Mucin-producing Adenocarcinomas Research Articles

Colloid Pattern of Salivary Mucinous Adenocarcinomas With Recurrent BRAF V600E Mutations.

The relationship between various patterns of mucin-producing salivary adenocarcinomas, including invasive salivary adenocarcinomas with mucinous differentiation, such as colloid and papillary carcinomas, remains unclear. Herein, we aimed to describe the clinicopathologic characteristics, immunophenotypes, molecular underpinnings, and clinical behavior of salivary mucinous adenocarcinomas (MA) to clarify their classification. We described a broad series of colloid and papillary patterns of MAs, indicating that papillary pattern presented papillary cystic proliferation of mucinous columnar cells as salivary intraductal papillary mucinous neoplasms with recurrent AKT1 E17K mutations, whereas colloid adenocarcinomas containing large mucinous pools or lakes around the malignant epithelial nests or islands harbored BRAF V600E mutations with worse prognosis. Typical morphologic structures, CK7(+), CK20(-), CDX2(-), p63(-), p40(-), MAML2 fluorescence in situ hybridization (-), AR(-), TTF-1(-), S100(-), mammaglobin(-), or S100/mammaglobin(+) with ETV6 fluorescence in situ hybridization (-) immunophenotype, and recurrent AKT1 E17K or BRAF V600E mutations may be defined. To our knowledge, this small series represents the first genetic study on a typical colloid pattern of MA, and our study with the spectrum documentation for MA in clinicopathologic characteristics, histologic and immunophenotypes, molecular features, and clinical behavior will allow for a better understanding of these rare but distinctive tumors.

Abstract 6035: Genetically-engineered mouse model for colonic neoplasia presenting mucinous and microsatellite unstable phenotype

Abstract Background and Aim: Mucinous colorectal adenocarcinoma (CRC) is characterized by abundant extracellular mucin which occupies more than 50% of the tumor volume. Mucinous CRCs account for 10% of all CRCs and are likely to be microsatellite unstable including Lynch syndrome. Mucinous CRCs metastasize less frequently. However, once they metastasize, they exhibit resistance to cytotoxic chemotherapeutics, and are associated with poorer prognosis. Although there are some issues to be addressed in mucinous CRCs, mouse models are lacking for mucinous CRCs. Here, we report genetically-engineered mouse models (GEMMs) for mucin-producing colonic tumors with microsatellite instability (MSI), resembling human mucinous CRCs. Method: To induce genetic alterations specifically in colonic epithelial cells, we used CDX2P-G19Cre transgenic mice. In this mouse model, a 9.5-kb fragment in the CDX2 promoter lesion (CDX2P9.5) regulates Cre expression specifically in colonic epithelium (Hinoi et al. Cancer Research 2007). In addition, 19 guanine nucleotides are inserted just after the first ATG, and Cre only expresses in the epithelial cells in which the number of the guanine tract stochastically turns a multiple of three. This mechanism helps our GEMMs to avoid embryonic death due to the genetic events we introduce. We have also reported that tumors in CDX2P9.5-G19Cre;Apcflox/flox mice have an abnormality in two of four MSI markers, suggesting that the tumors are driven by MSI (Sasada et al. PLoS One 2015). TGFBR2 mutation is frequently seen in human MSI CRCs, and inactivation of both Tgfrbr2 and Apc by Villin-Cre results in small intestinal neoplasm producing mucin. Therefore, to test if Tgfbr2 conditional knockout affects the mucin-producing phenotype in the context of MSI-high in this mouse model, we generated CDX2P-G19Cre;Apcflox/+;Tgfbr2flox/flox. Results: In CDX2P-G19Cre; Apcflox/+; Tgfbr2 flox/flox mice, colonic neoplasia developed in 27 out of 40 mice. Approximately 60% of the tumors are well-differentiated adenocarcinoma producing mucin, while the remaining 40% are regular colonic adenomas. In these mucinous adenocarcinomas, tumor cells invade into the muscular layer. We also confirmed the immunoreactivity of β-catenin in cytoplasm and nuclei at the invasive front of the tumors in IHC analysis, indicating that these tumors are driven by abnormal Wnt activity. Nearby to the invasive front, there were mucin that were positive for a PAS reaction. Conclusion: Mucin-producing adenocarcinomas develop in CDX2P9.5-G19Cre;Apcflox/+; Tgfbr2flox/flox mice. This GEMM is a potential mouse model recapitulating human mucinous and microsatellite unstable colorectal adenocarcinoma. The precise mechanism in which mucinous adenocarcinoma develops needs to be elucidated by genomic and transcriptomic analyses. Citation Format: Haruki Sada, Takao Hinoi, Hiroaki Niitsu, Masashi Miguchi, Naoya Sakamoto, Naohide Oue, Hirotaka Tashiro, Hideki Ohdan. Genetically-engineered mouse model for colonic neoplasia presenting mucinous and microsatellite unstable phenotype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6035.

Pathological, molecular, and clinical characteristics of cholangiocarcinoma: A comprehensive review.

Cholangiocarcinomas are a heterogeneous group of highly aggressive cancers that may arise anywhere within the biliary tree. There is a wide geographical variation with regards to its incidence, and risk-factor associations which may include liver fluke infection, primary sclerosing cholangitis, and hepatolithiasis amongst others. These tumours are classified into intrahepatic, perihilar and distal based on their anatomical location. Morphologically, intrahepatic cholangiocarcinomas are further sub-classified into small and large duct variants. Perihilar and distal cholangiocarcinomas are usually mucin-producing tubular adenocarcinomas. Cholangiocarcinomas develop through a multistep carcinogenesis and are preceded by dysplastic and in situ lesions. While clinical characteristics and management of these tumours have been extensively elucidated in literature, their ultra-structure and tumour biology remain relatively unknown. This review focuses on the current knowledge of pathological characteristics, molecular alterations of cholangiocarcinoma, and its precursor lesions (including biliary intraepithelial neoplasia, intraductal papillary neoplasms of the bile duct, intraductal tubulopapillary neoplasms and mucinous cystic neoplasm).

Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Salivary Glands.

The salivary gland section in the 5th edition of the World Health Organization Classification of Head and Neck Tumours features a description and inclusion of several new entities, including sclerosing polycystic adenoma, keratocystoma, intercalated duct adenoma, and striated duct adenoma among the benign neoplasms; and microsecretory adenocarcinoma and sclerosing microcystic adenocarcinoma as the new malignant entities. The new entry also includes mucinous adenocarcinoma subdivided into papillary, colloid, signet ring, and mixed subtypes with recurrent AKT1 E17K mutations across patterns suggesting that mucin-producing salivary adenocarcinomas represent a histologically diverse single entity that may be related to salivary intraductal papillary mucinous neoplasm (IPMN). Importantly, the number of entities in the salivary chapter has been reduced by omitting tumors or lesions if they do not occur exclusively or predominantly in salivary glands, including hemangioma, lipoma, nodular fasciitis and hematolymphoid tumors. They are now discussed in detail elsewhere in the book. Cribriform adenocarcinoma of salivary gland origin (CASG) now represents a distinctive subtype of polymorphous adenocarcinoma (PAC). PAC is defined as a clinically, histologically and molecularly heterogeneous disease group. Whether CASG is a different diagnostic category or a variant of PAC is still controversial. Poorly differentiated carcinomas and oncocytic carcinomas are discussed in the category "Salivary carcinoma not otherwise specified (NOS) and emerging entities". New defining genomic alterations have been characterized in many salivary gland tumors. In particular, they include gene fusions, which have shown to be tightly tumor-type specific, and thus valuable for use in diagnostically challenging cases. The recurrent molecular alterations were included in the definition of mucoepidermoid carcinoma, adenoid cystic carcinoma, secretory carcinoma, polymorphous adenocarcinoma, hyalinizing clear cell carcinoma, mucinous adenocarcinoma, and microsecretory adenocarcinoma.

Salivary Mucinous Adenocarcinoma Is a Histologically Diverse Single Entity With Recurrent AKT1 E17K Mutations: Clinicopathologic and Molecular Characterization With Proposal for a Unified Classification.

Mucin-producing salivary adenocarcinomas were historically divided into separate colloid carcinoma, papillary cystadenocarcinoma, and signet ring cell carcinoma diagnoses based on histologic pattern, but have recently been grouped together in the adenocarcinoma not otherwise specified category. It is currently unclear if these tumors represent 1 or more distinct entities and how they are related to well-circumscribed papillary mucinous lesions with recurrent AKT1 E17K mutations that were recently described as salivary intraductal papillary mucinous neoplasm. Here, we sought to evaluate the clinicopathologic and molecular features of salivary mucinous adenocarcinomas to clarify their classification. We identified 17 invasive mucin-producing salivary adenocarcinomas, 10 with a single histologic pattern, and 7 with mixed patterns. While most tumors demonstrated papillary growth (n=15), it was frequently intermixed with colloid (n=6) and signet ring (n=3) architecture with obvious transitions between patterns. All were cytokeratin 7 positive (100%) and cytokeratin 20 negative (0%). Next-generation sequencing performed on a subset demonstrated recurrent AKT1 E17K mutations in 8 cases (100%) and TP53 alterations in 7 cases (88%). Of 12 cases with clinical follow-up (median: 17 mo), 4 developed cervical lymph node metastases, all of which had colloid or signet ring components. Overall, overlapping histologic and immunohistochemical features coupled with recurrent AKT1 E17K mutations across patterns suggests that mucin-producing salivary adenocarcinomas represent a histologically diverse single entity that is closely related to tumors described as salivary intraductal papillary mucinous neoplasm. We propose a unified mucinous adenocarcinoma category subdivided into papillary, colloid, signet ring, and mixed subtypes to facilitate better recognition and classification of these tumors.

Anatomical, histomorphological and molecular classification of cholangiocarcinoma.

Cholangiocarcinoma constitutes a heterogeneous group of malignancies that can emerge at any point of the biliary tree. Cholangiocarcinoma is classified into intrahepatic, perihilar and distal based on its anatomical location. Histologically, conventional perihilar/distal cholangiocarcinomas are mucin-producing adenocarcinomas or papillary tumours; intrahepatic cholangiocarcinomas are more heterogeneous and can be sub-classified according to the level or size of the displayed bile duct. Cholangiocarcinoma develops through multistep carcinogenesis and is preceded by dysplastic and in situ lesions. Definition and clinical significance of precursor lesions, including biliary intraepithelial neoplasia, intraductal papillary neoplasms of the bile duct, intraductal tubulopapillary neoplasms and mucinous cystic neoplasm, are discussed in this review. A main challenge in diagnosing cholangiocarcinoma is the fact that tumour tissue for histological examination is difficult to obtain. Thus, a major clinical obstacle is the establishment of the correct diagnosis at a tumour stage that is amenable to surgery which still represents the only curable therapeutic option. Current standards, methodology and criteria for diagnosis are discussed. Cholangiocarcinoma represents a heterogeneous tumour with regard to molecular alterations. In intrahepatic subtype, mainly two distinctive morpho-molecular groups can currently be discriminated. Large-duct type intrahepatic cholangiocarcinoma shows a high mutation frequency of oncogenes and tumour suppressor genes, such as KRAS and TP53 while Isocitrate Dehydrogenase 1/2 mutations and Fibroblast Growth Factor Receptor 2-fusions are typically seen in small-duct type tumours. It is most important to ensure the separation of the given anatomical subtypes and to search for distinct subgroups within the subtypes on a molecular and morphological basis.

Extracellular fluid viscosity enhances liver cancer cell mechanosensing and migration

The extracellular fluid (ECF) is a crowded environment containing macromolecules that determine its characteristic density, osmotic pressure, and viscosity, which greatly differ between tissues. Precursors and products of degradation of biomaterials enhance ECF crowding and often increase its viscosity. Also, increases in ECF viscosity are related to mucin-producing adenocarcinomas. However, the effect of ECF viscosity on cells remains largely unexplored. Here we show that viscosity-enhancing polymer solutions promote mesenchymal-like cell migration in liver cancer cell lines. Also, we demonstrate that viscosity enhances integrin-dependent cell spreading rate and causes actin cytoskeleton re-arrangements leading to larger cell area, nuclear flattening, and nuclear translocation of YAP and β-catenin, proteins involved in mechanotransduction. Finally, we describe a relationship between ECF viscosity and substrate stiffness in determining cell area, traction force generation and mechanotransduction, effects that are actin-dependent only on ≤ 40 kPa substrates. These findings reveal that enhancing ECF viscosity can induce major biological responses including cell migration and substrate mechanosensing.

CEACAM6 as detected by the AP11 antibody is a marker notable for mucin-producing adenocarcinomas

A new monoclonal antibody recognizing CEACAM6, which we named AP11, was generated by immunizing BALB/c mice with phytohemagglutinin-activated human peripheral blood mononuclear cells. This study aims to evaluate whether CEACAM6 can serve as a tumor marker using AP11. We examined the expression of CEACAM6 with AP11 in 11 human carcinoma cell lines by flow cytometry and 439 human tissues including 282 tumor tissues and 157 normal tissues by immunohistochemistry. CEACAM6 epitope recognized by AP11 was well preserved in formalin-fixed and paraffin-embedded tissues. Adenocarcinomas of the stomach (86 %), colorectum (95 %), pancreas (100 %), and lung (83 %), urinary bladder (100 %), and mucinous ovarian tumors (88 %) had a high rate of CEACAM6 immunoreactivity. We observed a variable expression of CEACAM6 in hepatocellular carcinomas (35 %), squamous cell carcinomas of the lung (60 %), renal cell carcinomas (14 %), urothelial carcinomas (13 %), serous carcinomas of the ovary (17 %), and breast carcinomas (11 %). Small-cell carcinomas of the lung, prostatic adenocarcinomas, papillary thyroid carcinomas, malignant melanomas, giant cell tumors, and osteosarcomas were negative for CEACAM6. All normal tissues of various organs were negative for CEACAM6. In conclusion, CEACAM6 as detected by AP11, may serve as a marker for mucin-producing adenocarcinomas of the gastrointestinal tract and ovary as well as non-small cell lung cancer. Thus, AP11 represents a valuable diagnostic tool for detecting CEACMA6-positive cancers.

Napsin-A, TTF-1, EGFR, and ALK Status Determination in Lung Primary and Metastatic Mucin-Producing Adenocarcinomas

Pulmonary mucin-producing adenocarcinomas may be indistinguishable on conventional histology from a metastasis, as thyroid transcription factor-1 (TTF-1) expression often is lacking and KRAS mutations are widely present even in extrapulmonary sites. Few data have been reported on the diagnostic role of napsin-A and epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) gene alterations in this challenging differential diagnosis. Seventy-seven surgically resected cases, including 53 primary and 24 metastatic tumors from different sites, were evaluated for napsin-A, TTF-1, and ALK by immunohistochemistry and for EGFR mutations by direct sequencing. Overall, napsin-A expression in primary lung mucin-producing adenocarcinomas was 36% (8% mucinous, 17% colloid, 87.5% solid, and 100% signet ring cell) and TTF-1 expression reached an overall figure of 42% (12.5% mucinous, 33% colloid, 87.5% solid, and 100% signet ring cell). Metastatic mucinous adenocarcinomas did not react with napsin-A or with TTF-1. All primary and metastatic tumors lacked EGFR mutations, while a single case of signet ring cell lung adenocarcinoma showed ALK expression and rearrangement at fluorescent in situ hybridization analysis. Napsin-A has a lower sensitivity compared with TTF-1 in primary mucin-producing adenocarcinomas of the lung. However, both antibodies have an absolute specificity, being always negative in metastatic mucinous adenocarcinomas. EGFR mutations and ALK translocation or expression are exceedingly rare in mucin-producing adenocarcinomas of the lung, resulting unnecessary as diagnostic tool in this setting.

Pancreatic Cyst Prevalence and the Risk of Mucin-Producing Adenocarcinoma in US Adults

The presence of a pancreatic cyst often prompts concern, although the rate of malignant transformation to mucin-producing adenocarcinoma is not known. We aimed to determine the prevalence rate of mucin-producing adenocarcinoma in US adults with pancreatic cysts. This retrospective, population-based cross-sectional study calculated the annual number of mucin-producing adenocarcinomas using the Surveillance Epidemiology and End Results (SEER 18) database and the 2010 US census. The overall prevalence rate of cysts in the population was found using data from large cross-sectional imaging studies of incidental cyst prevalence. Prevalence rates were then calculated by dividing the annual number of mucin-producing adenocarcinomas by the cyst prevalence rate. Between 2005 and 2009, 1,137 mucin-producing adenocarcinomas were estimated to be found annually in a US adult population of 137,154,960. The total number of pancreas cysts, given a cyst prevalence rate of 2.5%, was 3,428,874. Therefore, the prevalence rate of mucin-producing adenocarcinoma arising in patients with pancreatic cysts was 33.2 per 100,000 (95% confidence interval (CI): 21.9-44.5). The prevalence rate was 32.8 per 100,000 (95% CI: 21.6-44.0) in women and 33.5 per 100,000 (95% CI: 22.2-44.8) in men. As expected, the rate of malignant transformation increased linearly with advancing age (highest 38.6 per 100,000 in 80- to 84-year-old men). Malignant transformation of pancreatic cysts into mucin-producing adenocarcinoma in US adults is a very rare event. Current clinical guidelines and resource allocation for pancreatic cyst disease should be reconsidered given these findings.

Primary urachal malignancy: case report and literature review

Dear Editor, We present the case of a 38-year-old nulliparous woman who presented with a 3 months history of lower abdominal pain, dysuria and frequency. She denied weight loss, altered bowel habit or PR bleeding. Examination revealed a pelvic mass palpable to the level of the umbilicus. It was firm, non-tender and immobile. Hb was 9.6 g/dl and CA 125 was 18 U/ml. Her liver function tests, urea and electrolytes were within normal limits. Past history included emergency surgery at 3 days of life for Meckels diverticulum, atrial septal defect repair at 7 years of age and an appendectomy at 8 years of age. She had no previous gynae history or family history of breast, ovarian or bowel carcinoma. An abdominal and pelvic CT scan revealed a 9.5 9 7.7 cm midline abdominal mass suspicious for ovarian malignancy (Figs. 1, 2). The mass appeared adherent to the anterior abdominal wall had irregular margins and fat stranding. It indented small bowel loops and possible invasion of the small bowel was suggested. A further multi-cystic lesion was seen in the left adnexa. No pleural effusion or ascites were present. Multiple mesenteric nodes of 1 cm in diameter were present. She was referred to a tertiary gynaecology oncology centre where a laparotomy was performed with a colorectal surgeon present. She was found to have situs inversus of the abdominal organs, an absent right ovary and fallopian tube and normal left ovary and fallopian tube. The tumour was adherent to the anterior abdominal wall and to the bladder posteriorly. A frozen section confirmed metastatic mucinous adenocarcinoma consistent with an ovarian primary. Also present was a healthy appendix although situated in the left iliac fossa. The mass was resected en bloc (Fig. 3) including much of the rectus muscle, the dome of the bladder, two loops of small bowel and a right hemicolectomy was performed. A simple cystic left paraovarian mass was also removed. Histology showed a signet-ring mucinous adenocarcinoma of the urachus (10 cm) extending from the dome of the bladder with full thickness invasion of the small bowel and inflammatory adhesions to large bowel. All bowel, bladder and soft tissue margins were free of tumour. A normal appendix was noted. 31 lymph nodes isolated were free of tumour. The para-ovarian mass showed signet-ring mucinous adenocarcinoma also consistent with metastasis from urachal malignancy. Peritoneal washings were negative. She recovered well postoperatively and was referred to urology for discussion re-adjuvant chemotherapy. The urachus is a midline vestigial remnant located between the dome of the bladder and the umbilicus (Fig. 4). In the foetus the urachus connects the bladder to the allantois. In normal development the allantois is gradually reduced and obliterated with the urachus becoming a fibrous band extending from the anterior bladder dome to the umbilicus. Primary adenocarcinoma of the bladder accounts for less than 1 % of all bladder malignancies, of these 20–39 % are urachal in origin. Urachal adenocarcinoma is more common in men and tends to present in the fifth and sixth decade of life. The common presenting symptoms are haematuria, pain, irritative voiding symptoms and mucosuria. Most urachal malignancies (70 %) are mucin-producing adenocarcinomas, more rarely it is a non-mucin producing adenocarcinoma (15 %). Consistent with other enteric type adenocarcinomas, urachal cancers may express detectable D. Hayes Ryan (&) P. Paramanathan N. Russell J. Coulter South Infirmary Victoria University Hospital, Cork, Ireland e-mail: dee_hayes_ryan@hotmail.com

Napsin A Expression in Primary Mucin-Producing Adenocarcinomas of the Lung

Immunohistochemical expression of napsin A in primary pulmonary mucinous tumors is not well established. Napsin A immunoreactivity was evaluated in 43 mucin-producing adenocarcinomas of the lung consisting of 18 tumors formerly classified as mucinous bronchioloalveolar carcinoma, 15 colloid adenocarcinomas, 5 solid predominant adenocarcinomas with mucin production, and 5 adenocarcinomas with signet ring cell features, as well as in 25 extrapulmonary mucinous adenocarcinomas of different anatomic sites. Immunohistochemical expression of thyroid transcription factor 1 (TTF-1) was also compared. Thirty-three percent of mucinous lung tumors exhibited positive immunoreactivity for napsin A, whereas 42% expressed TTF-1. All 25 extrapulmonary mucinous adenocarcinomas lacked expression of napsin A and TTF-1. Mucin-producing neoplasms of the lung infrequently express napsin A, suggesting that immunohistochemical assessment of napsin A may have limited diagnostic usefulness for distinguishing primary and metastatic mucinous adenocarcinomas involving the lung.

Clinicopathological characterization of mammary analogue secretory carcinoma of salivary glands

Mammary analogue secretory carcinoma (MASC) is a recently described tumour with ETV6 translocation. We aimed to characterize the clinical significance of recognizing MASC. Thirty-six patients with MASC (27 identified retrospectively and nine prospectively) are presented. Historically, MASC mimicked other salivary tumours, as follows: 14 of 37 (37.8%) adenocarcinoma, not otherwise specified, 11 of 89 (12.4%) acinic cell carcinomas (AciCC), one of five (20%) mucin-producing signet ring adenocarcinomas, and one of 165 (0.6%) mucoepidermoid carcinomas. Demographically, MASC affected males more commonly (1.4:1). The average age at diagnosis was 45.7 years. Parotid gland was the most common site of involvement (26 of 36, 72.2%), although other head and neck sites, including the base of tongue, were affected. Of 18 patients with neck dissection, lymph node involvement was identified in four patients (four of 18, 22.2%). Survival analysis of MASC cases presented here, combined with those reported previously, revealed a mean disease-free survival for patients with MASC of 92 months [n = 29; 95% confidence interval (CI) 71-115 months], compared with a mean DFS of 121 months for patients with AciCC (n = 38; 95% CI 92-149, P = 0.43). Although perhaps slightly more aggressive, MASC clinical outcome mimics that of AciCC.

Signet ring cell adenocarcinoma of the oropharynx: Presentation of a rare case and review of the literature

Intracellular mucin-producing adenocarcinomas, so called signet ring cell adenocarcinomas (SRCAs), are most commonly found in the stomach or lower GI-tract. They occur far less frequently at other locations such as prostate, pancreas, mammarian gland or within the oropharyngeal cavity. We present the case of a patient who suffered from indolent cervical nodular tumour. Biopsy and histopathological workup showed parts of a poorly differentiated SRCA with p53 overexpression and mutations. Immunostaining gave no further hints for the origin of the malignancy. Thorough staging revealed an extended tumour of the oropharynx as primary origin. The definitive surgical therapy consisted of a transoral tumour resection with CO 2-laser and bilateral neck dissection. Final classification was pN2c cM0 G3 R0 L1 V0. Adjuvant fractioned radiotherapy with 66 Gy was applied because of bilateral lymph node metastases and extracapsular spread. So far only few cases of oropharyngeal SRCAs have been published. These tumours turned out to be either metastases from gastric or lower gastrointestinal primaries, or had the small salivary glands as origin. In all published cases, as well as in our case, radical surgical resection was the first step of a curative therapy trial. Adjuvant targeted therapy with drugs like, e.g. herceptin or imatinib was not possible because of genetic and immunhistochemical findings. Because of the small numbers of published cases, an evaluation long-term outcomes and significance of different adjuvant therapy regimes is barely possible at this time.

Cytological features of signet‐ring cell carcinoma of the lung: Comparison with the goblet‐cell‐type adenocarcinoma of the lung

Signet-ring cell carcinoma (SRCC) and goblet-cell-type adenocarcinoma (GCA) are mucin-producing lung adenocarcinomas. Primary SRCC shows an aggressive clinical course, whereas GCA shows infrequent distant metastasis, but more frequent intrapulmonary metastases resembling lobar pneumonia. To distinguish SRCC from GCA, this study investigated the respective cytological features of these lesions. We selected 10 cases each of SRCC and GCA from the archival imprint smears. We assessed them for the following 10 cytological features. Necrosis/debris was observed in 60% of the SRCC and 90% of the GCA. A mucinous background was observed in 10% of the SRCC and 90% of the GCA. Significant inflammation was observed in none of the SRCC and 80% of the GCA. Stromal cluster was observed in 30% of the SRCC and 70% of the GCA. Nuclear overlapping was observed in 50% of the SRCC and in all of the GCA. Single tumor cells were observed in 80% of the SRCC and 10% of the GCA. Honeycomb-like cluster was observed in none of the SRCC and 80% of the GCA. Prominent nucleolus was observed in 50% of the SRCC and 40% of the GCA. Nuclear membrane irregularity was observed in 70% of SRCC and 60% of the GCA. Nuclear pleomorphism was observed in all of the SRCC and none of the GCA. The cytological features of SRCC were the presence of single tumor cells and nuclear pleomorphism, whereas that of GCA were the presence of abundant mucin and significant inflammation in the background, and a honeycomb-like cluster.

Osseous Metaplasia of the Colon in a Diversion Proctocolitis

Osseous metaplasia within the gastrointestinal tract is a rare phenomenon, seen most frequently in mucinproducing left-sided colonic adenocarcinomas. It has also been documented in a variety of benign conditions, occurring in polyps and lesions associated with inflammation and ulceration. This is the first case report, to the authors' knowledge, of osseous metaplasia associated with a diversion proctocolitis. The diversion was performed following stricture formation, secondary to complicated diverticular disease with diverticular phlegmon formation. In common with other cases, in which osseous metaplasia arises within a background of inflammation, the present case demonstrated stromal fibroblastic proliferation. The underlying pathogenesis of osseous metaplasia has not yet been elucidated, but secretion of various bone morphogenic proteins (belonging to the transforming growth factor-beta superfamily) and increased alkaline phosphatase activity by both epithelial and stromal cells have been documented.

2148: Prognostic Factors and Impact of Adjuvant Radiotherapy and Chemotherapy on Resected Mucinous Adenocarcinomas of the Pancreas

2148: Prognostic Factors and Impact of Adjuvant Radiotherapy and Chemotherapy on Resected Mucinous Adenocarcinomas of the Pancreas

De novo calcification of liver and nodal metastases in prostate carcinoma

Prostate cancer has a distinctly recognized pattern of metastases: multifocal and osteoblastic lesions involving the axial skeleton and non-calcified lymph nodes in the pelvic and lumbar aortic groups. Most adenocarcinomas are capable of producing macrocalcification. We report a case of prostate cancer with de novo calcified metastases to the liver and retroperitoneal lymph nodes mimicking the pattern usually seen in mucin-producing adenocarcinomas arising from the gastrointestinal tract. To our knowledge, this is the first such case to be reported in the literature. We propose a multifactorial mechanism that supports dystrophic calcification in this case. The knowledge of atypical presentation of metastatic disease can prevent diagnostic delay and prompt initiation of therapy.

Metastatic tumors to the ovaries: a study of 170 cases in northern Thailand

The cases of malignant ovarian tumors treated at Chiang Mai University hospital between 1992 and 2003 were histologically reviewed. The medical records, the radiologic findings, and the follow-up outcome in the cases suspicious or diagnostic of metastases were reviewed to confirm the diagnosis and to determine the primary sites. Metastatic tumors accounted for 30% of malignant ovarian tumors. A total of 170 cases of metastatic tumors included 117 cases with nongynecologic origin and 53 cases with gynecologic origin. Nongynecologic metastatic tumors were from large intestine (31%), stomach (14%), intrahepatic bile duct (10%), breast (9%), extrahepatic bile duct/gallbladder (7%), appendix (5%), hematologic tumors (3%), others (4%), and unknown primary site (16%). Metastatic gynecologic tumors were from cervix (53%), corpus (34%), fallopian tube (11%), and gestational trophoblastic disease (2%). The proportion of metastatic tumors to malignant ovarian tumors in northern Thailand was comparable to those of the Western or Japanese studies. However, the distribution of the primary sites was different and was correlated with the cancer incidence in Thai women. The majority of mucin-producing adenocarcinomas involving the ovaries were metastatic tumors.

Acute Cerebral Infarction during Combination Chemotherapy with S-1 and Cisplatin for a Young Patient with a Mucin-Producing Adenocarcinoma of the Stomach

We report a 29-year-old woman with gastric cancer who developed Trousseau's syndrome, a malignancy-related thromboembolism, during chemotherapy. She was diagnosed with a mucin-producing adenocarcinoma of the stomach, and chemotherapy with S-1 and cisplatin was commenced. During treatment, she developed a sudden onset of right hemiplegia. Magnetic resonance imaging showed an acute cerebral infarction of the left cerebral hemisphere. The underlying pathophysiology is thought to be chronic disseminated intravascular coagulation due to mucin-producing adenocarcinomas. However, cisplatin-induced vascular toxicity and hypercoagulability caused by decreased plasma protein C activity, elevated plasma von-Willebrand factor levels, and hypomagnesemia has also been proposed to be associated with thrombogenicity.