Objective : Primary effusion lymphoma (PEL), which is known to occur under immunosuppressive states, is characterized mainly by proliferation of malignant cells in body cavity fluids. In the third & fourth Edition of the Classification of Tumours of Haematopoietic and Lymphoid Tissues (WHO2008), the entity of PEL was renamed as malignant lymphoma caused by human herpes virus 8 (HHV-8). We report the cytological findings of PEL, defined according to WHO2008.
Method : We carried out cytological observation, cytological measurement, and immunostaining of 3 cases of PEL diagnosed at the National Center for Global Health and Medicine Center Hospital between 2002 and 2013.
Results : The tumor cells showed a plasmablastic morphology, with large nuclei and delicate chromatin and large and prominent nucleoli, and a basophilic cytoplasm with a clear-perinuclear halo. The average cell area was 232-306 μm², the nuclear area was 145-187 μm², and the nuclear/cytoplasm ratio was 0.52-0.62. Immunohistochemically, the tumor cells were CD38- and LANA-1-positive, and CD20-negative.
Conclusion : The tumor cells of PEL were large atypical cells with plasmablastic morphology, with a basophilic cytoplasm, high N/C ratio and large round nuclei. These findings are useful for differential diagnosis of malignant effusions.

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Objective : Small cell carcinomas (SmCCs) of the urinary bladder are a rare entity with an incidence of less than 1% of all malignant neoplasms of the urinary tract. Primary SmCC of the bladder must be distinguished from invasive papillary urothelial carcinoma (IPUC) or malignant lymphoma. Immunohistochemistry of the histological specimen has been recognized as being very useful in the diagnosis of SmCC. Furthermore, recent immunohistochemical studies showed that the KIT protein is expressed in a significant percentage of bladder SmCCs.
Study Design : Four cases of bladder SmCC experienced at our hospital during the period 1988-2013 were retrospectively studied. We analyzed the clinical information, cytomorphological features, and immunohisto/cytochemical findings.
Result : The cytomorphological features of voided urine specimens closely resembled those of all other SmCC cases seen up to the present. The tumor cells of all our cases were immunocytochemically positive for c-kit. Two (50%) of them were strongly positive, one (25%) was moderately positive and one (25%) showed weak immunoreactivity.
Conclusion : Our findings showed that a significant proportion of SmCCs of the urinary bladder expressed c-kit, suggesting that immunocytochemistry to test for c-kit may be useful in the cytodiagnosis of bladder SmCC.

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Objective : At our laboratory, we decided to separate atypical squamous cells of undetermined significance (ASC-US) into ASCUS-not otherwise specified (ASCUS-NOS), associated with a low incidence of high-risk HPV infection, and ASCUS-favor dysplasia (ASCUS-D), associated with a high frequency of high-risk HPV infection. Our goal was to objectively distinguish between ASCUS-NOS and ASCUS-D using a scoring system.
Study Design : We reclassified 122 Papanicolaou smears labeled as ASC-US based on our original scoring system and compared the results with the original diagnoses and the rates of high-risk HPV in each category.
Results : Of the 122, 23 cases were classified into NILM, and none of these cases was associated with high-risk HPV infection. Thus, the rate of high-risk HPV-positive infection increased from 34.4% to 42.4% in the ASC-US cases, including 15.2% in cases of ASCUS-NOS, and 56.1% in cases of ASCUS-D.
Conclusion : Our recategorization of ASC-US cases into ASCUS-NOS and ASCUS-D using a simple scoring system for Papanicolau smears resulted in a significant difference in the rate of association with high-risk HPV infection between those subcategories. However, we could not exclude a few HPV-positive cases even in ASCUS-NOS cases after the reclassification. Thus, we concluded that it is preferable to make wide use of the ASC-US subcategories, including ASCUS-NOS, and analyze the subsequent HPV-DNA tests in the first screening for cervical cancer.

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Objective : Even after the adoption of the Bethesda System (TBS) 2001 in Japan, distinction between “atypical squamous cells of undetermined significance (ASC-US)” and other categories is still problematic in some cases.
Study Design : We subdivided ASC-US in TBS 2001 into “ASCUS not otherwise specified (ASCUS-NOS),” characterized by slight atypia, but not highly suspicious of dysplasia, and “ASCUS favoring dysplasia (ASCUS-D),” characterized by a picture suspicious of dysplasia. We compared cases of ASCUS-NOS and ASCUS-D, especially in terms of the rates of human papillomavirus (HPV) infection and the histological diagnoses.
Result : Among 14655 cytology specimens obtained by Cervex Brush (Rovers), 354 (2.4%) were labeled as ASCUS-NOS and 150 (1.0%) as ASCUS-D. Of the 115 ASCUS-NOS cases analyzed for HPV, 22 (19.1%) were HPV-positive, and of the 61 ASCUS-D cases analyzed for HPV. 33 (54.1%) were HPV-positive. Histologically, 47 of the 52 HPV-positive ASC-US cases (90.4%) were diagnosed as dysplasia.
Conclusion : It is possible to subdivide ASC-US cases into ASCUS-NOS and ASCUS-D categories, which associated with rather different HPV-positive rates. We believe that it is important to be aware of this subclassification of ASC-US for improving of our diagnostic skills.

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Background : Malignant lymphoma with more than two chromosomal translocations including MYC/8q24 is called double-hit lymphoma (DHL), the prognosis of which tends to be very poor. We report herein an autopsy case of relapsed DHL to describe the cytologic features.
Case : A 60-year-old man noticed a left neck mass two years previously. Six months later, fine-needle aspiration cytology of the left cervical lymph node was performed which showed small to large lymphoid cells with markedly irregular nuclei. The cytologic features suggested malignant lymphoma, and a left cervical lymph node biopsy was subsequently performed. The specimens showed diffuse growth of atypical lymphoid cells. Immunohistochemically, the lymphoid cells were positive for CD20, CD10, BCL6, MUM1, and BCL2. EBER was negative, Approximately 50% of cells were positive for Ki-67. Based on these findings, the pathological diagnosis of diffuse large B-cell lymphoma was established. A genetic analysis revealed the gene translocations of MYC/IGH and BCL2/IGH, indicating this particular tumor should be classified as DHL. The patient died of recurrent disease after remission with standard chemotherapy.
Conclusion : DHL with concurrent BCL2/IGH and MYC/IGH has characteristic findings in immunohistochemical and cytological morphology. These features are helpful to select the cases which need genetic analysis.

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Background : Collecting duct carcinoma of the kidney is a rare variant of renal cell carcinoma. Herein, we report the cytological findings of a case of collecting duct carcinoma of the kidney with extensive sarcomatoid change.
Case : A 50-year-old Japanese man visited a clinic for asymptomatic gross hematuria. Imaging examinations revealed a right renal tumor, and he was referred to our hospital. Calyceal lavage cytology revealed atypical glandular cells forming papillary structures, with vacuolated cytoplasm and eccentric nuclei. Under the clinical diagnosis of malignancy, right nephrectomy was performed. Imprint cytology of the right renal tumor revealed many tadpole-like cells and some sarcomatoid cells. Histology revealed collecting duct carcinoma with sarcomatoid change.
Conclusion : It is difficult to diagnose collecting duct carcinoma by urinary cytology alone. However, careful observation of the cytological specimens for the presence of both atypical glandular cells and sarcomatoid cells might lead to diagnosis of collecting duct carcinoma with sarcomatoid change.

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Background : Undifferentiated carcinoma of the thyroid usually arises from papillary or follicular carcinoma and is associated with a very poor prognosis. We report a rare case of undifferentiated carcinoma of the thyroid with a rhabdoid phenotype.
Case : A 64-year-old man presented with hoarseness of the voice caused by vocal cord paralysis. Ultrasonography revealed a large mass occupying the entire right lobe of the thyroid and ¹⁸F-FDG-PET/CT showed increased tracer uptake in this mass lesion. In preoperative aspiration cytology, highly atypical cells with bizarre nuclei were observed in a necrotic background. In addition, rhabdoid cells with globoid hyaline inclusions and abundant eosinophilic cytoplasm, eccentric nuclei and prominent nucleoli were scattered among the tumor cells. Total thyroidectomy and neck dissection were performed. Histological examination of surgically resected tissues revealed that the tumor consisted mostly of undifferentiated carcinoma with scattered foci of papillary carcinoma. In addition, rhabdoid cells were also found in the undifferentiated carcinoma component. The patient died of the disease 2 and a half months after he first presented with hoarseness.
Conclusion : A rare case of undifferentiated carcinoma of the thyroid with a rhabdoid phenotype is reported. The very poor prognosis of this rare type tumor should be borne in mind in the field of thyroid surgical pathology.

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Background : Urachal carcinoma is an extremely rare tumor. We describe a case of urachal carcinoma occurring 10 years after surgical resection of urothelial carcinoma of the urinary bladder.
Case : A 70-year-old man was admitted with hematuria. He had been diagnosed as having and been treated for urothelial carcinoma 10 years ago. CT revealed an irregular pelvic tumor at the adventitial site of the dome of the bladder. Urine cytology revealed large clusters of round to columnar cells with hyperchromatic and irregular nuclei, occasional prominent nucleoli, and intracytoplasmic lumina (ICL). These findings differed from those of the previously reported urothelial carcinomas, and based on these new cytological findings, urachal carcinoma was suspected.
Conclusion : Urachal carcinoma is very rarely encountered in cytological specimens practice, but should be considered in the event of detection of overlapping large clusters of cells, including columnar cells, with ICL.

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Background : Histiocytic sarcoma (HS) is a rare malignant neoplasm that arises from the lymph nodes, skin or intestinal tract in adults. We report a very rare case of splenic histiocytic sarcoma with the imprint cytological findings.
Case : A woman in her 60’s was found to have a solid splenic mass measuring 5 cm in diameter. Primary splenic malignant lymphoma was suspected, and spelnectomy was performed for diagnosis and treatment. The cut surface showed a well-demarcated brown-black lesion, 4.5 cm in diameter. Imprint cytology revealed large neoplastic cells in loose clusters, with lymphocytes and neutrophils in the background. The majority of cells had abundant foamy cytoplasm with multiple small vacuoles. The nuclei were large and of various shapes with irregular chromatin distribution. Some enlarged cells showed hemophagocytic activity. Histological examination revealed proliferation of large-sized neoplastic cells with abundant foamy cytoplasm and irregular nuclei. Hemophagocytosis was indentified within some enlarged cells. Immunohistochemical examination revealed that the tumor cells were positive for CD68 (PGM1), CD163 and lysozyme. Based on the findings, the tumor was diagnosed as a primary splenic histiocytic sarcoma.
Conclusion : It is necessary to refer to the clinical information and perform immunostaining because of the difficulty in making the diagnosis of histiocytic sarcoma based on the morphological findings alone.

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Background : It is very rare that malignant cells of extrauterine cancer, especially primary lung cancer, metastasize to the uterine endometrium.
Case : A 70-year-old postmenopausal female was referred to our hospital due to abnormal Pap screening result of the uterine cervix. The patient was diagnosed as having primary lung cancer 18 months previously and had been undergoing chemotherapy. The result of the cervical Pap smear retested was normal. However, the endometrial cytology showed tumor diathesis and many adenocarcinoma cell clusters, but there were no abnormal findings on endometrial curettage for histological examination, magnetic resonance imaging, and hysteroscopy. We then performed some histological and immunohistochemical examinations to clarify the origin of the endometrial malignant cells using the cell block technique. The specimens stained positively for thyroid transcription factor-1 and surfactant proteins A, and negatively for estrogen receptor and progesterone receptor. The results revealed that the endometrial abnormal cells originated from the lung cancer.
Conclusion : Immunohistochemistry tests on paraffin cell block sections are an useful procedure to make a correct diagnosis, in the cases where sufficient histological specimens cannot be obtained.

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Background : Endometrial stromal sarcoma is a rare tumor. We report a case of undifferentiated endometrial sarcoma, in which peritoneal cytology at the intraoperative consultation revealed atypical epithelioid cells.
Case : A 45-year-old woman presented with irregular vaginal bleeding and was detected to have a uterine myoma. MRI revealed an irregular polypoidal mass lesion in the anterior wall of the uterine body. Therefore, total hysterectomy with bilateral salpingo-oophorectomy was performed. Intraoperative peritoneal cytology showed small atypical cells with an epithelioid pattern of nuclear molding and cannibalism. In the imprint cytology of the resected tumor, small atypical cells were observed in a perivascular arrangement, with numerous mitoses. Immunocytochemically, the atypical cells both in the ascitic fluid and the resected tumor were positive for CD10 and vimentin, but negative for smooth muscle cell markers and neuroendocrine markers. Based on the immunocytochemical and histopathologic findings, the tumor was diagnosed as an undifferentiated endometrial sarcoma.
Conclusion : In conclusion, a uterine body tumor that resembled small cell carcinoma in intraperitoneal fluid cytology was diagnosed as undifferentiated endometrial sarcoma. Extensive morphological analysis as well as immunocytochemical analysis with a panel of immune markers, including CD10 and vimentin, may be necessary for arriving at the histopathological diagnosis of undifferentiated endometrial sarcoma.

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Background : Ovarian ependymoma is a rare neoplasm that resembles ependymoma of the central nervous system (CNS). We examined the matching features between the imprint cytological findings and histological findings of ovarian ependymoma, and the histological features of ovarian ependymoma.
Case : A 23-year-old woman underwent laparoscopic resection for a cystic lesion of the right ovary. The unilocular cyst included a nodule. We prepared imprint cytologic specimens from the nodule. Cytologically, discohesive irregular cell clusters with focal rosette formation and fibrillar cytoplasmic processes and cells arranged in sheets were observed. The cytoplasmic processes were immunocytochemically positive for GFAP. Histologically, we recognized perivascular pseudorosette formation, ependymal rosette formation, and clear cell proliferation. Immunohistochemically, the tumor was positive for GFAP. Based on the findings, we diagnosed this tumor as ovarian ependymoma.
Conclusion : Our findings suggest that the origin of the tumor and mechanism of tumor development differ between ovarian ependymoma and CNS ependymoma, because the histological and immunohistochemical findings appeared to differ between the two. An accurate diagnosis may be made rapidly based on the age of the patient, the characteristic macroscopic and cytologic findings, and the GFAP immunopositivity.

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Background : We report a rare case of Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET), assumed to arise from the uterine cervix.
Case : A 30-year-old woman presented to us with the complaint excessive menstrual and irregular vaginal bleeding. A surgically excised specimen suggested the diagnosis of ES/PNET, both histologically and immunohistochemically. Stamp cytology revealed a large number of atypical small round cells, scattered or in focal clusters, with a high N/C ratio, hyperchromatic nuclei, a fine to coarse granular chromatic pattern and small nucleoli. Rosette-like structures were identified in parts of the clusters, suggesting neuroectodermal differentiation. However, almost all atypical cells from the LBC specimen had a fine chromatic pattern, and showed a different pattern from that of the stamp cytology.
Conclusion : The granular chromatic pattern is important for suspecting neuroectodermal or neuroendocrine differentiation. The tumor cells may lack the characteristic chromatic pattern, especially when processed for LBC. A liquid-based material is available for immunocytochemical staining, and by careful evaluation of the cytological and immunocytochemical findings, the correct differential diagnosis can be reached.

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Background : Uterine angiosarcoma is a very rare disease and the endometrial and pleural fluid cytological features of this disease have not yet been clearly elucidated. Described herein is a reported case of metastatic uterine angiosarcoma to the pleura with its cytopathological features.
Case : A 62-year-old postmenopausal woman was found to have uterine endometrial thickening. The endometrial cytology and biopsy indicated a malignant spindle cell neoplasm, and total hysterectomy was performed. Histologic examination of the resected uterine specimen showed a malignant tumor composed of irregular rudimentary vascular channels and solid small nests. The tumor cells were spindle-shaped or epithelioid, and were immunohistochemically positive for CD31 and D2-40. Based on the findings, the tumor was diagnosed as a uterine angiosarcoma. Chest CT revealed a small pleural effusion on the right side 4 years after the surgery. Pleural fluid cytology showed epithelioid tumor cells in irregular clusters, gland-like arrangement and concentric layers, suggestive of vasoformative features, with some of the cells containing intracytoplasmic vacuoles. The tumor cells were immunocytochemically positive for CD31 and D2-40.
Conclusion : Careful screening for clues suggesting of vasoformative features of the tumor cells is important for the diagnosis of metastatic angiosarcoma, and immunocytochemistry is useful for differential diagnosis.

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Background : Vaginal stump fallopian tube prolapse (VSFTP) is a rare complication after a hysterectomy. The vaginal stump smear contains mature squamous cells and large clusters of small columnar cells accompanied by a leukocytic infiltration in an inflammatory background. These clusters are thought to be fallopian tubal epithelium, but no ciliated cells exist in many cases.
Case : A 38-year-old woman who underwent an abdominal hysterectomy 4 months prior sought evaluation for a brown discharge, and the vaginal stump showed a granulation tissue-like tumor. A vaginal stump scraping smear contained mature squamous cells and clusters of small non-ciliated columnar cells in an inflammatory background. An excision was performed, and a diagnosis of VSFTP was made. To determine why ciliated cells were not detected in the scraping cytopreparation, we observed an imprint and a scraping cytopreparation from the fallopian tubes of another patient. Ciliated cells were noted in the imprint cytopreparation ; however, these cells were absent in the scraping cytopreparation.
Conclusion : We conclude that the reason why most of the ciliated cells are not seen in a scraping cytopreparation in VSFTP cases is that cilia come off during scraping. The cytologic diagnosis of VSFTP is easy to establish if a sampling method is used which does not involve scraping.

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Pediatric thyroid carcinomas are rare, and associated with distinct clinical features and histological variations. Papillary carcinoma accounts for the majority of thyroid cancers in children and adolescents, and is sub-classified into the classic type, solid-follicular variant and diffuse sclerosing variant. Extrathyroidal extension and/or distant metastasis are relatively common, however, the postoperative prognoses are extremely good. In this review, we shall discuss the clinical features of papillary thyroid carcinomas of childhood, and the histopathological characteristics and genetic abnormalities associated with these cancers. A better understanding of the characteristics of childhood papillary thyroid carcinomas would aid in preoperative cytological diagnosis of thyroid nodules in children and adolescents.

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The diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) is one of the subtypes of thyroid papillary carcinoma. DSV-PTC is frequently seen in infant or young adult females, and is characterized by bilateral or hemi-lateral diffuse enlargement of the thyroid and frequent cervical node metastasis. The prognosis of DSV-RTC is poorer than that of usual papillary thyroid carcinoma. The histological findings of DSV-PTC are well known, and the tumor is characterized by diffuse lymphatic involvement of the tumor cells, frequently with squamous metaplasia, abundant psammoma bodies, marked lymphocytic infiltration and stromal fibrosis. However, there are few reports of the detailed cytological findings of DSV-PTC. In fine needle aspiration cytology of DAV-PTC, characteristic tumor cells with typical nuclear features, similar to those in usual papillary carcinoma, are seen with abundant lymphocytes, psammoma bodies and squamous metaplasia. Other findings such as solid ball-like clusters, hollow ball-like clusters, and septate cytoplasmic vacuoles or large vacuoles are also characteristic of DAV-PTC. In this article, the cytological findings of DSV-PTC are reviewed with a review of the literature, and the characteristic findings are summarized.

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Papillary thyroid carcinoma, cribriform variant (PC-CV), is found in young women and is associated with a better prognosis than conventional papillary carcinoma. The tumors are well-demarcated or encapsulated. Because cases with familial adenomatous polyposis show multiple nodules, total thyroidectomy is required. On the other hand, in sporadic cases, in which the tumors are solitary, lobectomy is recommended. Histologically, the tumor shows the cribriform pattern, no colloid, solid growth, spindle cells, morula, and peculiar nuclear clearing. Immunohistochemical analysis shows positive nuclear as well as cytoplasm staining for beta-catenin. The test for estrogen receptor (ER) expression is strongly positive. When this subtype is suspected based on cytology, I recommend immunocytochemical staining using the antibodies for beta-catenin and ER.

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The Fukushima nuclear power plant accident occurred on March 11, 2011, following the Great East Japan earthquake and tsunami. Radioactive materials, including ¹³¹I, were released into the environment after the accident. Therefore, the government initaiated the Fukushima Health Management Survey for monitoring long-term health condition of the residents in Fukushima Prefecture. In the survey, thyroid ultrasonography is scheduled for all the people under 18 years of age who were living in Fukushima Prefecture at the time of disaster. The total number of examinees is 360,000. First, thyroid ultrasonography is performed as a screening test. When abnormal findings are detected, thyroid FNAC is performed. By the end of December 2013, the cytological specimens of 75 examinees had been interpreted as Malignant or Suspicious for malignancy. Histological examination of surgically removed specimens from 33 patients revealed papillary carcinoma. At the present time, it is difficult to conclude whether these papillary carcinomas were radiation-induced or not.

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