaki@belle.shiga-med.ac.jp Received 7 August 2012; Accepted 31 December 2012 DOI: 10.1002/dc.22977 Published online 1 March 2013 in Wiley Online Library (wileyonlinelibrary.com).

Pulmonary marginal zone B-cell lymphoma of MALT type: a cytological report with emphasis on the usefulness of detection of lymphoepithelial lesion.

Dear Dr. Bedrossian, Primary pulmonary marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissues (MALT) type (MZBL of MALT type) is a rare extranodal lymphoma, which accounts for 0.5% of all primary lung neoplasms and 70–90% of primary pulmonary lymphomas. The cytodiagnosis of MZBL of MALT type may be missed because of the rarity of this disease, as well as minimal cellular atypia and “polymorphous” appearance of lymphoma cells in the cytological specimen. Herein, we describe a case of primary pulmonary MZBL of MALT type successfully diagnosed by a brush cytological specimen, and discuss the usefulness of detection of lymphoepithelial lesion (LEL) and its cytological differential diagnostic considerations. A 71-year-old Japanese female presented with persistent chest pain. Computed tomography demonstrated a relatively well-circumscribed nodular lesion, measuring 65 mm 3 30 mm in diameter, in the left lower lung (S8) (Fig. 1). Bronchoscopy was performed under the clinical diagnosis of lung cancer or malignant lymphoma, followed by brush cytological examination and bronchial biopsy. Subsequently, the patient underwent lobectomy of the left lower lung. Her postoperative course was uneventful, and no tumor recurrence has been observed 5 months after the surgery. Papanicolaou smear of the brush cytological specimen demonstrated single or small-clustered ciliated epithelium and an abundance of lymphoid cells as well as a few macrophages (Fig. 2a). The lymphoid cells consisted of predominantly centrocyte-like cells, which were characterized by smallto medium-sized lymphocytes with slightly irregular-shaped nuclei containing small nucleoli (Fig. 2b). Careful observation revealed infiltration of centrocyte-like cells into the cluster of ciliated epithelium, which corresponded to the histopathological features of LEL (Fig. 2b, inset). Plasma cells and monocytoid B-cells were rare on Papanicolaou stained slides, but were more numerous among centrocyte-like cells on May– Gr€unwald–Giemsa stained slides (Fig. 2c). Monocytoid B-cells were characterized by medium-sized lymphoid cells with rich cytoplasm occasionally containing vacuolation in the cytoplasm and reniform nuclei harboring aggregated chromatin and smallto medium-sized nucleoli. Immunocytochemical analysis showed positive immunoreactivity for CD20 in the lymphoid cells (Fig. 2c, inset). Histopathological study of the bronchial biopsy revealed infiltration of many smallto medium-sized lymphoid cells with slightly irregular nuclei under the bronchial epithelium and lymphocytic infiltration into the ciliated epithelium (typical features of LEL) (Fig. 3). Immunohistochemical analyses showed that these lymphoid cells were positive for CD20, bcl-2, and MUM1, but negative for CD5, CD10, bcl-6, and cyclin D1 (Fig. 3, inset). Therefore, a pathological diagnosis of MZBL of MALT type was made. The histopathological features of the resected lung specimen were fundamentally the same as those of the bronchial biopsy specimen. Flow cytometric analyses of the resected lung specimen showed that CD19/CD20-positive cells were predominant (75%), and kappa-chain positive cells were also predominant (the ratio of kappa/lambda-positive cells was 22.3) (Fig. 4). In addition, fluorescence in situ hybridization demonstrated translocation of the MALT1 (18q21) gene (Fig. 4). These findings confirmed a diagnosis of MZBL of MALT type. These two authors contributed equally to this work. *Correspondence to: Mitsuaki Ishida, M.D., Ph.D., Department of Clinical Laboratory Medicine and Division of Diagnostic Pathology, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, 520-2192, Japan. E-mail: mitsuaki@belle.shiga-med.ac.jp Received 7 February 2013; revised 26 May 2013; Accepted 27 August 2013 DOI: 10.1002/dc.23039 Published online 25 October 2013 in Wiley Online Library (wileyonlinelibrary.com).