Diagnostic pitfalls of peritoneal washing cytology and the role of cell blocks in their diagnosis

Mesothelial cell hyperplasia, collagen balls, endometriosis, and endosalpingiosis are diagnostic pitfalls on peritoneal washing cytology in women who present with gynecologic lesions. Over an 8-month period, the peritoneal washings from 10 patients undergoing gynecologic surgery for presumed malignancy showed unusual cytologic findings, several of which posed diagnostic difficulties. The washings from four patients with ovarian carcinomas were cellular and contained clusters and strips of cells with cytologic atypia mimicking malignancy. Confirmation of their benign mesothelial origin was confirmed on immunohistochemistry utilizing cell block preparations. In two cases of endometrial endometrioid carcinoma, the washings contained several clusters of cells surrounding and/or admixed with a globular substance. Due to their similarity to endometrial cells, immunohistochemistry was performed on cell block preparations. The cells were positive for cytokeratin and negative for carcinoembryonic antigen and B72.3, confirming their mesothelial origin. In one case, clinically presumed to be a malignant mass, the washings contained tight clusters of cells with mild cytologic atypia admixed with hemosiderin-laden macrophages. In conjunction with the cell block findings, a diagnosis of endometriosis was made. Extensive endometriosis was found on the surgically resected specimen. In two cases, strips of ciliated epithelial cells resembling tubal epithelium were present on the cytologic and cell block preparations, consistent with endosalpingiosis. The peritoneal washings in one case contained several clusters and balls of atypical cells surrounding microcalcifications on cell block preparation. Since calcification within groups of cells in peritoneal washings always raised the possibility of malignancy, a serous carcinoma of the ovary, particularly of borderline malignancy, would have to be excluded. Fortunately, the resected specimen was free of tumor and showed calcified endosalpingiosis on the ovarian surface. Preparation of cell blocks from peritoneal washings is of value in the work-up and management of patients who present with cytologic mimickers of malignancy on fluid cytology.     

Cytology of ductal lavage fluid of the breast

The cytologic evaluation of nipple aspirate fluids has been shown to identify women at increased risk for developing breast cancer. One limitation of this assay is the often scant cellularity of the specimen. An improved technique, ductal lavage, utilizes a microcatheter inserted into individual breast ducts to collect large numbers of cells for cytologic evaluation. Epithelial cells in ductal lavage fluids can be categorized as benign, malignant, or showing mildly or markedly atypical changes. The cell characteristics which were most helpful in identifying abnormal cells were related to cell arrangement, cell size, nuclear size, and size variation, nuclear membrane irregularity, chromatin granularity, and the presence of large nucleoli. Cell size, nuclear size variation, and large nucleoli were the most robust features, as determined by agreement between two pathologists. Moderate cell enlargement and the presence of large nucleoli were the features selected by structured tree analysis for classifying the specimens into the diagnostic groups. The similarity of the cytology of ductal lavage fluid to nipple aspirate fluid strongly suggests that these specimens will also be useful for predicting breast cancer risk.     

Murine experimental leprosy: Evaluation of immune response by analysis of peritoneal lavage cells and footpad histopathology

This study evaluated the immune response of nude and BALB/c mice inoculated in the footpads (FP) with Mycobacterium leprae after 3, 5 and 8 months. At each timepoint peritoneal cells, peripheral blood, FP and popliteal lymph nodes (PLN) were collected. Peritoneal cell cultures were performed to measure the H₂O₂, O₂^?, NO, IL‐2, IL‐4, IL‐10, IL‐12, IFN‐γ and TNF levels. Serum levels of anti‐PGL‐I antibodies were also quantified. The results showed that the infection was progressive in nude mice with bacterial multiplication, development of macroscopic lesions in the FP and presence of bacilli in the PLN at 8 months. In BALB/c mice, the infection reached a plateau of bacillary multiplication at 5 months and regressed at 8 months. Histopathological analysis of FP revealed a mononuclear inflammatory infiltrate with a large number of neutrophils at 5 months, with a higher number in nude mice. At 8 months, the number of neutrophils decreased and the infiltrate was predominantly mononuclear in both mouse strains. There was no H₂O_2, O₂^?, IL‐2, IL‐4, IL‐10 and IFN‐γ production in the course of infection in nude mice; however, in BALB/c, O₂^? and IL‐12 production was higher at 5 months and NO, IFN‐γ and TNF production was higher at 8 months when there was a decrease in the number of bacilli. The level of anti‐PGL‐I antibodies was higher in BALB/c mice. Thus, nude and BALB/c mice can be used as experimental models for the study of various aspects of leprosy.     

Pulmonary mesothelioma in bronchioalveolar lavage: a case report

Mesothelioma is a neoplasm arising from the mesothelial cells lining the body serosal surfaces. The frequent primary sites include the pleura followed by the peritoneum and rarely the pericardium. Pleural mesothelioma encases the lung and fills the pleural space, which limits the lungs' ability to expand. The initial diagnosis requires the presence of characteristic clinical, radiological, and pathological features. A thorough review of the English language literature found no reports where a diagnosis of mesothelioma was made on material originating from bronchioalveolar lavage (BAL). We report a case of lung parenchymal involvement by mesothelioma shedding cells in BAL specimen.     

子宫内膜癌腹水细胞学阳性的危险因素和预后意义

目的探讨子宫内膜癌患者腹水细胞学阳性的危险因素和预后意义。方法收集2005年1月1日至2010年12月31日北京协和医院收治的486例初治子宫内膜癌患者的临床资料进行回顾性分析,单因素及多因素分析腹水细胞学阳性对预后的影响。结果 1)子宫内膜癌患者中腹水细胞学检查阳性率为4.8%。2)非子宫内膜样癌(P=0.000)、FIGO分期(2009)为Ⅲ-Ⅳ期(P=0.000)、子宫深肌层受累(P=0.001)、宫颈间质浸润(P=0.018)是子宫内膜癌腹水细胞学阳性的影响因素。3)子宫内膜癌腹水细胞学阳性患者的5年无进展生存率(70.9%vs90.0%)、5年总生存率(72.2%vs 96.0%)均低于腹水细胞学阴性患者;单因素分析腹水细胞学阳性对无进展生存时间和总生存时间的影响,差异均具有统计学意义(P=0.005,P=0.000);4)多因素分析显示腹水细胞学阳性并不是无进展生存时间、总生存时间的独立危险因素(RR=3.812,95%CI 0.897~16.200,P=0.070;RR=3.426,95%CI 0.800~14.673,P=0.097)。结论子宫内膜癌的腹水细胞学阳性与非子宫内膜样的病理类型、FIGO分期(2009)、深肌层浸润、宫颈间质浸润相关。腹水细胞学阳性不是子宫内膜癌的独立预后影响因素。     

The role of peritoneal washings in the diagnosis of endometriosis

Endometriosis, the presence of endometrial tissue outside the uterine corpus, is a common finding in reproductive age women. It is classically diagnosed based on the presence of at least two of the following elements: endometrial glands, endometrial stroma, and hemosiderin‐laden macrophages (HLMs). Although a common finding in surgical pathology specimens at the time of gynecologic surgery, there is little literature on the role of pelvic washings in diagnosing endometriosis. Our study aimed to examine the characteristics of endometriosis in pelvic washings at the time of gynecologic surgery. We report nine cases of endometriosis diagnosed on pelvic washing. Two had a reported history of endometriosis. Four had endometriosis on the concurrent surgical pathology specimen. Liquid‐based cytology was diagnostic of endometriosis in seven patients, including five with glandular cells and HLMs and two with glandular cells, HLMs, and endometrial stromal cells. Cell block was diagnostic of endometriosis in eight patients, including four cases with intact fragments of endometrial glands and stroma. Three cases showed glandular cells and HLMs, while one showed separate fragments of glandular cells and stromal cells. Pelvic washings increased the diagnostic yield for endometriosis at the time of gynecologic surgery, as only four out of nine cases had endometriosis diagnosed on surgical pathology. Cell block in particular aids in the diagnosis, since intact glandular and stromal fragments frequently can be identified.     

Percutaneous image-guided fine-needle aspiration of peritoneal lesions

Fine-needle aspiration (FNA) is a widely accepted technique for the initial tissue diagnosis of a variety of lesions arising within retroperitoneal and intraabdominal viscera. Fear of complications secondary to perforation of the bowel wall has limited the use of FNA in the diagnosis of gastrointestinal and peritoneal masses. A variety of primary and secondary neoplasms involving the peritoneum may present as multiple nodules, as masses, or as diffuse involvement of the peritoneum. When these lesions are associated with mass lesions or areas of significant peritoneal thickening, they become amenable to percutaneous image-guided FNA. We report on our experience with a series of 23 peritoneal lesions investigated by FNA for which subsequent histologic confirmation was available in 19, along with an additional 4 cases without histologic confirmation. One to four passes were made into each lesion, and immediate assessment for adequacy was performed by a cytopathologist in all cases. All 17 cases with a specific cytologic diagnosis and histologic confirmation represented either primary or metastatic neoplasms (5 gastrointestinal stromal tumors, 4 metastatic melanomas, 2 mesotheliomas, 1 lymphoma, 1 example of Kaposi's sarcoma, 1 serous papillary carcinoma of ovarian origin, 1 mucinous adenocarcinoma of ovarian origin, 1 intraabdominal desmoplastic small-cell tumor, and 1 solitary fibrous tumor of the peritoneum). In an additional 4 cases, the aspirates were judged as insufficient for diagnosis, with the smears containing only blood and benign mesothelial cells and/or inflammatory cell elements. These four smears were associated with both neoplastic and nonneoplastic lesions. Surgical confirmation was obtained in only 2 of these cases (1 metastatic melanoma and 1 example of omental and peritoneal involvement by an ovarian adenocarcinoma). Two cases without histologic confirmation were associated with clinically confirmed metastases. In our series, no acute or chronic postprocedural complications were identified, indicating that FNA in this setting is a safe technique. Accurate cytologic diagnosis was achieved in 74% of cases. The overall insufficiency rate was 26%.     

Herpes virus infection in peritoneal fluid: a case report and review of literature

Herpetic infections in body cavity fluids are unusual and are rarely reported in the cytology literature. We report a case of a 74-yr-old woman who developed ascites after undergoing an elective laparoscopic cholecystectomy for biliary colic. Cytology of peritoneal fluid revealed changes in a herpes simplex virus (HSV) infection that was confirmed by immunocytological staining.     

Fallopian tube cytology: A histocorrelative study of 150 washings

The aim of the study was to assess the relationship between fallopian tube lavage cytology and recognized microscopic prognostic features in cancer of the uterine corpus. Tubal (TW) and peritoneal washing cytology (PW), endometrial tumor grade, and tumor involvement of the cervix, myometrium, myometrial vessels, and peritoneum were assessed in 150 patients. Endometrioid adenocarcinoma grade 1 was considered a low-grade tumor, while endometrioid carcinoma grades 2/3, serous/clear cell carcinoma, carcinosarcoma, and high-grade stromal sarcoma were considered high grade. The overall concordance rate for paired TWs and PWs was 72% (108/150). Forward stepwise logistic regression analysis of the 150 tumors revealed that only PWs and cervical involvement were independently predictive of TWs. No relationship was evident between TWs and depth of myometrial invasion, myometrial vascular involvement, or peritoneal metastases. It is concluded that retrograde transtubal spread by malignant endometrial cells occurs independently of myometrial histoprognostic features. TWs provide supporting evidence for diagnostically difficult PWs, and malignant TWs may be detected in the presence of minimally invasive serous/clear cell carcinoma and carcinosarcoma of the endometrium. Diagn. Cytopathol. 16:483–488, 1997. © 1997 Wiley-Liss, Inc.     

Serosal balls detected immunocytochemically in peritoneal lavage obtained during surgery

Using the immunoperoxidase technique, we studied “serosal balls,” which have features resembling those of cells from primary and metastatic tumors, and may thus complicate cytodiagnosis. Serosal balls were detected in 32 (18%) of 174 peritoneal washings. The balls consisted of oval clusters of cells in solid masses surrounded by flattened cells. The interior of the serosal balls was stained green with Papanicolaou method, showing the presence of homogeneous amorphous material, sometimes stained in a filamentous pattern. Almost all serosal balls were stained immunocytochemically for both keratin and vimentin. The interior was stained with antibodies against collagen types I and III. Therefore, these balls were fragments of serous membrane, and contained fibrous tissue and mesothelial cells. © 1995 Wiley-Liss, Inc.     

Pulmonary alveolar proteinosis: a spectrum of cytologic, histochemical, and ultrastructural findings in bronchoalveolar lavage fluid

Pulmonary alveolar proteinosis (PAP) is defined as abundant extracellular proteinaceous periodic acid-Schiff (PAS)-positive material which represents surfactant distending alveolar spaces. While this lesion is defined by histologic findings, there are characteristic radiologic features and cytologic findings in bronchoalveolar lavage (BAL) specimens that together may provide a confident diagnosis. The BAL specimens from all patients for which a diagnosis of PAP was made or suggested on either cytologic or biopsy specimens at University of North Carolina Hospitals from 1990-1999 were reviewed. There were 23 cytologic specimens from 11 patients. Patient ages ranged from 6 wk to 76 yr. All 23 specimens had slides prepared for Papanicolaou stain, 22 specimens (all patients) had Diff-Quik stains, 10 specimens (6 patients) had PAS stains, and 8 specimens (5 patients) had lipid stains. Nine patients had lung biopsies in addition to cytologic specimens. The clinical charts of all patients were reviewed. Twenty-one cytologic specimens were described as cloudy or milky, and 2 were bloody. By chart review and/or biopsy results, 8 patients were felt to have definite PAP. The initial lavage specimens from 6 of these patients showed classic cytologic findings of PAP, consisting of paucicellular specimens dominated by adundant extracellular granular to globular material which was basophilic on Diff-Quik stain, pale to focally eosinophilic on Pap stain, and PAS-positive, diastase-resistant. Five of these patients had biopsies; 3 showed PAP, and 2 were insufficient. Later BAL specimens after therapeutic lavage from these patients were often less characteristic, with scant extracellular material present. The other 2 patients with PAP clinically and by biopsy had atypical cytologic findings, with one showing numerous macrophages with scant PAS-positive material and abundant lipid mimicking lipid pneumonia, and one showing moderate eosinophils in addition to the extracellular proteinacous material. The remaining 3 patients were felt not to have PAP clinically or by biopsy (1 lymphocytic interstitial pneumonitis, 1 rheumatoid lung, and 1 hemosiderosis), and their BAL specimens predominantly contained macrophages with rare proteinaceous extracellular globules. Electron microscopy was performed in 5 patients (4 considered to have PAP, and 1 with lymphocytic interstitial pneumonitis) and in all cases showed whorled myelin figures characteristic of surfactant. The PAP cases and the non-PAP case had identical ultrastructural findings. We conclude that BAL specimens with classic cytologic features and supporting clinical and radiographic evidence may be diagnosed as PAP. Atypical specimens should be approached with caution, and may represent either PAP or other pulmonary diseases with secondary accumulation of surfactant. Cytology specimens taken subsequent to therapeutic lavage from PAP patients may also not be diagnostic.     

Toxoplasmosis in a post-transplant bronchoalveolar lavage: a case report

Toxoplasma gondii usually causes an asymptomatic and then latent infection in human adults; however, a potentially fatal disseminated form can occur in immunocompromised patients. Given that the diagnosis of acute Toxoplasma infection, as opposed to latent disease, relies on finding direct evidence of T. gondii infection in tissue, pathologic examination is critical. There have only been a few reports describing the cytomorphology of Toxoplasma in exfoliative cytology, and no reports of the findings in Thin Prep. In this report, we describe a fatal case of toxoplasmosis in a cardiac transplant patient that was diagnosed by respiratory cytopathology. Although the extracellular organisms were well visualized on the Wright-Giemsa stained cytospin, they were only faintly seen on the Pap-stained cytospin trapped within mucin and were not easily appreciated on the ThinPrep slides nor the H&E stained cell block sections. An immunohistochemical stain for Toxoplasma performed on the cell block was strongly positive, and an autopsy performed on the patient confirmed disseminated infection. Our case illustrates that the diagnosis of Toxoplasma in exfoliative cytology specimens can be challenging since organisms are not well visualized on ThinPrep or Pap-stained material; therefore, Wright-Giemsa stained material can be particularly helpful.     

Metastatic peritoneal mesothelioma in the setting of recurrent ascites: A case report

Malignant peritoneal mesothelioma is uncommon but rapidly fatal with a median survival of less than 1 year. The diagnosis of this entity is often delayed because of the nonspecific presenting symptoms and nonspecific cytological features of the mesothelial cells in the peritoneal fluids. A 72‐year‐old man who had no known history of exposure to asbestos and had longstanding refractory ascites thought to be secondary to alcoholic cirrhosis was found to have widespread metastatic malignant mesothelioma involving the lung, liver, pancreas, peritoneal, and pelvic wall, skin and subcutaneous tissue. Diagn. Cytopathol. 2010;38:675–681. © 2009 Wiley‐Liss, Inc.     

痰液和胸腹水沉积物切片在肿瘤脱落细胞学中的作用

目的　探讨痰和胸腹水沉积物切片在肿瘤细胞学诊断中的意义。方法　对 183例痰液和 2 5 4例胸腹水沉积物进行涂片和石蜡包埋连续切片 ,部分病例做了特染、免疫组化检查。结果　在组织学证实的 96例肺癌中 ,痰液涂片加连续切片的联合检查阳性者 92例 ,阳性率 95 83% ,假阴性 4例。联合检查、切片和涂片三者间差异有显著性 (P <0 0 1)。在组织学证实的 16 2例胸腹腔癌瘤所致的胸腹水沉积物连续切片 ,全部为阳性 ,而在涂片中阳性为 135例 ,两者之间差异有显著性 (P <0 0 1)。结论　痰液和胸腹水沉积物切片避免了单一涂片取材的局限性 ,切片上细胞相对集中 ,易于观察肿瘤的组织形态 ,可增加肿瘤脱落细胞学的诊断价值。     

Diagnosis of peritoneal metastasis in an unruptured hepatocellular carcinoma on ascitic fluid cytology: A rare scenario with brief review of literature

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy in adults occurring in a background of cirrhosis. Peritoneal dissemination of HCC is an unusual presentation with an incidence of 2%–16%. Peritoneal metastasis of an unruptured HCC is extremely uncommon. Despite low yield, ascitic fluid cytology serves as a valuable tool for diagnostic evaluation in a patient of cirrhosis with suspicion of malignant transformation. We present a rare case scenario in an elderly female with cirrhosis where the diagnosis of peritoneal metastasis was established on ascitic fluid cytology and confirmed by immunocytochemistry. This report illustrates the unique clinical presentation of an unruptured HCC with its cytological features and a brief review of literature.     

Cytological findings in a sample of peritoneal aspirate from a case of bile peritonitis

Bile peritonitis (BP) is a rare and serious condition warranting urgent surgical intervention to prevent the high incidence of mortality. BP is ascribed to the leakage of bile into the peritoneal cavity usually due to a perforation of the gallbladder or common bile duct caused by stones or a trauma. The radiological studies are useful in suggesting the diagnosis. The cytological findings of BP have been reported rarely in the literature characterised by the presence of lakes of stringy bile material admixed with variable numbers of histiocytes, mesothelial cells, and some inflammatory cells. Recently, we have examined an aspirate sample of peritoneal fluid (PF) obtained under ultrasound guidance in a case of BP ascribed to the perforation of the gallbladder in a 19-yr-old female patient in which apart from occasional bile pigment-laden macrophages admixed with a few mesothelial cells and inflammatory cells, numerous crystalline structures of varying shapes, sizes, and colour with birefringence along with some microspheroliths were found. At operation, the abdominal cavity showed a large amount of bile and the gallbladder specimen showed two perforations and gangrenous cholecystitis with numerous yellow-brown somewhat friable stones. The foregoing findings in the aspirate appeared to be of interest because to the best of our knowledge, numerous crystalline structures along with the cytological features of BP have not been described in the English literature.     

Cytomorphologic features of well-differentiated papillary mesothelioma in peritoneal effusion: a case report

Well-differentiated papillary mesothelioma (WDPM), a distinct subtype of diffuse malignant mesothelioma, usually occurs in the peritoneum and is seen most commonly in women of reproductive age. Histologic features of WDPM include papillary growth and stout fibrous cores surrounded by a single layer of tumor cells. We present the case of a 73-year-old woman without subjective symptoms who showed signs of peritoneal effusion during a routine examination and for whom cytologic examination of the ascitic fluid was performed. Many spherical clusters, with a smooth external surface composed of a single layer of uniform cuboidal cells, were observed. Within each cluster, a collagenous ball showed light green Papanicolaou staining. Immunohistochemistry of surgical specimens showed tumor cells positive for calretinin, D(2)-40, and HBME-1 staining. The histologic diagnosis was WDPM. The identification of a collagenous ball within these clusters is a useful cytologic finding for the diagnosis of WDPM. WDPM should be suspected when numerous collagenous balls are present by effusion cytology and isolated cells are not.     

Diagnostic value of bronchoalveolar lavage and bronchial washing in sputum-scarce or smear-negative cases with suspected pulmonary tuberculosis: a randomized study

ObjectivesBronchoalveolar lavage (BAL) and bronchial washing (BW) are two major methods used to obtain high-quality respiratory specimens from patients with suspected pulmonary tuberculosis (TB) but a sputum-scarce or smear-negative status. We aimed to compare the value of BAL and BW in the diagnosis of TB in such patients.MethodsWe enrolled patients with suspected pulmonary TB but with a sputum-scarce or smear-negative status who were referred for bronchoscopy between October 2013 and January 2016. Participants were randomized into the BAL and BW groups for evaluation. The primary outcome was the diagnostic yield for TB detection. Secondary outcomes included culture positivity, positivity of nucleic acid amplification tests (NAATs) for Mycobacterium tuberculosis and procedure-related complications.ResultsA total of 94 patients were assessed and 91 (43 in the BAL group, 48 in the BW group) were analysed. Twenty-one patients (48.8%) in the BAL group and 30 (62.5%) in the BW group had a final diagnosis of pulmonary TB. The detection rate of M. tuberculosis by culture or NAAT was significantly higher in BAL specimens than in BW specimens (85.7% vs 50.0%, p 0.009). The procedure-related complications were hypoxic events, 2/43 (4.7%) in the BAL group and 5/48 (10.4%) in the BW group; and post-bronchoscopic fever, 3/43 (7.0%) in the BAL group and 4/48 (8.3%) in the BW group.DiscussionAs long as it is tolerable, BAL rather than BW, should be used to obtain specimens for the diagnosis of pulmonary TB in sputum-scarce or smear-negative cases.