Intracytoplasmic lumina in invasive micropapillary carcinoma of the lung

Micropapillary carcinoma of the lung is a rare neoplasm, and several reports on micropapillary carcinoma of the lung have been presented to date. We present a case of micropapillary carcinoma of the lung here. A 75-yr-old Japanese man received the medical checkup and his chest X-ray disclosed the abnormal shadow of the lower lobe of the left lung. The histological examination of resected lung and extirpated lymph node showed the finding of micropapillary carcinoma. Some neoplastic cells of primary site contained intracytoplasmic lumina positive for Alcian blue and PAS stains. Pleural effusion appeared 9-mo after the operation. The cytology of pleural effusion showed cohesive clusters of neoplastic cells consisting of 3-20 cells without fibrovascular core. Additionally, intracytoplasmic lumina were observed in some neoplastic cells. Finally, carcinoma cells with micropapillary morphology may possess the intracytoplasmic lumina in the cytoplasm of metastatic site as well as primary site.     

Lung adenocarcinoma with a micropapillary pattern: a clinicopathological study of 25 cases

Lung adenocarcinoma with a micropapillary pattern has recently been described, but its biological behavior is as yet uncertain. In this article we present a clinicopathological study of lung adenocarcinoma with micropapillary morphology. We selected 25 patients with lung adenocarcinoma with micropapillary morphology from the 2001-2004 pathology files (age range 54 to 81 years; mean 64.5 years). Micropapillary carcinoma is predominantly located at the periphery of the tumor nodule or mass and occurs irrespective of the subtype of the adenocarcinoma. A micropapillary component was seen against a mucinous background in three cases and microcalcifications resembling psammoma bodies were seen in one case. Four cases showed intensive invasive growth such as micropapillary adenocarcinoma of the breast and 21 showed alveolar type morphology with piling-up of the neoplastic cells with or without stromal invasion. Seven of twenty-three (30.4%) showed lymph node metastases at time of operation. Twelve of twenty-five (48%) showed pleural invasion. Regarding clinical outcome, 14 patients were alive without disease, 5 were alive with disease, and 5 died of the lung adenocarcinoma. No significant relationship was found between the extent of the micropapillary component and prognosis. However, the carcinoma seen in the five patients who died showed breast type histology with intensive invasive growth in three cases and alveolar type histology with intensive stromal invasion in two. Lung micropapillary carcinoma of breast type may behave more aggressively than the alveolar type.     

The value of ThinPrep and cytospin preparation in pleural effusion cytological diagnosis of mesothelioma and adenocarcinoma

The diagnosis of malignant mesothelioma requires an integration of the clinical presentation, radiological studies, and immunohistochemical stain of histological sections. Cytological diagnosis on pleural effusions of mesothelioma and pulmonary adenocarcinoma is highly desirable but debatable. A spectrum of cytological features has been found to be associated more commonly with malignant mesothelioma (e.g., peripheral cytoplasmic skirt, bubbly cytoplasm, cyanophilic cytoplasm, and scalloped border of cell balls) vs. adenocarcinoma (e.g., two-cell population, inspissated cytoplasmic material, cytoplasmic vacuole, angulated and indented nuclei, and smooth border of cell balls) to only name a few. The current study is designed to assess whether the introduction of a liquid-based technology such as ThinPrep (TP) can provide additional diagnostic value in addition to the conventional cytospin Diff-Quik (DQ) preparations. Pleural effusion specimens were prepared with split samples for DQ-stained cytospin and Papanicolaou-stained liquid-based TP. Fifteen pleural effusion samples with immunohistologically confirmed malignant mesothelioma and 13 pleural effusion samples of immunohistologically confirmed pulmonary adenocarcinomas were retrieved from our files. Both DQ cytospin- and Papanicolaou-stained TP slides were evaluated for the known cytological features associated with malignant mesothelioma (25 cytological features) and adenocarcinoma (22 cytological features) without knowledge of the original cytological and histological diagnoses. The McNemar test was used to compare these two cytological preparations for both malignant mesothelioma and pulmonary adenocarcinoma. In the malignant mesothelioma group, 4 of 25 cytological features evaluated, bubbly cytoplasm (P = 0.002), vacuolated cytoplasm (P = 0.005), cell-in-cell arrangement (P = 0.007) and irregular nuclear contour (P = 0.083), were seen more frequently in the DQ cytospin preparation, as opposed to only one feature, nuclear size enlargement (P = 0.008), more readily seen using TP. In the pulmonary adenocarcinoma group, only 1 of 22 cytological features evaluated, presence of angulated or indented nuclei (P = 0.025), was seen more frequently in DQ as opposed to two features, presence of two- cell population (P = 0.04) and presence of micropapillary structures (P = 0.1), were seen more readily in TP. All other cytological features evaluated distinguishing mesotheliomas (20 features) and pleural adenocarcinomas (19 features) were seen equally readily in both types of specimen preparation techniques. This study suggests that the liquid-based TP preparation of pleural effusions does not appear to provide additional diagnostic value when compared with the DQ cytospin preparation in the cytological distinction between mesothelioma and adenocarcinoma in pleural effusions. Most cytological features evaluated, 20 of 25 (mesothelioma) and 19 of 22 (adenocarcinoma), can be seen in both preparation techniques.     

Adenocarcinoma cells in effusion cytology as a diagnostic pitfall with potential impact on clinical management: A case report with brief review of immunomarkers

Distinguishing metastatic carcinoma cells from reactive mesothelial cells in effusion samples is often challenging based on morphology alone. Metastatic carcinoma cells in fluid samples may mimic reactive mesothelial cells due to overlapping cytological features. We report a case of a pleural effusion in a 51‐year‐old female patient with a medical history significant for bilateral ovarian tumors and peritoneal implants diagnosed as serous tumor of borderline malignant potential. The effusion was composed almost entirely of adenocarcinoma cells that morphologically mimicked reactive mesothelial cells. The diagnosis of metastatic adenocarcinoma was made after a wide immunostaining panel of antibodies. Recognizing metastatic adenocarcinoma cells in effusion samples can be challenging and an accurate diagnosis may have significant impact on clinical management as demonstrated by this case. Diagn. Cytopathol. 2012;42:253–258. © 2012 Wiley Periodicals, Inc.     

Micropapillary variant of transitional cell carcinoma of the ureter

Micropapillary variant of transitional cell carcinoma (TCC) is a rare entity, having a distinct micropapillary component mimicking papillary serous carcinoma of the ovary and has been reported exclusively in the urinary bladder. We experienced a case of micropapillary variant of TCC in the ureter. The tumor showed a predominant proportion of micropapillary component and accompanied a TCC in situ lesion and a high-grade TCC. A metastatic lesion in the regional lymph node also showed an entirely micropapillary pattern. Initially, our case was confused with adenocarcinoma, especially metastatic, because the micropapillary architecture resembled an abortive glandular structure and tumor cell nests were predominantly located in empty spaces mimicking vascular invasion. The patient died with peritoneal metastases 20 months after the initial diagnosis. We report the first case of a micropapillary variant of TCC occurring in the ureter.     

Pleomorphic ductal carcinoma of the breast with predominant micropapillary features

An 83-year-old woman with long-standing chronic ischemic cardiac and obstructive pulmonary disease, presented with a painless tumor in her right breast. Microscopically the tumor consisted of micropapillary formations and loosely cohesive nests and strands of large, highly pleomorphic cells. Micropapillary formations were surrounded by peritumoral retraction clefting, and the papillae lacked a true fibrovascular core. Multinucleated giant and bizarre tumor cells were also present and numerous. Within the tumor a high-grade intraductal component with the same cell morphology and necrosis and mucin production was found. Micropapillary pattern occupied approximately 60% of the tumor mass, loosely cohesive nests and strands approximately 20% and an intraductal component was noted in approximately 20% of the tumor mass. On immunohistochemistry the tumor cells were positive for pan-cytokeratin, epithelial membrane antigen (EMA), S100 protein and E-cadherin while estrogen and progesterone receptors, HER2-neu and Bcl2 were negative. EMA staining was diffuse and observed in the outer and inner margins of neoplastic nests. The diagnosis of pleomorphic breast carcinoma with predominant micropapillary features was established. In summary, micropapillary carcinoma can be distinguished from other types of breast carcinoma with micropapillary growth pattern on the basis of reverse cell polarity, which is easily confirmed on immunohistochemistry.     

Cytodiagnostic aspects of lung adenocarcinoma manifesting with micropapillary pattern in sputum

The micropapillary pattern of lung adenocarcinoma was discussed in the 2004 World Health Organization classification and is now proposed as a distinct pattern in the new International Multidisciplinary Classification of Lung Adenocarcinoma Guidelines. The micropapillary pattern is histologically characterized by papillary tufts lacking a central fibrovascular core and is associated with an unfavorable prognosis. Herein, we report the cytological features of lung adenocarcinoma with the micropapillary pattern in a sputum specimen. A 75‐year‐old woman presented with a productive cough, blood‐tinged sputum, and some symptoms of upper respiratory tract infection. The initial impressions from her chest radiograph and computed tomography scan indicated pneumonia. However, the initial sputum cytology sample showed a few clusters of cells with abnormal three‐dimensional structure, interpreted as adenocarcinoma. These cells were small and had minimal cytologic atypia, demonstrating a potential diagnostic pitfall. The following biopsy confirmed lung adenocarcinoma with the micropapillary pattern. Here, we describe this case and discuss the differential diagnosis of pulmonary entities exhibiting similar morphologies. Diagn. Cytopathol. 2014;42:902–905. © 2014 Wiley Periodicals, Inc.     

Cardiac tamponade as an initial presentation of papillary carcinoma with psammoma bodies and intranuclear grooves—A diagnostic dilemma

Involvement of body fluids by adenocarcinoma is a common phenomenon. However, metastasis to the pericardial fluid by adenocarcinoma is a rare occurrence. The most common malignancies associated with malignant pericardial effusion are carcinoma of the lung, breast, esophagus, melanoma, lymphoma, and leukemia. Here, we discuss a case of a 36‐year‐old female with hemorrhagic pericardial effusion presenting with cardiac tamponade and psammoma bodies which was suspected and reported as metastatic papillary carcinoma of thyroid on cytomorphology; however, the immunocytochemical and radiological features confirmed metastatic papillary adenocarcinoma of lung contrary to the thyroid which is more common and expected.     

Cytologic diagnosis of pulmonary adenocarcinoma with micropapillary pattern: Does it correlate with the histologic findings?

Micropapillary adenocarcinoma is associated with poor‐prognosis in several organs including the lung. The presence of small tight balls of neoplastic cells devoid of fibrovascular core in cytological preparations (micropapillary tufts) has been described as characteristic of micropapillary adenocarcinoma. In the lung, however, this criterion has not been validated. The cytological material of 46 cases of histologically proven pulmonary adenocarcinoma with a micropapillary component was compared to 33 cases with no micropapillary component to determine the specificity of micropapillary tufts for the histologic diagnosis of micropapillary adenocarcinoma. Other histologic patterns of invasive pulmonary adenocarcinomas (acinar, papillary, and solid) were also compared with patterns of neoplastic cell aggregates in cytological preparations. There were no significant differences in the distribution of micropapillary clusters between the two groups. The positive predictive value for the cytologic diagnosis of a micropapillary component in lung adenocarcinomas was of 64%. Similar findings were observed for other invasive patterns. Therefore, the detection of micropapillary tufts in cytology is not specific for the diagnosis of a pulmonary micropapillary adenocarcinoma in the lung. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

PSEUDOMESOTHELIOMATOUS CARCINOMA OF THE LUNG WITH HISTOCHEMICAL AND IMMUNOHISTOCHEMICAL STUDY

An autopsy case of pseudomesotheliomatous carcinoma of the right lung in a 56–year–old man occupationally exposed to stone dust is presented. From open biopsy specimens in which polyhedral epithelium–like cells appeared arranged in nests, sheets, and trabecula without apparent tubular pattern, a malignant pleural mesothelioma was suspected. At autopsy, the right pleural cavity was obliterated by the tumor mass which covered the collapsed pulmonary parenchyma and was clearly demarcated from it. The gross appearance of the tumor was similar to that of malignant pleural mesothelioma. Histologically, marked Interstitial fibrosis of the subpleural parenchyma of both lungs was observed, and the tumor tissue was interspersed in the parenchyma adjacent to the tumor mass. The tumor showed both intracytoplasmic and intercellular positive materials with colloidal iron, alcian blue (pH 2.5), and toluidine blue stains, which entirelly disappeared after streptomyces hyaluronidase digestion. A small amount of intracytoplasmic PAS–positive material resistent to diastase digestion was also observed. Immunohlstochemical staining for carcinoembryonic antigen, which is said to be negative in malignant pleural mesothelioma, was positive intracellularly. There were no histologic findings indicating asbestos exposure. From these findings, the authors made a diagnosis of poorly differentiated adenocarcinoma, which was characterized by the production of hyaluronic acid. ACTA PATHOL. JPN. 33: 415–423, 1983.     

Desmoplastic small round cell tumor with sphere‐like clusters mimicking adenocarcinoma

Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive neoplasm that predominantly affects young men. DSRCT often presents as multiple nodules on the serosal surface and is histologically categorized as a small round cell tumor. However, the cytological spectrum of DSRCT is not fully understood because of its rarity. Here, we report an unusual case of DSRCT that showed spheres of cells without stromal cores in pleural fluid cytology material, a finding that is typically associated with metastatic adenocarcinoma and mesothelioma. The specimen from a simultaneous needle biopsy showed the classic histology of DSRCT, comprising nests of small round cells set in desmoplasia. The diagnosis of DSRCT was further supported by immunohistochemical coexpression of cytokeratin and desmin, as well as Ewing sarcoma breakpoint region 1 gene rearrangement, which was determined by fluorescence in situ hybridization. The unusual cytological finding in this case illustrates a potential pitfall of the cytological diagnosis of pleural fluid or ascites. DSRCT should not be excluded from the differential diagnosis when sphere‐like round cell clusters are observed in pleural or abdominal effusion, particularly in young male patients. Diagn. Cytopathol. 2015;43:214–217. © 2014 Wiley Periodicals, Inc.     

HER2/HER3‐positive metastatic salivary duct carcinoma in the pleural effusion: A case report

Salivary duct carcinoma (SDC) is an aggressive form of salivary gland tumor, and SDC patients tend to be older men, more commonly in advanced stage with a poorer prognosis. Although the cytological characteristics of SDC on fine‐needle aspiration cytology have been well‐described at the primary site, they have not been explored in metastasis. Here we reported a case of HER2/HER3‐positive metastatic SDC in the lung and pleural effusion. The patient was a man in his 50s who had undergone extended total parotidectomy in 2008. He was originally diagnosed as having HER2‐positive left parotid SDC. Six years later a mass was discovered in the left lung by chest computed tomography (CT) and was diagnosed as metastatic SDC by both bronchial biopsy and cytology. Subsequently he had a recurrent SDC in the left pleural effusion and died of respiratory failure. Cytological findings from bronchial brushing smear showed small sheet clusters in a slightly necrotic background. In the pleural effusion cytology, tumor cells appeared as ball‐like clusters of epithelioid cells with apocrine‐like findings. In immunocytochemistry, HER3 of SDC cells in pleural effusion was significantly overexpressed relative to the matched primary tumor, even though HER2 amplification did not change. Cytological findings and HER family receptors differed between the primary and metastatic SDC. Therefore, molecular tests, such as protein expression and gene amplification using cytological specimens, may become important in future when determining therapy strategies in patients with distant metastasis.     

Pleural metastasis from parotid secretory carcinoma: First report of morphology on effusion cytology,and role of pan-TRK immunohistochemistry

Distant metastasis from salivary gland secretory carcinoma (SC) is rare, with lung and pleura being the most frequent site. While cytological features of SC on fine needle aspirates are well documented, its morphology in serous effusions has not been described. We describe the cytomorphological features on effusion cytology of two patients with ETV6::NTRK3 fusion-positive SC, who subsequently developed pleural metastases. Cytospin preparations of pleural fluid showed tightly cohesive, irregularly shaped and ball-like clusters of large tumor cells with scant to abundant uni- and multi-vacuolated cytoplasm. Nuclei were eccentrically placed, round to oval, vesicular, with finely granular chromatin, irregular nuclear membranes and conspicuous to prominent nucleoli. With these features, the tumors resembled an adenocarcinoma, indistinguishable from a lung primary. Cell blocks from both cases showed tumor fragments, some of which had the hollow appearance of transversely sectioned cell spheres as seen in lung and breast adenocarcinomas. Immunohistochemistry on cell blocks revealed nuclear pan-TRK positivity in both cases. Case 1 also showed focal mammaglobin staining, and TTF1 negativity. Pleural metastases from SC may mimic other adenocarcinomas. As targeted therapy, that is, selective TRK inhibitors are available for treatment of metastatic disease, NTRK3 fusion status is not only diagnostic, but also required to plan treatment. Pan-TRK immunohistochemistry serves as a viable cost-effective, easy to apply surrogate marker for NTRK3 fusion, particularly in diagnostic laboratories lacking easy access to molecular testing on cytological material.     

Micropapillary adenocarcinoma of lung: Morphological criteria and diagnostic reproducibility among pulmonary pathologists

ContextInvasive micropapillary adenocarcinoma (MPC) is an aggressive variant of lung adenocarcinoma, frequently manifesting with advanced stage lymph node metastasis and decreased survival.ObjectiveIdentification of this morphology is important, as it is strongly correlated with poor prognosis regardless of the amount of MPC component. To date, no study has investigated the morphological criteria used to objectively diagnose it.DesignHerein, we selected 30 cases of potential MPC of lung, and distributed 2 digital images per case among 15 pulmonary pathology experts. Reviewers were requested to diagnostically interpret, assign the percentage of MPC component, and record the morphological features they identified. The noted features included: columnar cells, elongated slender cell nests, extensive stromal retraction, lumen formation with internal epithelial tufting, epithelial signet ring-like forms, intracytoplasmic vacuolization, multiple nests in the same alveolar space, back-to-back lacunar spaces, epithelial nest anastomosis, marked pleomorphism, peripherally oriented nuclei, randomly distributed nuclei, small/medium/large tumor nest size, fibrovascular cores, and spread through air-spaces (STAS).ResultsCluster analysis revealed three subgroups with the following diagnoses: “MPC”, “combined papillary and MPC”, and “others”. The subgroups correlated with the reported median percentage of MPC. Intracytoplasmic vacuolization, epithelial nest anastomosis/confluence, multiple nests in the same alveolar space, and small/medium tumor nest size were the most common criteria identified in the cases diagnosed as MPC. Peripherally oriented nuclei and epithelial signet ring-like forms were frequently identified in both the “MPC” and “combined papillary and MPC” groups.ConclusionsOur study provides objective diagnostic criteria to diagnose MPC of lung.     

Diagnostic efficacy of electron microscopy and pleural effusion cytology for the distinction of pleural mesothelioma and lung adenocarcinoma

The diagnosis of malignant pleural mesothelioma (MPM) is challenging and requires immunohistochemistry or electron microscopy assays to specifically differentiate MPM from lung adenocarcinoma. An ultrastructural study of fresh tissue is considered to be the “gold standard.” In most cases, the first diagnostic approach is performed on pleural effusion, and in some patients, this is the only available sample for diagnosis. The aim of the present study is to evaluate if an examination of pleural effusion samples based on electron microscopy (EMpe) is a useful tool for the differential diagnosis of MPM and lung adenocarcinoma. An EMpe study was performed in 25 pleural effusion samples. Histological and immunohistochemical markers confirmed the diagnosis of either mesothelioma (5) or adenocarcinoma (20). Of the five cases that were diagnosed with mesothelioma, two samples (40%) showed cells with “bushy” microvilli, which are characteristic of mesothelioma, by EMpe, and three were acellular (60%). Of the 20 cases of adenocarcinoma, EMpe showed cells with short microvilli in 9 (45%), and 11 were acellular (55%). EMpe identifies unequivocal morphological changes that are useful for the differential diagnosis of MPM or adenocarcinoma when the pleural effusion sample contains evaluable tumor cells.     

Pleural malignant mesothelioma with invasive micropapillary component and its association with pulmonary metastasis

The micropapillary pattern (characterized by papillary structure with tufts lacking a central fibrovascular core) is a predictor of aggressive carcinoma. The purpose of the present study was to review 34 pleural malignant mesotheliomas (21 epithelioid, five sarcomatoid, seven biphasic and one lymphohistiocytoid), with special reference to the presence of invasive micropapillary component. Two invasive micropapillary pattern‐positive tumors were identified. The invasive micropapillary pattern was seen to have a focal distribution in 15–20% of the tumor tissues. The majority of the invasive micropapillary clusters expressed MUC1 along the outer cell surface. Analysis of pleural malignant mesotheliomas with epithelioid features and with or without invasive micropapillary pattern (21 epithelioid and seven biphasic subtypes) indicated pulmonary micrometastases in only the invasive micropapillary‐positive tumors (P < 0.015), and the spread was probably via the lymphatics. Lymphatic involvement (confirmed on immunohistochemistry with D2‐40 antibody) and lymph node metastasis were found in both of the invasive micropapillary‐positive tumor patients, whereas they were noted in only one of 10 (10%, P < 0.046) and three of nine (30%) invasive micropapillary‐negative patients. To the authors’ knowledge this is the first study to indicate the presence of invasive micropapillary component in pleural malignant mesothelioma. This component can predict more aggressive lymphatic spread, similar to that of carcinomas in other organs with micropapillary pattern.