WT1, monoclonal CEA, TTF1, and CA125 antibodies in the differential diagnosis of lung, breast, and ovarian adenocarcinomas in serous effusions

The distinction between metastatic adenocarcinomas of lung (LAC), breast (BAC), and ovary (OAC) in serous effusions can be very difficult since they all can present as tight cell clusters. This is particularly challenging when the malignant effusion is the patient's initial presentation or when the patient has a history of more than one primary. The aim of this study is to evaluate the usefulness of WT1, monoclonal CEA (mCEA), TTF1, and CA125 antibodies in the differential diagnosis of metastatic adenocarcinoma from the lung, breast and ovary in serous effusions. Forty-six samples of serous effusions with their corresponding cell blocks were retrieved from our hospital computer system, including 13 BACs, 13 LACs, and 20 OACs. The diagnoses were confirmed by the surgical resection. Formalin-fixed and paraffin-embedded cell block sections were immunostained for WT1, mCEA, TTF1, and CA125. Two observers blindly reviewed the immunostained slides without knowledge of the previous clinical or histologic diagnoses. The staining intensity was graded semiquantitatively as negative, 0; weak, 1+; moderate, 2+; and strong, 3+. The percentage of positively staining cells was estimated. The distribution patterns of reactivity for WT1 and TTF1 were recorded as nuclear, and mCEA and CA125 as membranous stain. Metastatic OACs showed positive immunoreactivity to WT1 in 19/20 (95%) cases, CA125 in 20/20 (100%), and all showed negative reaction for both mCEA (0/20, 0%) and TTF1 (0/20, 0%). BAC showed positive reaction in 6/13 (46%) cases to CA125 and mCEA. Staining pattern was diffuse for CA125 and focal for mCEA. Only 2/13 (15%) were positive for WT1, while all of 13 BAC cases (0/13, 0%) were negative for TTF1. LAC showed positive immunoreactivity for TTF1 in 9/13 (69%) with a characteristic nuclear staining pattern, but only 3/13 (23%) were focally stained for WT1. In addition, 8/13 (62%) of LAC cases were positive for both CA125 and mCEA. Our results demonstrate that the WT1 stain is specific for metastatic carcinoma of ovarian primary, showing a high sensitivity. In addition, CA125 stain is very sensitive for OACs, but could be positive in about a half of LAC and BAC cases. An immunostaining pattern of positive mCEA as well as negative WT1 rules out OACs, raising the possibility of LACs and BACs. A positive TTF1 staining supports the diagnosis of metastatic carcinoma originating from lung rather than breast, while a negative TTF1 favors the diagnosis of a breast primary. Immunohistochemical studies with WT1, TTF1, and mCEA antibodies are useful in the differential diagnosis of metastatic adenocarcinomas of lung, breast, and ovary. Diagn. Cytopathol. 2007;35:370–375. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56105/1/20643_ftp.pd

Deciduoid mesothelioma: Cytologic presentation and diagnostic pitfalls

We report two cases of malignant deciduoid mesothelioma (MDM), a very rare variant of malignant mesothelioma (MM). Case 1: An 18‐year‐old male with no history of asbestos exposure presented with worsening abdominal pain, anorexia, and vomiting after a motor vehicle accident. A CT scan showed small amount of ascites and abdominal mass. An exploratory laparotomy revealed multiple yellow tan, firm nodules on the peritoneum and omentum. He received palliative treatment and died 5 months after the diagnosis. Case 2: A 64‐year‐old female with history of asbestos exposure initially presented with abdominal distension. CT scan showed abdominal mass with a large amount of ascites. A diagnostic laparoscopy revealed multiple peritoneal nodules. She underwent several regimens of chemotherapy over a period of 69 months and is still alive to date. In both cases, features of mesothelial origin were subtle and the smears showed predominantly single cells with marked nuclear atypia. The second case also contained few two‐dimensional loose cell clusters with scalloped or hobnail borders. The clusters often exhibited a pseudoacinar structure surrounding a globular extracellular material. Groups of three to four cells often formed doublets and triplets with cell‐to‐cell windows. Our results show that MDM may not present with the traditional cytological features described in MM and can manifest with more nuclear pleomorphism resulting in erroneous diagnosis. Recognition of the subtle mesothelial features along with the appropriate ancillary tests is essential for accurate diagnosis. Diagn. Cytopathol. 2013. © 2012 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98759/1/22902_ftp.pd

Growth and form of the mound in Gale Crater, Mars: Slope wind enhanced erosion and transport

Ancient sediments provide archives of climate and habitability on Mars. Gale Crater, the landing site for the Mars Science Laboratory (MSL), hosts a 5-km-high sedimentary mound (Mount Sharp/Aeolis Mons). Hypotheses for mound formation include evaporitic, lacustrine, fluviodeltaic, and aeolian processes, but the origin and original extent of Gale’s mound is unknown. Here we show new measurements of sedimentary strata within the mound that indicate ∼3° outward dips oriented radially away from the mound center, inconsistent with the first three hypotheses. Moreover, although mounds are widely considered to be erosional remnants of a once crater-filling unit, we find that the Gale mound’s current form is close to its maximal extent. Instead we propose that the mound’s structure, stratigraphy, and current shape can be explained by growth in place near the center of the crater mediated by wind-topography feedbacks. Our model shows how sediment can initially accrete near the crater center far from crater-wall katabatic winds, until the increasing relief of the resulting mound generates mound-flank slope winds strong enough to erode the mound. The slope wind enhanced erosion and transport (SWEET) hypothesis indicates mound formation dominantly by aeolian deposition with limited organic carbon preservation potential, and a relatively limited role for lacustrine and fluvial activity. Morphodynamic feedbacks between wind and topography are widely applicable to a range of sedimentary and ice mounds across the Martian surface, and possibly other planets

Fine‐needle aspiration of gray zone lesions of the breast: Fibroadenoma versus ductal carcinoma

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99655/1/dc22914.pd

The use of immunocytochemical study in the cytologic diagnosis of melanoma: Evaluation of three antibodies

There are limited studies on the utility of immunostaining in cytologic specimens suspected of melanoma. In this study, we examined the performance of the most commonly used antibodies including monoclonal antibodies against Melan‐A (A103), S‐100, and HMB‐45 antigens. Immunostains were performed on formalin‐fixed, paraffin‐embedded cell blocks prepared from 100 cytologic specimens. The specimens consisted of 57 melanomas and 43 nonmelanocytic neoplasms. Of 57 melanomas, 53 showed positive reaction to Melan‐A antibody while 51 and 41 revealed positive immunostaining for S‐100 and HMB‐45, respectively. Of 43 nonmelanocytic neoplasms, 10, 4, and 8 specimens stained positive with an antibody against S‐100, HMB‐45, and Melan‐A, respectively. However, the false‐positive immunostaining for Melan‐A was eliminated in seven of the eight specimens after applying the pretreatment with avidin/biotin blocking reagents. Overall, the highest sensitivity and negative predictive value (NPV) were achieved in Melan‐A antibody (93 and 90%) compared with antibodies to S‐100 (89 and 85%), and HMB‐45 (72 and 71%). Initially, an intermediate specificity and positive predictive value (PPV) were obtained for Melan‐A antibody (81 and 87%) that were greater than S‐100 (77 and 84%), and lower than HMB‐45 (91 and 91%). However, the aforementioned treatment with avidin/biotin blocking reagents improved both specificity (98%) and PPV (98%) for Melan‐A antibody. In conclusion, by blocking endogenous biotin, Melan‐A antibody offers the greatest performance. In terms of cost‐effectiveness, we suggested that Melan‐A antibody should be used as the first‐line antibody for detecting melanoma in the cytologic specimens. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96298/1/21791_ftp.pd

A metastatic renal carcinoid tumor presenting as breast mass: A diagnostic dilemma

We present clinicopathological and cytological findings of a well-defined breast mass in a patient with history of primary renal carcinoid tumor. Fine-needle aspiration (FNA) cytology showed monotonous tumor cells with plasmacytoid appearance arranged singly and in small clusters. Occasional tumor cells were arranged in acinar architecture resembling glandular differentiation. Tumor cells showed fine speckled chromatin. The unusual location for metastasis of this rare type of carcinoid tumor and overlapping cytological features with primary mammary carcinoma led to an erroneous preliminary cytological diagnosis of primary breast carcinoma with plasmacytoid features. Tumor cells in the corresponding cell block showed strong diffuse positivity for synapthophysin and pan-cytokeratin with weak focal positivity for chromogranin markers. These patterns of immunostaining were similar to the original renal carcinoid tumor. To the best of our knowledge, a few cases of carcinoid tumor metastatic to the breast have been reported in the literature and more than half of these cases were initially misdiagnosed as primary breast carcinoma causing unnecessary surgical treatment. This is a first reported case of metastatic renal carcinoid tumor into breast diagnosed with FNA biopsy. This report highlights the cytological features of well-differentiated neuroendocrine tumor (carcinoid tumor) and its potential diagnostic pitfalls. Diagn. Cytopathol. 2007;35:306–310. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56036/1/20631_ftp.pd

Cytomorphologic features of metastatic urothelial carcinoma in serous effusions

Metastatic urothelial carcinoma (UC) to serous effusion (SE) is extremely rare and its cytomorphological features have only been described in case reports. In this study, we searched the pathology database at University of Michigan for SEs due to metastatic UC in the last 20 years. A total of 25 cases from 20 patients with clinically and pathologically confirmed metastatic UC in SEs were retrieved. The specimens consisted of 15 pleural, 8 peritoneal, and 2 pericardial effusions. Smears were reviewed and evaluated for the following features: cellularity, single cells, cell clusters or short cords, cell wrapping, “windows” between the cells, two‐tone cytoplasm, cytoplasmic vacuoles, signet ring cells, nuclear to cytoplasmic (N/C) ratio, nuclear hyperchromasia, irregular nuclear membrane, nuclear centricity, double or multiple nuclei, nucleoli, anaplastic cells and mitosis. Our results showed that UC manifested in SEs predominantly as a single cell population with or without clusters or short cords, and frequently exhibited the “cell wrapping” of two or more cells. Individual UC cell in SEs exhibited nuclear enlargement with increased N/C ratio, irregular nuclear membranes, hyperchromatic coarse chromatin and frequently prominent nucleoli. Double or multinucleated cells, cells with vacuolated cytoplasm or signet ring appearance were also frequently present. Our results demonstrated that while certain features could suggest the diagnosis of UC, the cytomorphological features are not specific and often overlap with those of reactive mesothelium, mesothelioma, metastatic adenocarcinoma, or squamous cell carcinoma in SEs. Accurate diagnosis of UC rests on the combination of clinical history, cytomorphologic features and appropriate immunohistochemical panel. Diagn. Cytopathol. 2013. © 2012 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98804/1/22896_ftp.pd

Fine needle aspiration of primary mediastinal synovial sarcoma: Cytomorphologic, immunohistochemical, and molecular study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102691/1/dc22912.pd

Minimizing the diagnosis of “follicular lesion of undetermined significance” and identifying predictive features for neoplasia

We used proposed standard morphologic criteria as a guideline to conduct a 10‐year retrospective review of thyroid fine‐needle aspiration specimens that were originally interpreted as “follicular lesion of undetermined significance” and followed by surgical intervention. We sought to investigate whether the indeterminate diagnosis could be minimized by assessing various cytomorphologic features and identifying the features predictive of neoplasia. Using the standard morphologic criteria, we semi‐quantitatively assessed a total of 24 cytomorphologic features in 123 aspirates and recorded an overall interpretation on completion of the review. Cyto‐histologic correlation was evaluated and logistic regression model was performed to identify cytomorphologic features predictive of neoplasia. Although 32 of 123 aspirates remained in the indeterminate category, the retrospective review reclassified 64 aspirates as non‐neoplasia and 27 aspirates as neoplasia. Histologic confirmation was achieved in 47 (73.4%) non‐neoplastic and 15 (55.6%) neoplastic aspirates with a diagnostic accuracy of 68.1%. Furthermore, our analysis demonstrated that neoplasia is positively associated with the presence of syncytial tissue fragments, isolated microfollicles, follicles with scalloped borders, scant cytoplasm, irregular nuclear membranes, nuclear overlapping, coarse chromatin, and increased cellularity. On the contrary, the presence of honeycombing tissue fragments, background colloid, and histiocytes inversely correlated with neoplasia. Overall, using proposed standard morphological criteria can minimize the diagnosis of “follicular lesion of undetermined significance,” and allow for more accurate cyto‐histologic correlation, and thereby playing a substantial role in reducing unnecessary surgical intervention. Diagn. Cytopathol. 2010. © 2010 Wiley‐Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87071/1/21459_ftp.pd