Cytology of clear cell carcinoma of the female genital tract in fine needle aspirates and ascites

OBJECTIVE: To define the cytomorphologic features of clear cell carcinoma (CCC) of the female genital tract. STUDY DESIGN: The study consisted of four CCCs of the female genital tract in which clinical and histologic confirmation had been done. Cytologic findings were evaluated with May-Grünwald-Giemsa (MGG) stain of three cases of fine needle aspiration (FNA) material and peritoneal fluid cytology. All the FNA materials were obtained from metastatic supraclavicular lymph nodes. RESULTS: We report here the cytomorphologic features of three FNA biopsies and peritoneal fluid cytology from four patients. Primary tumors from patients with aspiration material from supraclavicular lymph nodes were located in the ovary in two patients and vagina in one. The peritoneal fluid cytology was obtained from a patient with uterine cervical tumor. Cytologic findings were similar in all preparations. The cells had abundant, pale, finely vacuolated cytoplasm with indistinct cytoplasmic membranes. The nuclei were round to oval, with fine chromatin. The characteristic feature of CCC of the genital tract was basement membrane-like substance. This hyaline extracellular material stained pinkish to purple-red in MGG preparations and was frequently observed within the cancer cell clusters. In ascitic fluid, psammoma bodies were also observed. CONCLUSION: The cytomorphologic characteristics of CCC of the genital tract are distinctive, and the entity may easily be diagnosed even at metastatic locations.     

Hydrotubation for diagnosing carcinoma in situ of the fallopian tube. A case report

BACKGROUND: Primary adenocarcinoma of the fallopian tube is rare and not diagnosed until at an advanced stage. We present a case of carcinoma in situ of the fallopian tube in which cytologic examination obtained by hydrotubation facilitated the diagnosis. CASE: A 55-year-old woman presented to Yamaguchi Red Cross Hospital for uterine cancer screening. Endometrial brush cytology revealed adenocarcinoma cells, but endometrial curettage showed no abnormal findings. We performed hydrotubation, collecting abdominal fluid by culdocentesis for cytology. The smear test showed adenocarcinoma with cells similar to those obtained by endometrial brush cytology. Laparotomy showed no abnormalities in the abdominal cavity, and pelvic washing cytology was negative. Based on the positive cytology found by hydrotubation, we performed a hysterectomy and bilateral salpingo-oophorectomy. Postsurgical histology revealed adenocarcinoma in situ of the fallopian tube. CONCLUSION: The present case suggests that cytologic examination obtained by hydrotubation may be useful in diagnosing early tubal cancer.     

Metastatic transitional cell carcinoma causing a unilateral pleural effusion: a case report

BACKGROUND: Transitional cell carcinoma (TCC) is a common neoplasm, but it is only rarely associated with serous effusions. The cytologic features of metastatic TCC in pleural effusions have been described only in occasional studies. One feature that raises the possibility of metastatic TCC in this setting is the presence of eosinophilic cytoplasmic inclusions (ECIs). CASE: Metastatic TCC was diagnosed in a pleural fluid from a 50-year-old man with a unilateral effusion. Two years previously he had been diagnosed with a poorly differentiated TCC of the urinary bladder (WHO grade 3, stage pT2 at least), and more recently he had also been diagnosed with an omental metastasis. Cytologic examination of the pleural fluid sample revealed numerous pleomorphic malignant cells, many of which were vacuolated. Numerous eosinophilic inclusions were identified within the malignant cells in the liquid based cytology (ThinPrep) preparation. Examination of the omental cake biopsy revealed similar appearances. CONCLUSION: ECIs within malignant pleural effusion fluid specimens should, if detected, raise the possibility of metastatic transitional cell carcinoma.     

Annexin A4 Is Involved in Proliferation,Chemo-Resistance and Migration and Invasion in Ovarian Clear Cell Adenocarcinoma Cells

Ovarian clear cell adenocarcinoma (CCC) is the second most common subtype of ovarian cancer after high-grade serous adenocarcinomas. CCC tends to develop resistance to the standard platinum-based chemotherapy, and has a poor prognosis when diagnosed in advanced stages. The ANXA4 gene, along with its product, a Ca⁺⁺-binding annexin A4 (ANXA4) protein, has been identified as the CCC signature gene. We reported two subtypes of ANXA4 with different isoelectric points (IEPs) that are upregulated in CCC cell lines. Although several in vitro investigations have shown ANXA4 to be involved in cancer cell proliferation, chemoresistance, and migration, these studies were generally based on its overexpression in cells other than CCC. To elucidate the function of the ANXA4 in CCC cells, we established CCC cell lines whose ANXA4 expressions are stably knocked down. Two parental cells were used: OVTOKO contains almost exclusively an acidic subtype of ANXA4, and OVISE contains predominantly a basic subtype but also a detectable acidic subtype. ANXA4 knockdown (KO) resulted in significant growth retardation and greater sensitivity to carboplatin in OVTOKO cells. ANXA4-KO caused significant loss of migration and invasion capability in OVISE cells, but this effect was not seen in OVTOKO cells. We failed to find the cause of the different IEPs of ANXA4, but confirmed that the two subtypes are found in clinical CCC samples in ratios that vary by patient. Further investigation to clarify the mechanism that produces the subtypes is needed to clarify the function of ANXA4 in CCC, and might allow stratification and improved treatment strategies for patients with CCC.     

Preoperative brush and impression cytology in ocular surface squamous neoplasms

OBJECTIVE: Preoperative cytologic diagnoses of ocular surface squamous neoplasms were evaluated and compared with histologic diagnoses. STUDY DESIGN: Impression cytology (Millipore filter paper) and brush cytology were applied to 32 patients who had conjunctival neoplasms. Papanicolaou-stained cytologic preparations and hematoxylin and eosin-stained histologic sections were examined by light microscopy. RESULTS: The brush technique was used on 27 patients; impression cytology was applied in 5 cases. Cytologic and histologic diagnoses were concordant in 26 cases. Squamous cell carcinoma or carcinoma in situ was diagnosed in 18 and dysplasia in 4 cases. Squamous metaplasia and normal-appearing conjunctival epithelial cells were diagnosed cytologically in four cases; of those histologic diagnoses, one was pterygium and three, conjunctival nevus. Four cases revealed discrepancies between the cytologic and histologic preparations. There was one false positive result, and one case was subconjunctival invasion of basal cell carcinoma of the eyelid. CONCLUSION: Impression and brush cytology are fast, cost-effective, reliable and noninvasive diagnostic tools for ocular surface squamous neoplasms. However, the brush technique has several advantages over impression cytology.     

Cytologic features of pleural effusion in apocrine sweat gland carcinoma. A case report

BACKGROUND: Carcinoma arising in the apocrine sweat glands is very rare, and there are few reports of the cytologic features. We encountered a case of metastatic apocrine carcinoma in a pleural effusion. CASE: A 46-year-old male had a dark reddish nodule in the right axillary region that was diagnosed as apocrine carcinoma of skin appendage origin. Three years after wide resection and chemotherapy, widespread metastases developed with a massive pleural effusion. Needle aspiration fluid cytology contained clusters of adenocarcinoma. Some tumor cells had abundant cytoplasm or periodic acid-Schiff-positive, coarse granules. Decapitation secretion was occasionally found on the cell surface. Immunohistochemically, the tumor cells were often positive for BRST-2 and BRST-3. CONCLUSION: Cytologic features of metastatic apocrine sweat gland carcinoma show some characteristics of adenocarcinoma. Moreover, its definitive diagnosis in a pleural effusion can be made because of retaining the characteristics of apocrine sweat gland.     

Cytology of melanotic schwannoma in a fine needle aspirate and pleural fluid. A case report

BACKGROUND: Melanotic schwannoma (MS) is a rare pigmented neural tumor most commonly occurring in the paraspinal region and involving spinal nerve roots and sympathetic ganglia. Few case reports describe the fine needle aspiration (FNA) cytology of MS. We report an additional case and for the first time describe the cytologic findings of MS in pleural fluid. CASE: A 44-year-old man presented with a 9.0-cm paraspinal mass associated with multiple lung nodules. FNA cytology of the paraspinal mass showed solitary and syncytially arranged spindled cells, with prominent nucleoli and variable amounts of cytoplasmic brown pigment. In pleural fluid, prominent isolated single cells were rounded and had a signet ring cell morphology. Tumor cells in both the aspirate and pleural fluid expressed S-100 protein and HMB-45. CONCLUSION: The FNA cytology findings of MS correlate well with the histologic findings. In pleural fluid, however, the cells are epithelioid, and some have a signet ring morphology, mimicking adenocarcinoma.     

Cytologic presentation of primary leptomeningeal sarcomatosis

The cytologic findings in the cerebrospinal fluid of a 25-year-old male who presented with a diffuse neurologic disease clinically diagnosed as meningoencephalitis are described. Primary leptomeningeal sarcomatosis was subsequently diagnosed at postmortem examination. The potential value of cerebrospinal fluid cytology as a primary diagnostic tool in this rare and unusual tumor is discussed.     

Impact of liquid-based gynecologic cytology on an HIV-positive population

OBJECTIVE: To examine the imprint of liquid-based technologies for cervicovaginal cytology on HIV-positive women, who are at high risk for cervical intraepithelial neoplasia. STUDY DESIGN: We performed a retrospective search of the cytopathology files of Johns Hopkins Hospital for the cervicovaginal cytology of HIV-positive women to examine the effect of liquid-based technology on this population. RESULTS: Significant intraepithelial lesions (SILs) (low grade SIL or greater) were identified in 24% of the conventional smears and 23% of the liquid-based cytology. Atypical squamous cells of undetermined significance (ASCUS)/atypical glandular cells of undetermined significance was diagnosed in 15% of the conventional smears and 9% of the liquid-based preparations (P = .02). In patients with ASCUS diagnoses and tissue follow-up within 7 months, significant SILs were identified in 29% with conventional smears and in 65% with liquid-based cytology. CONCLUSION: There was no statistically significant difference in the rate of SILs between conventional smears and liquid-based cervicovaginal preparations in HIV-positive women. The diagnosis of ASCUS on liquid-based cytology may have an increased likelihood of representing a significant SIL in comparison to conventional smears. For the high-risk, HIV-positive population, immediate colposcopy and biopsy may be warranted following ASCUS diagnoses on liquid-based cytology.     

Fine needle aspiration of follicular variant of papillary thyroid carcinoma presenting with pleural effusion: a case report

BACKGROUND: Malignant pleural effusion in association with mesothelioma, bronchogenic carcinoma and breast carcinoma is common, although less frequently reported with other malignancies. We report a follicular variant of papillary thyroid carcinoma (FVPTC), diagnosed on fine needle aspiration cytology (FNAC) of thyroid and lymph nodes and subsequently proved to have metastasized to the pleural cavity. CASE: A 46-year-old man presented with history of breathlessness, thyroid swelling, pleural effusion and bilateral cervical lymphadenopathy. FNAC of the thyroid swelling and the lymph nodes showed features of FVPTC with cervical lymph node metastasis. Pleural fluid examination led to suspicion of pleural involvement by metastatic deposit, confirmed by subsequent pleural biopsy. CONCLUSION: Thyroid malignancies presenting with pleural effusion are rare. In this case, although pleural fluid cytology suggested involvement of pleura, a definitive diagnosis could be rendered only on pleural biopsy. An ancillary aid, such as immunocytochemistry, could have helped establish pleural involvement on routine pleural fluid cytology alone. This case emphasizes the possible existence of rare cases of FVPTC that may be associated with a dismal prognosis. In our case, initial diagnosis of FVPTC could be made only on correlating FNA features of thyroid aspirate with those of lymph node aspirate.     

Vulvar Paget's disease. Cytologic and immunohistologic diagnosis of a case

An exfoliative smear from the vagina in a case of vulvar Paget's disease extending into the vagina and urethra was cytologically diagnosed as showing a large cell carcinoma. The malignant cells proved to be Paget cells by comparison of the cytologic specimen with subsequent biopsy specimens and by immunohistochemical studies using antibodies for glandular cytokeratin, epithelial membrane antigen, carcinoembryonic antigen and gross cystic disease fluid protein. These studies demonstrated that the Paget cell is probably of apocrine derivation. Exfoliative cytology and immunohistochemistry of exudative vulvar lesions may be helpful in the identification of Paget cells.     

Cytologic findings of lymphangioleiomyomatosis in pleural effusion: a case report

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare disease occurring almost exclusively in females of reproductive age. Patients usually present with insidious and progressive dyspnea. Episodes of hemoptysis, pneumothorax, and chylothorax may occur, and the patient progresses to eventual respiratory failure and death. The characteristic pathologic finding is proliferation of immature smooth muscle cells (LAM cells) in the lungs, lymphatics and lymph nodes of thorax and abdomen/ retroperitoneum. CASE: A 47-year-old woman with a 1-year history of LAM diagnosed on iliac lymph node biopsy presented with progressive dyspnea and pleural effusion. A chest tube was placed. The collected pleural fluid, which represented chylothorax, yielded cohesive clusters of cells consisting of 2 cell populations: an outer, discontinuous layer of flattened cells and an inner portion of ovoid spindle cells. By immunohistochemistry the inner cells stained with smooth muscle actin and were negative for keratin. CONCLUSION: The characteristic constellation of clinical findings and distinctive cytology in conjunction with immunohistochemistry staining can render the diagnosis of LAM in effusions.     

Primary pulmonary leiomyosarcoma. Report of a case diagnosed by fine needle aspiration cytology

BACKGROUND: Primary pulmonary leiomyosarcoma is a rare but important entity. We report a case diagnosed by fine needle aspiration cytology. CASE: A 73-year-old male presented with an asymptomatic, right, pulmonary, subpleural nodule detected by computed tomography during follow-up for chronic obstructive pulmonary disease. Fine needle aspiration cytology showed cellular smears with numerous single or loosely cohesive groups of spindle-shaped to round cells. The tumor cell nuclei were blunt ended (cigar shaped), with fine to fine-granular chromatin, prominent nucleoli and an irregular nuclear rim. The tumor cells were positive for desmin and negative for cytokeratin and S-100 protein by immunocytochemistry. Right upper lobectomy with lymph node dissection was performed. Pathologic diagnosis after microscopic, immunohistochemical and electron microscopic studies was leiomyosarcoma. CONCLUSION: To our knowledge, this is the first reported case of primary pulmonary leiomyosarcoma arising in the subpleural region diagnosed by fine needle aspiration cytology. Immunocytochemistry was useful in establishing the diagnosis in this case.     

Diagnostic accuracy of cytology and immunocytology in carcinomatous effusions

Background: Immunocytology substantially improves the diagnostic accuracy of conventional cytology in the diagnosis of carcinomatous effusions. Due to the unequivocal characterization of the various cell populations, a sensitivity of 92% and specificity of 100% was achieved by immunocytology, examining samples of 1234 serous effusions. Objective: Cytology plays a central role in the aetiological clarification of serous effusions. The sensitivity of this method for the diagnosis of carcinomatous effusions varies between 40% and 80%. The aim of the present study was to investigate whether immunocytology substantially improves the diagnostic quality of the cytological examination in the diagnosis of carcinomatous effusions. Method: Consecutive serous effusions were examined by conventional cytology and by immunocytology. The immunocytological examination was performed on smears, using a standard panel of three antibodies against pancytokeratin, human epithelial antigen 125 and calretinin. Results: Altogether, 1234 effusion samples were examined. A total of 603 effusions were caused by carcinomas, five by malignant mesotheliomas, 11 by malignant lymphomas and 615 by non‐malignant disorders. In conventional cytology, carcinomatous effusions were correctly diagnosed in 314 samples, corresponding to a sensitivity of 52%. In 31 specimens (5%) tumour cells without further specification were described and in 161 samples (27%) the presence of tumour cells was suspected (84% overall sensitivity). A total of 97 carcinomatous effusions (16%) were diagnosed false‐negatively and 50 (8%) of the 615 non‐malignant effusions false‐positively (92% specificity). In immunocytology, 561 carcinomatous samples were correctly diagnosed, representing a sensitivity of 93%. In six cases (1%) the presence of tumour cells was suspected. A total of 36 carcinomatous effusions (6%) were diagnosed false‐negatively (94% over‐all sensitivity). Out of the 615 non‐malignant specimens, there were no false‐positive diagnoses (100% specificity). Conclusion: Immunocytology is a simple, cost‐effective, routinely practicable method which substantially improves the diagnostic accuracy of conventional cytology in the diagnosis of carcinomatous effusions. Therefore, we recommend the use of immunocytology in all those cases where cytology on its own is not completely unequivocal.     

Clinico-cytological study of uterine papillary serous carcinoma

OBJECTIVE: The aim of this study was to determine whether or not we could distinguish uterine papillary serous carcinoma (UPSC) from other types of endometrial cancer by cytology. METHODS: We examined the cytological findings of the endometrium from five cases with UPSC and compared them with 10 cases with endometrioid adenocarcinoma, grade 1 (G1). A morphometric analysis was performed. Cytological samples from the cervix and ascites of the patients with UPSC were also reviewed. RESULTS: All five patients had FIGO stage III and IV tumours. Three patients died of the disease and two are still alive with disease. The tumour cells of UPSC tended to be shed in papillary clusters with a tumour diathesis. Psammoma bodies were seen only in UPSC. The frequency of irregular-shaped nuclei, membrane thickness and eccentric nuclei in UPSC was higher than in G1. The chromatin pattern was coarsely granular, and both anisonucleosis and bare nuclei were prominent in UPSC. Cytomorphometrically, the maximum diameter of the nuclei in UPSC was significantly greater than that in G1. The nucleoli were also more often seen in UPSC than in G1. The findings of the nuclei and nucleoli in the cervical and peritoneal fluid cytology closely resembled those in endometrial smears. The features of the cervical smears and peritoneal fluid cytology were different from those of endometrial cytology regarding clear background and small clusters of cells. CONCLUSION: As the endometrial cytology findings accurately suggested the histological diagnosis of UPSC, the diagnosis of UPSC was confirmed in this study by endometrial cytology. The cytological diagnosis of UPSC should be based on the findings of tumour diathesis, psammoma bodies and papillary clusters composed of tumour cells with enlarged nuclei and numerous nucleoli.     

Cystic degeneration in phyllodes tumor. A source of error in cytologic interpretation

OBJECTIVE: To examine problems encountered in the cytologic interpretation of phyllodes tumor (PT) with cystic degeneration and solutions thereof. STUDY DESIGN: Cystic degeneration was found in seven PTs (five benign, one low grade and one high grade). Aspirates from these yielded fluid and were usually labelled fibrocystic change on the original cytology. Smears were retrospectively analyzed, with special attention to the background, presence and nature of the epithelial and stromal fragments, foam cells and naked nuclei in the background. RESULTS: PTs with cystic degeneration on cytology showed thick fluid in the background, foamy macrophages (100%), apocrine cells (28%) and epithelial fragments, which showed nuclear atypia in two cases. On reviewing the smears, five of seven PTs had stromal fragments, albeit in small numbers. Most important, even in the absence of stromal fragments, all cases showed 5-50% naked nuclei of the fibroblastic type dispersed within the fluid background. CONCLUSION: In cases of fluid aspirates from well-defined lumps, one must search for fibroblastlike naked nuclei or stromal fragments within the fluid to clinch the diagnosis of phyllodes tumor.     

Fine needle aspiration cytology of hepatoblastoma. Recognition of subtypes on cytomorphology

OBJECTIVE: To delineate the cytomorphologic appearances of hepatoblastoma (HBL) in the largest series to date and to evaluate the feasibility of subtyping on fine needle aspiration cytology (FNAC). STUDY DESIGN: Papanicolaou- and May-Grünwald-Giemsa-stained smears of aspirates from 26 cases of HBL were analyzed by 2 observers. Histologic material, available in 15 cases, was correlated. A cytology grouping system was proposed on the basis of which all cases were classified. RESULTS: The ages of the patients ranged from 4 months to 9 years. Twenty-five cases were categorized as epithelial HBL, with epithelial fragments showing a trabecular arrangement and acinar formation in all, and extramedullary hemopoiesis in 20 cases. It was possible to differentiate fetal and embryonal areas on FNAC. Six cases showed only fetal elements (cytology group F), characterized by cells with abundant cytoplasm and a small, rounded nucleus resembling a normal fetal hepatocyte. The chromatin was finely granular, with a single, central nucleolus. Pleomorphism and mitoses were not seen, and the nuclear/cytoplasmic ratio was < or = 1/3. Fourteen cases showed, in addition to fetal elements, an embryonal component characterized by cells with scant cytoplasm, a pleomorphic nucleus, N/C ratio of > or = 3/1, coarsely granular chromatin and 2-4 angulated nucleoli. Mitoses were seen in these cells (1-4/1,000 cells). Of these 14 cases, 6 showed predominantly fetal and scant embryonal cells, while 8 cases showed fetal and embryonal components in equal amounts (cytology groups Fe and FE, respectively). Four cases showed predominantly embryonal cells (cytology group E). One case was unclassifiable (U). On histology, 8 of 14 cases were of mixed epithelial and mesenchymal type, but mesenchymal tissue was not seen on the corresponding cytology. The cytology grouping system correlated well with histology. One case was small cell undifferentiated HBL and resembled a round cell tumor without differentiation. Macrotrabecular arrangement was not seen on cytology but was seen on histology in 1 case. CONCLUSION: Epithelial HBL can be easily diagnosed in aspirates further classified into fetal and embryonal subtypes, which may be of prognostic relevance. The proposed cytology grouping system is effective in semiquantification of the observed subtypes.     

Primary malignant lymphoma of the uterine corpus diagnosed by endometrial cytology. A case report

BACKGROUND: A relatively small number of cases of primary malignant lymphoma of the uterine corpus have been reported, and it is rare for cases to be preoperatively diagnosed by cytology. CASE: A 59-year-old female experienced abnormal uterine bleeding of two months' duration. Preoperative evaluation of endometrial cytology revealed malignant cells. These cells demonstrated a rather round or oval configuration, with a markedly increased nuclear/cytoplasmic ratio, and were isolated and scattered in an inflammatory background. The nuclei were round or oval, and macronucleoli were marked. The cytologic diagnosis was malignant lymphoma. Postoperative histologic evaluation verified the presence of a primary malignant lymphoma in the uterine corpus, with a B-cell phenotype. CONCLUSION: Preoperative endometrial cytology correctly demonstrated malignant lymphoma of the uterine corpus.     

宫颈癌患者液基细胞学与组织学诊断的比较分析 仇

目的:通过对液基细胞学检测(TCT)与组织学活检的比较分析,探讨TCT出现漏诊的原因。方法:收集83例宫颈癌患者的宫颈活检组织蜡块和宫颈脱落细胞标本,组织蜡块行常规病理切片检查,脱落细胞标本进行TCT检测。结果:和组织病理学诊断结果比较,这些患者的TCT诊断漏诊18例。进行过抗HPV治疗的宫颈癌患者,其TCT漏诊率明显高于未治疗者(P<0.05)。结论:TCT在宫颈癌筛查中存在一定的漏诊,其产生的原因与癌细胞分化程度、宫颈糜烂程度、非诊断细胞的干扰、不当的采集方法及抗HPV治疗有关。