Acinar cell cystadenoma: A challenging cytology diagnosis,facilitated by moray® micro‐forceps biopsy

Acinar cell cystadenoma is a rare, benign cystic lesion of the pancreas. There have been only a few retrospective reports on its cytological features. We present the first case of acinar cell cystadenoma in a 65‐year‐old woman, diagnosed pre‐operatively by pancreatic cyst fluid cytology and Moray^® micro‐forceps biopsy. We emphasize possible diagnostic pitfalls of acinar cell cystadenoma cyst fluid cytology and suggest useful morphologic, immunohistochemical, and other clues to aid in diagnosis. Diagn. Cytopathol. 2017;45:557–560. © 2017 Wiley Periodicals, Inc.     

Foamy gland pancreatic ductal adenocarcinoma diagnosed on EUS‐FNA: A histochemical,immunohistochemical, and molecular report

The foamy gland pattern (FGP) may impart to pancreatic ductal adenocarcinoma (PDA) a deceptively benign appearance. Thus, its diagnosis on FNA is challenging. A case of PDA with FGP, that was suspected on Diff Quik smears, diagnosed on cell‐block preparation and confirmed by ancillary stains and molecular techniques, is here reported. The diagnostic interpretation of foamy atypical cells on direct smears may benefit from cell block preparation and from ancillary techniques. Diagn. Cytopathol. 2013. © 2012 Wiley Periodicals, Inc.     

Dissecting the presence of malignant squamous cells in pancreatic cytopathology: A case series

The presence of malignant squamous cells in pancreatic cytopathology is a rare phenomenon that results either from a primary or a metastatic process. Pancreatic adenosquamous carcinoma (PASC) represents the most common variant of pancreatic ductal adenocarcinoma and is associated with a dismal prognosis. Within the period of 2013‐2018, the archives of “Hygeia and Mitera Hospital” were searched for pancreatic cytopathology‐related diagnoses that included the interpretation of “malignant squamous cells present.” All fine needle aspirations (FNAs) of pancreatic lesions, including liver metastases in patients with known pancreatic primaries, were retrieved along with their relevant clinical information. Five pancreatic and two liver FNAs acquired from a total of six patients were reexamined. None of these patients had any documented history of primary squamous malignancy elsewhere. All pancreatic and one of the two liver FNAs showed malignant squamous cells, identified based on either morphology or immunochemistry. The other liver FNA represented a metastatic deposit which comprised of only a glandular component, whereas the associated pancreatic FNA exhibited both squamous and glandular counterparts. Most cases characteristically showed necrosis and keratinization. Of interest, two cases revealed the presence of tumor‐associated giant cells. In conclusion, the presence of malignant squamous cells in pancreatic FNAs could mean the presence of PASC, especially when there is no documented history of a primary malignancy and a complete clinical and imaging workup has been performed. Immunochemistry on cell block material could help to confirm squamous differentiation in the absence of overt keratinization.     

Guide to diagnosing primary pancreatic lymphoma, B-cell type: immunocytochemistry improves the diagnostic accuracy of endoscopic ultrasonography-guided fine needle aspiration cytology

Primary pancreatic lymphoma (PPL) is a rare disease with <1%of extranodal non-Hodgkin's lymphoma arising in the pancreas. This report provides immunocytochemical information on PPL that would be valuable for making differential diagnoses between PPL, pancreatic neuroendocine tumor, acinar cell carcinoma, and pancreatic ductal cancer. A 68-year-old woman had a chief complaint of abdominal pain. Fine needle aspiration cytology (FNAC)was performed. The FNAC smear showed moderate cellularity,with a small to moderate number of irregular cells and lymphocytes.No epithelial tumor clusters or abundant mucoid background were seen. The cells were scattered with pleomorphism and showed irregular nuclear shapes with finely granular chromatin,an increased nuclei–cytoplasm ratio, and prominent nucleoli.Cytologically, PPL was suspected with Papanicolaou staining but definite diagnosis was not made. Therefore, the specimen was destained, immunocytochemically examined for leukocyte common antigen (LCA), and PPL was suspected again. Numerous tumor cells were found in the surgical sample and tumor cells were positive for CD20 and negative for CD45RO. Based on these findings,the tumor was diagnosed as PPL, B-cell type. The preoperative FNAC smear that was examined for LCA was then reexamined for CD20, CEA, and Synaptophysin. As a result, the tumor cells were positive for LCA and CD20, whereas they were negative for CEA and Synaptophysin. Taking these findings together with the cytopathologic findings, this specimen was reconfirmed as PPL. Immunocytochemical examination for LCA and CD20 is useful in the identification of malignant pancreatic lymphoma, B-cell type.     

IgG4‐related disease of the paratestis with the scrotal fluid: A case report

IgG4‐related disease (IgG4‐RD) can affect various organs, and the pancreas and salivary gland are representative examples. We report a rare case of IgG4‐RD of the paratestis. A 74‐year‐old man presented with left scrotal swelling. Scrotopuncture drainage and cytology confirmed a clear, yellow retention liquid (130 mL) with many small, similar lymphocytes and a few plasmacytes. Many lymphoid cells were immunopositive for CD3 on a cell block section, indicating that a predominant type of lymphoid cells was T cell. There were also some CD20 immunopositive cells and a few IgG4 immunopositive cells. Two months later the left scrotal swelling had returned, and he underwent radical inguinal orchiectomy. Microscopically, there was considerable lymphoplasmacytic inflammatory infiltration, fibrosis and abundant IgG4 immunopositive cells in the paratesticular region. The histopathologic and immunohistochemistry findings were consistent with IgG4‐RD. However, the abundant T cells in the scrotal fluid complicated the cytological diagnosis in our case.     

A comparative needle study: EUS‐FNA procedures using the HD ProCore™ and EchoTip® 22‐gauge needle types

The specific needle sizes/types used in performing endoscopic ultrasound‐guided fine needle aspirations (EUS‐FNA) vary. The HD ProCore^? is a 22‐gauge beveled needle allowing for core biopsy along with aspiration material. In this study we compare this needle with a standard 22‐gauge needle. Between April 1, 2011 and November 15, 2011, 18 patients undergoing EUS‐FNA using the HD ProCore^? needle were compared to a control group of 18 cases using the standard 22‐gauge needle. Smears were assessed for: three‐dimensional clusters, thick obscuring clusters, monolayer sheets, cellularity, crowded obscuring single cells, blood, and nuclear staining. Cell blocks were assessed for cellularity and presence of diagnostic material. Records were reviewed for the overall adequacy, number of FNA passes, and patient follow‐up. Overall, the two needle groups demonstrated similar results for the cytology parameters, amount of diagnostic cell block material, adequacy, and accuracy. The mean number of passes to achieve adequacy varied between the groups [2.94 for the standard 22‐gauge needle group versus 2.11 for the beveled needle group (P=0.03)] with no meaningful difference in case duration between needle groups. No complications were reported. The beveled EUS needle affords similar cytologic interpretability, adequacy, diagnostic accuracy, and amount of cell block material as a standard needle. There was a statistically significant trend toward fewer passes to achieve adequacy with the beveled EUS‐FNA needle. Therefore, the EUS‐FNA needle with a lateral bevel is a diagnostically similar alternative to standard endoscopy needles, the possibility that this beveled needle may improve per pass adequacy requires further verification. Diagn. Cytopathol. 2013;41:1069–1074. © 2013 Wiley Periodicals, Inc.     

Immunocytochemical staining of smears and corresponding cell blocks from serous effusions: A follow-up and comparative investigation

Recently, we have recommended immunocytochemistry on serous effusions with the monoclonal antibodies Ber-EP4 and EMA to be used as a routine procedure. In this study, our earlier defined immunocytochemical profiles were tested in daily diagnostic work for a period and the profiles were applicated on the corresponding cell blocks from the effusions, too. It is concluded that routine use of the benign, malignant epithelial, and malignant mesothelial immunocytochemical profiles is valuable and superior to cytomorphology alone. Additionally, immunocytochemical staining of smears proved slightly more sensitive than immunohistochemistry performed on sections from the cell blocks. Diagn Cytopathol 1996;15:33–36. © 1996 Wiley-Liss, Inc.     

Cytologic features of pancreatic adenocarcinoma with “vacuolated cell pattern.” report of a case diagnosed by endoscopic ultrasound‐guided fine‐needle aspiration

The “vacuolated cell pattern” has only been recently described as a distinct morphologic variant of pancreatobiliary adenocarcinoma. Herein, we report the endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) cytologic features of a case of pancreatic adenocarcinoma with “vacuolated cell pattern” occurring in a 60‐year‐old man. The aspirate smears and cell block sections from the EUS‐FNA of a 23.5 mm hypoechoic pancreatic head mass were highly cellular, showing variably‐sized crowded three‐dimensional cell clusters, flat sheets, and numerous highly atypical single cells. The background was bloody and showed necrotic debris, but no discernible mucus. The most striking feature of the aspirate was the presence of numerous very large (20–50 µm) vacuoles, occupying the entire cytoplasm, pushing the nuclei to the side and indenting them, that imparted a cribriform appearance to the sheets of neoplastic cells. The non‐vacuolated neoplastic cells were large, had abundant dense (squamoid) cytoplasm, irregularly contoured hyperchromatic nuclei, and prominent macronucleoli. Histologic evaluation of the pancreatectomy specimen showed a “vacuolated cell pattern” adenocarcinoma composed of poorly formed glands, solid sheets, and infiltrating single cells with pleomorphic nuclei and large cytoplasmic vacuoles. To our knowledge, this is the first report describing the cytologic features of this rather uncommon morphologic variant of pancreatic adenocarcinoma. Recognition of this morphologic variant of pancreatic adenocarcinoma in ESU‐FNA samples allows its differentiation from primary and metastatic signet‐ring cell carcinomas. Diagn. Cytopathol. 2014;42:302–307. © 2014 Wiley Periodicals, Inc.     

Combination of MUC5ac and WT‐1 immunohistochemistry is useful in distinguishing pancreatic ductal carcinoma from ovarian serous carcinoma in effusion cytology

Malignant ascites may be the first presentation of an unsuspected cancer. Pancreas and ovary are among the organs that are usually evaluated as a source of primary. The purpose of this study is to investigate a panel of immunohistochemical stains to help differentiate pancreatic from ovarian carcinoma. We evaluated the immunohistochemical staining of eight commercially available antibodies MUC1, MUC2, MUC5ac, Wilm's tumor susceptibility gene 1 (WT1), cytokeratin 7 (CK7), CK20, CA125, and CA19.9 in 25 effusion specimens with evidence of metastatic carcinoma including 14 ovarian serous carcinomas, 9 pancreatic adenocarcinomas, and 2 unknown primaries. Primary ovarian serous carcinomas were positive for WT‐1 (100%), CK7 (93%), CK20 (43%), CA125 (100%), CA19.9 (50%), MUC1 (100%), MUC2 (0%), and MUC5ac (0%). Primary pancreatic carcinomas were positive for MUC5ac (100%), MUC1 (100%), CA19.9 (100%), CK7 (78%), CK20 (22%), CA125 (89%), WT‐1 (0%), and MUC 2 (0%). The combination of MUC5ac positivity/WT‐1 negativity was seen in 100% of pancreatic carcinoma, whereas MUC5ac negativity/WT‐1 positivity in 100% of ovarian serous carcinoma. It appears that the combination of MUC5ac and WT‐1 stains is useful in distinguishing pancreatic ductal from ovarian serous carcinoma in body fluid cytology. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

Ultrasound‐guided fine needle aspiration cytology in the diagnosis of hepatic and pancreatic perivascular epithelioid cell tumors: A case series

Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors that can affect any part of the body. They can be sporadic or arise in the setting of tuberous sclerosis (TSC). In this article, we report a series of three hepatic and two pancreatic PEComas diagnosed preoperatively with ultrasound‐guided fine needle aspiration (FNA). All patients were female (age range 28‐70), had no personal history of TSC and presented with a single, localized painless mass. Rapid on‐site evaluation (ROSE) of cytologic samples was performed for all cases to evaluate for cellular content and adequacy of specimens. Direct smears and cell block preparations revealed a proliferation of medium to large polygonal epithelioid cells, with abundant eosinophilic and vacuolated cytoplasm, arranged in sheets and nests. On immunohistochemistry (IHC), neoplastic cells showed co‐expression of melanocytic and smooth muscle markers and a diagnosis of PEComa was rendered. PEComas of the pancreas and liver are rare neoplasms, but should always be considered when examining “clear cell” neoplasms, especially in young female patients. If good quality cytologic samples are obtained by FNA, a correct diagnosis can be achieved with the help of IHC. This is of particular importance in order to plan adequate surgical strategy and to avoid overtreatment.     

Role of FNA cytology and immunochemistry in the diagnosis and management of medullary thyroid carcinoma: report of six cases and review of the literature

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine thyroid malignancy. This study retrospectively reviewed 10 fine-needle aspiration samples from six MTC patients. Aspirated specimens were from thyroid (3), cervical lymph nodes (5), left lung (1), and anterior chest wall (1). Cytomorphology consisted predominantly of plasmacytoid cells (3 cases), spindle cells (2 cases), and epithelioid cells (1 case). However, all specimens had a mixture of other cell types and "salt and pepper" chromatin. Only one specimen showed Congo-red-positive amyloid. Calcitonin was expressed in 7/7 specimens. Four patients underwent surgical excision and MTC was confirmed in all four. Follow-up studies included serum calcitonin (3/6 cases) and imaging (2/6 cases). One patient had MTC associated with multiple endocrine neoplasia IIA syndrome and one had familial MTC with a history of MTC in mother. In conclusion, the cytomorphology of MTC is typical and calcitonin immunostain is a reliable method for confirming primary or metastatic MTC. Early cytological diagnosis of MTC positively impacted patient management. Follow-up with serum calcitonin and imaging is helpful in the early detection of recurrences.     

Granulocyte colony‐stimulating factor‐producing pancreatic anaplastic carcinoma in ascitic fluid at initial diagnosis: A case report

Granulocyte colony‐stimulating factor (G‐CSF)‐producing pancreatic tumors are extremely rare. These tumors have an aggressive clinical course and no established treatment. Here, we report an autopsy case of G‐CSF‐production in pancreatic anaplastic carcinoma (PAC). A 72‐year‐old woman presented with a large pancreatic head mass and multiple liver metastases. Laboratory data showed leukocytosis (leukocyte count 113.3 × 10³/µL) and high serum G‐CSF levels (441 pg/mL; normal range: <39.0 pg/mL). The ascitic fluid was submitted to our pathology laboratory at initial diagnosis. Cytopathology showed that smears from the ascitic fluid were highly cellular and contained numerous malignant cells, mainly in loose groupings. Occasional pseudoglandular formations and giant cells were also present. The malignant cells were round, and no spindle‐shaped cells were visible. The nuclei were round to ovoid with coarsely granular chromatin and large prominent nucleoli. Upon immunocytochemistry, tumor cells were positive for G‐CSF and vimentin; there was no E‐cadherin expression. Histopathological examination of the tumor showed a mixed composition of adenocarcinomatous and sarcomatous regions. Upon immunohistochemistry, both components were positive for G‐CSF. Few CD34‐positive myeloblasts were observed in the bone marrow. Thus, we diagnosed this as a case of G‐CSF production in PAC with leukocytosis. To the best of our knowledge, this is the first report on G‐CSF expression immunocytochemically confirmed in PAC. Diagn. Cytopathol. 2017;45:463–467. © 2017 Wiley Periodicals, Inc.     

Large platelet aggregates in endoscopic ultrasound‐guided fine‐needle aspiration of the pancreas and peripancreatic region: A clue for the diagnosis of intrapancreatic or accessory spleen

Intrapancreatic and intraabdominal accessory spleens (IPIASs) are rarely encountered in endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) biopsies. However, as incidentally discovered IPIAS can mimic a benign or malignant pancreatic neoplasm on imaging studies, a definitive diagnosis made by EUS‐FNA can avert an unnecessary surgical intervention or additional radiologic follow‐up. We report five cases of intrapancreatic splenules and one case of accessory spleen (AS) in which a definitive diagnosis was made on EUS‐FNA. Previously recognized FNA cytomorphologic features of splenic tissue, including ASs and splenosis, are endothelial cells and polymorphous lymphocytes admixed with neutrophils, eosinophils, plasma cells, histiocytes, and lymphoglandular bodies. We describe the additional finding of abundant large platelet aggregates as another distinguishing feature of splenic tissue on FNA. In all six cases, large platelet aggregates were identified along with polymorphous lymphoid cells, lymphoglandular bodies, loose aggregates of endothelial cells and scattered or aggregated bland spindle cells. A review of 10 consecutive cases of EUS‐FNA‐sampled benign intraabdominal lymph nodes showed that the presence of large platelet aggregates, three‐dimensional aggregates of lymphoid cells and of bland slender spindle cells and the absence of follicular germinal cell components (tingible body macrophages and lymphohistiocytic aggregates) are useful in differentiating IPIASs from reactive lymph nodes. Immunoperoxidase stains were useful to confirm a suspected IPIASs by showing CD31‐positive acellular flocculent material, consistent with large platelet aggregates and a rich CD8‐positive endothelial cell network between CD45‐positive lymphoid cells and CD68‐positive histiocytes in all six cases. Diagn. Cytopathol. 2013;41:661–672. © 2013 Wiley Periodicals, Inc.     

Fine-needle aspiration cytology of pancreatic somatostatinoma: the importance of immunohistochemistry for the cytologic diagnosis of pancreatic endocrine neoplasms

Pancreatic somatostatinoma is a rare pancreatic endocrine neoplasm representing as little as 1% of pancreatic endocrine neoplasms (PENs). The histologic features of this tumor are like those of other PENs, except that it commonly forms acinar structures and often has cells with abundant, granular cytoplasm. We have recently encountered two of these neoplasms sampled by endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA). We discuss the cytologic and immunohistochemical findings of these two cases and the cytologic similarities these neoplasms share with pancreatic acinar-cell carcinoma (PACC). We review the cytologic features of PEN and PACC and discuss the importance of cell block immunohistochemistry in the diagnosis of pancreatic neoplasia sampled by EUS-guided FNA.     

Significance of the diagnostic categories “atypical” and “suspicious for malignancy” in the cytologic diagnosis of solid pancreatic masses

Endoscopic ultrasound guided (EUS) fine‐needle aspiration (FNA) investigation of solid pancreatic lesions has been shown to have good sensitivity and specificity. Many lesions can be definitely classified as benign or malignant but some can only be cytologically classified as “atypical” or “suspicious for malignancy”. Risk for malignancy in these indeterminate categories has not been well categorized. The cytology records of four University Medical centers were searched for all EUS guided FNAs of solid pancreatic lesions. All cases with a diagnosis of “atypical”, or “suspicious for malignancy” were selected for analysis when histologic biopsy or over 18 months clinical follow‐up was available. Two hundred and ninety‐two cases with a diagnosis of “atypical” or “suspicious for malignancy” and adequate follow‐up were obtained from the combined data of the four institutions. The percentage malignant for the categories “atypical” and “suspicious for malignancy” were 79.2 and 96.3%, respectively. If the category “atypical” was classified as benign and “suspicious for malignancy” was classified as malignant, the resulting positive predictive value was 96.3 (95% CI: 92.6–98.5) and the negative predictive value 20.8 (95% CI: 13.4–30.0). The categories of “atypical” and “suspicious for malignancy” stratify risk for malignancy in a fashion, which may aid in patient counseling and selection of follow‐up protocols. Classification of “suspicious for malignancy” as malignant optimizes diagnostic sensitivity and specificity. Diagn. Cytopathol. 2014;42:292–296. © 2014 Wiley Periodicals, Inc.     

An immunohistochemical examination of the expression of E-cadherin, α- and β/γ-catenins,and α2- and β1-integrins in invasive breast cancer

This study examines the expression of the cell–cell adhesion molecules E-cadherin and its associated proteins, the catenins and the matrix–cell adhesion molecules β1- and α2-integrins, in primary invasive breast carcinoma. Expression was assessed immunohistochemically on frozen sections by semi-quantitative scoring of the intensity and proportion of immunoreactivity in 55 cases. Associations with each other and with other histological and prognostic features and survival were sought. There was a significant association between loss of E-cadherin expression and loss of α- and β/γ-catenin immunostaining. In 20 per cent of cases, membranous immunoreactivity with E-cadherin antibody was absent. Absent cytoplasmic expression of α- and β/γ-catenins was seen in 24 and 22 per cent of breast cancers, respectively. The intensity of reactivity with E-cadherin showed a significant association with histological grade (p = 0·002) and tumour type (p < 0·001). Lobular carcinomas frequently showed loss of expression of E-cadherin, as reported elsewhere; loss of catenin expression was also found in these tumours. α-Catenin intensity also showed a relationship with grade (p = 0·008) and with oestrogen receptor (ER) status (p = 0·006). β/γ-Catenin expression was not associated with other known prognostic factors. Forty-nine per cent and 42 per cent of cases showed no membrane immunostaining with β1- and α2-integrin, respectively, and co-ordinated loss of β1- and α2-integrin expression was found. Both β1- and α2-integrin expression were associated with histological grade (p = 0·003 and p = 0·031, respectively) and β1 immunoreactivity with tumour type (p = 0·010). None of the variables examined showed a statistically significant association with tumour size or lymph node stage, or with overall survival, although a trend was seen (p = 0·087) towards poorer survival of patients with tumours with absent or weak expression of β1-integrin. The expression of these markers is of biological interest, but appears to be of little additional use in predicting clinical behaviour. Copyright © 1999 John Wiley & Sons, Ltd.     

Secondary tumors of the pancreas diagnosed by endoscopic ultrasound‐guided fine‐needle aspiration: A 10‐year experience

Determining whether a pancreatic mass is a primary or secondary neoplasm is necessary for appropriate treatment. We reviewed our experience using endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) for diagnosis of pancreatic tumors to identify clinical and cytopathologic characteristics of metastatic disease. We reviewed all cases of tumors metastatic to the pancreas evaluated at The University of Texas MD Anderson Cancer Center and The Methodist Hospital in Houston, Texas during the period from 2002 to 2012. The review included cytologic specimens, clinical history, radiologic findings, primary tumor type, and clinical follow‐up. We identified 66 patients with disease metastatic to the pancreas for which cytologic material was available: 38 (58%) men and 28 (42%) women, with an average age of 63 years (range, 40–89 years). Most metastases (98%) were single lesions, and nearly half were located in the head of the pancreas (30/66). The most common site of origin for these metastases was kidney (27 [41%] cases). Follow‐up information was available for 65 (98%) patients, and duration of follow‐up ranged from <1 to 10 years (mean, 2.3 years). Thirty‐three patients (50%) were alive at the time of the most recent follow‐up contact. Of the 25 patients with metastatic renal cell carcinoma, clear cell type, 19 (76%) were alive at the time of the most recent follow‐up. It was concluded that metastases may mimic primary pancreatic carcinomas both clinically and cytologically. Ancillary studies in conjunction with clinical history are necessary for the accurate diagnosis of FNAs of secondary pancreatic tumors. Diagn. Cytopathol. 2014;42:738–743. © 2014 Wiley Periodicals, Inc.