Granulosa cell tumor and mucinous cystadenoma arising in a mature cystic teratoma of the ovary: A unique case report and review of literature

Mature cystic teratoma of the ovary, though it contains derivatives of all three embryonic germ cell layers, rarely presents together with ovarian epithelial or sex cord-stromal tumors. Only a few cases of ovarian cystic teratoma in association with granulosa cell tumor have been reported in the literature, and simultaneous occurrence of mucinous cystadenoma and granulosa cell tumor is even rarer. To our knowledge, there has never been a report of mature cystic teratoma of ovary coexisting with granulosa cell tumor and mucinous cystadenoma. We report a case of mature cystic teratoma, mucinous cystadenoma, and granulosa cell tumor in the ovary of a 40-year-old woman. The involved ovary, massively enlarged by a multiloculated cyst, showed a hair-sprouting mass with a yellow-tan nodule embedded in the cyst wall. Microscopically, three tumor types were revealed: mature cystic teratoma, mucinous cystadenoma, and granulosa cell tumor.     

Intestinal adenocarcinoma arising in a mature cystic teratoma of the ovary: a case report

Gastrointestinal adenocarcinoma arising in mature cystic teratomas of the ovary is extremely rare. We report a case of well-differentiated intestinal adenocarcinoma arising in a mature cystic teratoma of the ovary in a 77-year-old woman, presenting as acute abdomen with ovarian torsion. An immunohistochemical study revealed expression of CK20 and CK7, and the tumor was also positive for MUC2. The patient had no evidence of disease after 12 months of follow-up.     

Adenocarcinoma arising from mature cystic teratoma of the ovary

An extremely rare adenocarcinoma arising from a mature cystic teratoma is reported. A 58-year-old woman underwent bilateral salpingo-oophorectomy because of a tumor in each ovary. The right ovarian tumor (solid, 9.6 × 9.6 × 6.3 cm) was a benign thecoma. Histology revealed the left ovarian cystic tumor (multilocular, 6.4 × 4.8 × 2.8 cm) was a mature cystic teratoma containing skin, fatty tissue and respiratory epithelial tissue. In addition, there was a small focal adenocarcinomatous lesion contiguous to the teratomatous ciliated columnar epithelium without stromal invasion (so-called adenocarcinoma in situ ) that was suggestive of respiratory epithelium origin. However, goblet cells were present in the glandular structures of the lesion and immunohistochemical staining was segmentally strongly positive for CK20 and uniformly negative for CK7. These results suggested that the adenocarcinomatous lesion had a mucin secretory gastrointestinal phenotype. Further investigation and the collection of more cases is necessary to determine the origin and growth mechanism of adenocarcinoma arising from mature cystic teratoma of the ovary.     

Intratesticular mucinous cystadenoma: immunohistochemical comparison with ovarian and colonic tissue

We report a case of a primary intratesticular mucinous cystadenoma in an asymptomatic 39-year-old man. The mass was found incidentally during a consultation for infertility. Pathologic examination of the orchiectomy specimen revealed a unilocular cyst lined with bland mucinous epithelium and mucinous extravasation, consistent with a diagnosis of mucinous cystadenoma. Foci of bone were also found in association with extensive chronic inflammation. Immunohistochemical stains performed showed immunoreactivity for cytokeratin 7, and nonreactivity for cytokeratin 20, CA125, chromogranin, and synaptophysin. The immunohistochemical staining patterns of the present case are compared with those of known mucinous cystadenomas of the ovary and nonneoplastic colonic mucosa. The histogenesis of this entity is discussed in light of the literature and the immunohistochemical findings in this rare case.     

Bowel loop in an ovarian tumor: Grossly visible, completely developed intestinal loop in mature cystic teratoma of malignant mixed germ cell tumor

Although a gastrointestinal-type epithelium is observed in 7–13% of mature cystic teratoma cases, the occurrence of a grossly visible, organized gastrointestinal loop formation is very rare. Presented here is the case of a 14-year-old girl with malignant mixed germ cell tumor in the ovaries. In her left ovary a grossly visible, intestinal loop, 9 cm long, with hanging mesentery attached to the cystic wall of a mature cystic teratoma associated with a yolk sac tumor was observed, and in her right ovary another mature cystic teratoma was observed. Microscopy of the intestinal loop indicated a well-organized, intact layer of small intestinal wall. The yolk sac tumor predominantly had a polyvitelline pattern. Previously, gastrointestinal wall or epithelium that was identified on microscopy has been reported. To the authors' knowledge this is the first case report of the formation of a grossly visible, completely developed intestinal loop in a malignant mixed germ cell tumor.     

Malignant transformation of ovarian mature cystic teratoma with a predominant pulmonary type small cell carcinoma component

A 68-year-old woman was diagnosed with mature cystic teratoma of the left ovary when she was 44 years old. The tumor recently enlarged rapidly, and abdominal magnetic resonance imaging revealed an intrapelvic cystic lesion, which measured 123 × 120 × 107 mm and contained a mural nodule. Under a clinical diagnosis of malignant transformation of mature cystic teratoma, bilateral salpingo-oophorectomy with total hysterectomy and omentectomy were performed. The resected specimen showed a unilocular cystic lesion containing a well-demarcated mural nodule measuring 35 × 30 × 25 mm in the left ovary. A microscopic examination revealed various types of carcinoma in the mural nodule: pulmonary type small cell carcinoma (65%), adenocarcinoma (25%), squamous cell carcinoma (5%), and transitional cell carcinoma (5%). Small cell carcinoma was positive for CD56, synaptophysin, and chromogranin A. The adenocarcinoma component showed intestinal phenotypes; i.e. cytokeratin (CK) 7(-), CK20(+), CDX2(+), estrogen receptor(-), and progesterone receptor (-). Interestingly, CDX2 positivity was retained in all of the carcinomas. It was assumed that the adenocarcinoma had arisen from an intestinal epithelium in the mature cystic teratoma and then differentiated into the diverse histological types mentioned above.     

Primary squamous carcinoma of the ovary likely arising from a monodermal cystic mucinous teratoma

We present a 58-year-old woman with primary squamous carcinoma of the ovary likely arising from a monodermal cystic mucinous teratoma. Noninvolved ovary showed no Brenner tumor, endometriosis, transitional carcinoma, endometrioid adenocarcinoma, or typical multigerm layer classic mature teratoma. Moreover, no other primary site was possible because there were no prior or concomitant squamous carcinomas, or history of cervical intraepithelial neoplasia. The tumor showed strong positivity for p63 and CK5/6, reactivity that also extended from the squamous carcinoma into the basal-cell lining of the mucinous cyst of a likely monodermal teratoma. This basal-cell pattern was absent in a series of conventional benign and borderline cystic mucinous cystadenomas of the ovary, but clearly present in the mucinous cysts part of mature teratomas. We present this as a unique case of squamous carcinoma likely arising from a monodermal cystic mucinous teratoma. Moreover, we submit that the p63 and CK5/6 staining pattern may help to differentiate monodermal cystic mucinous teratoma from conventional cystic mucinous tumors.     

KRAS mutation positive mucinous adenocarcinoma originating in mature ovarian teratoma: Case report and review of literature

Mature ovarian teratomas rarely undergo transformation into malignancy. Carcinomas, mostly squamous cell carcinoma, are the most common malignancy arising in mature cystic teratoma. In the present report we describe a 13‐year‐old girl who developed a large mass in her ovary. Fine needle biopsy identified intestinal type mucinous adenocarcinoma, which was also identified in the full surgical specimen. Extensive sampling of the surgical specimen also identified areas of mature cystic teratoma. Interestingly, molecular analysis of DNA extracted from various components of the lesion identified KRAS mutation in the carcinoma, borderline mucinous tumor and benign intestinal‐type epithelium but not in the epidermal component of the teratoma. To the best of our knowledge this is the first report of KRAS mutation in mucinous carcinoma originating in mature cystic teratoma. We discuss the importance of extensive tissue sampling to differentiate between carcinoma originating in teratoma and metastatic colorectal carcinoma to the ovary. Additionally, the identification of KRAS mutation in the morphologically benign intestinal‐type epithelium indicated that it is an early event in the carcinogenic sequence and that the molecular pathway of carcinogenesis in teratoma is similar to that in the carcinogenic process of somatic tissue.     

Adenocarcinoma with sarcomatous dedifferentiation arising from mature cystic teratoma of the anterior mediastinum

Mediastinal teratoma with malignant transformation (TMT) is a very rare condition. A 44-year-old man presented with a large cystic mass of the anterior mediastinum. The tumor was surgically removed. The cystic mass was well demarcated, with an irregularly thickened wall. Histologically, the cystic wall was mainly lined by non-ciliated columnar epithelium and focally by squamous epithelium. A nodular part of the cystic wall revealed well-differentiated adenocarcinoma composed of tubulopapillary structures. Deep in the nodular tissue, neoplastic glands merged into undifferentiated sarcomatous cells. Immunohistochemically, CK7, CK19, and smad-4 were strongly and diffusely positive in adenocarcinoma. CD10 was focally positive on the luminal surface of the glands, and MUC5AC was also focally positive. TTF-1, cdx-2, and CK20 were negative in the adenocarinoma. Sarcomatous area showed diffuse strong positivity for vimentin, but was negative for the aforementioned epithelial markers. About 10 months postoperatively, a left pleural effusion had developed with multiple pleural nodules on computed tomography scan of the chest. The cytologic diagnosis from pleural fluid was metastatic adenocarcinoma. To our knowledge, in the English literature, this is the first case of adenocarcinoma with sarcomatous transformation that has developed in a mature cystic teratoma of the mediastinum and shows pleural metastasis.     

Mucinous cystadenoma coexisting with stromal tumor with minor sex-cord elements of the ovary: a case report

Mucinous neoplasms occur rarely in association with cystic teratoma, Sertoli-Leydig cell tumor, granulosa cell tumor or carcinoid tumor. Several cases of an ovarian stromal tumor with minor sex-cord elements have been reported in the literatures. However, there has been no report about an ovarian mucinous neoplasm coexisting with a stromal tumor with sex-cord elements yet. We report a case of an ovarian neoplasm composed of both mucinous cystadenoma and stromal tumor with minor sex-cord elements in a 58-yr-old female. The ovary including the mass measured 5 cm in size. On section, it revealed an unilocular cyst (4.5 cm in diameter) filled with mucinous fluid. There was a round, yellow, solid nodule, 1.5 cm in diameter within the wall. Microscopically, the cyst was lined by a single layer of endocervical mucinous epithelium and the nodule was composed of spindle cells showing an intersecting and whorled arrangement. There were cell nests showing polygonal shape with abundant cytoplasm among the spindle cells. They showed immunoreactivity for inhibin and did not have any connection with the adjacent mucinous epithelium. Therefore, we interpret the mucinous cystadenoma as having arisen de novo.     

Urachal adenocarcinoma metastatic to the ovaries resembling primary ovarian mucinous carcinoma: a case report with the immunohistochemical study

Urachal adencarcinoma is rare and its metastasis to the ovary is extremely rare. I report here on a case of urachal adenocarcinoma that metastasized to bilateral ovaries in a 72-year-old female. She presented with vaginal spotting. Abdominal CT revealed a huge multiloculated cystic mass in the recto-uterine pouch and a solid mass with dot calcification in the anterior pelvic cavity. The resected ovaries were equal-sized at about 10cm at the greatest diameter. The sectioned surfaces were predominantly multicystic with a solid nodule. Microscopically, both ovaries were mainly composed of cystic glands lined by mucin-containing epithelium with atypical nuclei. The solid nodule consisted of irregularly infiltrating glands and single tumor cells. Two years later, the patient was admitted with hema-turia. The kidney CT revealed a solid mass with calcification in the bladder dome, which suggested urachal carcinoma. The partial cystectomy specimen revealed an ill-defined ulcerative tumor. Histologically, the tumor corresponded to mucinous adenocarcinoma and centered at the bladder wall with predominant invasion of the muscularis. The immunohistochemical profiles of the ovarian and urachal tumors were exactly the same. The tumor cells were diffusely positive for CK20, CDX-2, MUC2 and MUC5AC, focally positive for 34(3E12 and negative for CK7.     

Urachal adenocarcinoma metastatic to the ovaries resembling primary ovarian mucinous carcinoma: a case report with the immunohistochemical study

Urachal adencarcinoma is rare and its metastasis to the ovary is extremely rare. I report here on a case of urachal adenocarcinoma that metastasized to bilateral ovaries in a 72-year-old female. She presented with vaginal spotting. Abdominal CT revealed a huge multiloculated cystic mass in the recto-uterine pouch and a solid mass with dot calcification in the anterior pelvic cavity. The resected ovaries were equal-sized at about 10cm at the greatest diameter. The sectioned surfaces were predominantly multicystic with a solid nodule. Microscopically, both ovaries were mainly composed of cystic glands lined by mucin-containing epithelium with atypical nuclei. The solid nodule consisted of irregularly infiltrating glands and single tumor cells. Two years later, the patient was admitted with hema-turia. The kidney CT revealed a solid mass with calcification in the bladder dome, which suggested urachal carcinoma. The partial cystectomy specimen revealed an ill-defined ulcerative tumor. Histologically, the tumor corresponded to mucinous adenocarcinoma and centered at the bladder wall with predominant invasion of the muscularis. The immunohistochemical profiles of the ovarian and urachal tumors were exactly the same. The tumor cells were diffusely positive for CK20, CDX-2, MUC2 and MUC5AC, focally positive for 34(3E12 and negative for CK7.     

Histogenetic considerations on mucinous cystomas of the ovary based on histochemical and immunohistochemical findings

Mucinous cystomas of the ovary, according to a new proposed classification (I.A.P., Dublin 1988), are classified in three types: endocervical, intestinal and mixed. Their histogenesis is still controversial, thus requiring further investigations. There are two main theories on this matter: a teratomatous theory based on the assumption that the mucinous cystoma is allegedly a teratoma having a monophyletic development where only the endodermal gastrointestinal component remains. The second theory, currently the most widely accepted one, maintains that mucinous cystomas derive from Muller duct residues or, more generally, from introflections of the coelomic epithelial lining through a Muller-type metaplastic process. Some authors also accept both theories. A group of 117 mucinous cystomas were investigated by histochemical methods (PB/KOH/PAS; PAT/KOH/Bh/PAS), to demonstrate the presence of O-acetylated sialomucin variants in goblet cells of intestinal type component. Endocervical type mucinous cystomas have always presented as PB/KOH/PAS negative, whereas mixed type mucinous cystomas presented as positive according to the following percentage: benign forms, 31%; borderline, 67%; malignant, 50%. These data should confirm the hypothesis that intestinal type cystomas may derive from the surface coelomic epithelium of the ovary, through a gastrointestinal metaplastic process. This hypothesis is further supported by the data obtained from the observation on two cases of intestinal metaplasia of endocervical glands, kindly supplied by Dr. Trowell. In one of them, a weak O-acetylated sialomucin secretion was identified, in addition to the presence of argentaffin cells. Furthermore, out of 38 adenocarcinomas of the endometrium and 15 adenocarcinomas of the endocervix, one case of endocervical adenocarcinoma was found, characterized by a mucous secretion rich in O-acetylated sialomucins. Moreover, immunohistochemically, by means of anti-chromogranin A monoclonal antibodies, endocrine cells were found in benign, borderline and malignant mucinous cystomas of mixed type. These data do not seem to confirm the assumed correlation between neuroendocrine cell presence and biologic behaviour of the neoplasm nor do they clarify tumor histogenesis. Another immunohistochemical study with BD5 monoclonal antibody demonstrated that this marker was present in the intestinal type epithelium of mixed mucinous cystomas. The histogenetic teratomatous hypothesis of ovarian mucinous cystomas was confirmed by reviewing 100 ovarian teratomas, in which O-acetylated sialomucins were found in the epithelial component of one mucinous carcinoid and in the intestinal type epithelium of 9 mature cystic teratomas.(ABSTRACT TRUNCATED AT 400 WORDS)     

Expression pattern of CK7, CK20, CDX-2, and villin in intestinal-type sinonasal adenocarcinoma

BACKGROUND: Intestinal-type sinonasal adenocarcinoma (ITAC) is an uncommon neoplasm, which resembles adenocarcinoma of the gastrointestinal tract. ITAC occurs sporadically or in association with occupational exposure to hardwood dust and other agents. AIMS: To investigate the phenotype and possible pathogenetic mechanisms of primary sinonasal and nasopharyngeal adenocarcinomas by staining for cytokeratin 7 (CK7), CK20, CDX-2, and villin. METHODS: Twelve sporadic sinonasal and nasopharyngeal adenocarcinomas were stained with monoclonal antibodies to CK7, CK20, CDX-2, and villin. The ITACs were classified as papillary, colonic, solid, mixed, or mucinous types. RESULTS: The diagnosis of ITAC was confirmed in 10 cases: five were colonic type and five were papillary. One was a sinonasal papillary low grade adenocarcinoma, and one a papillary nasopharyngeal adenocarcinoma, and these tumours were CK7 positive, but CK20, CDX-2, and villin negative. All ITACs were positive for CK20, CDX-2, and villin, and six were CK7 positive. One ITAC had a focus of intestinal metaplasia away from the invasive carcinoma. CONCLUSIONS: Sinonasal ITACs have a distinctive phenotype, with all cases expressing CK20, CDX-2, and villin. Most ITACs also express CK7, although a proportion of tumours are CK7 negative. ITAC seems to be preceded by intestinal metaplasia of the respiratory mucosa, which is accompanied by a switch to an intestinal phenotype. Although ITACs are morphologically similar, differences in cytokeratin expression patterns suggest two distinct types. The expression pattern of CK7, CK20, CDX-2, and villin positive may be useful in separating these tumours from other non-ITAC adenocarcinomas of the sinonasal tract and nasopharynx.     

Expression of cytokeratin 20 in mucinous bronchioloalveolar carcinoma

Mucinous bronchioloalveolar carcinomas (BACs) can closely mimic metastatic adenocarcinoma to the lung both clinically and morphologically. Several studies have demonstrated that the differential expression of cytokeratin 7 (CK7) and cytokeratin 20 (CK20) is a valuable diagnostic tool in differentiating primary pulmonary adenocarcinomas (PPAs) (usually CK7 positive/CK20 negative) from metastatic colonic adenocarcinoma (usually CK7 negative/CK20 positive). The present study is designed to correlate the histologic subtypes of PPA with expression of 7 and 20. A total of 113 cases of bonafide PPA were selected and classified according to the 1999 World Health Organization criteria as adenocarcinoma, NOS (n = 80), nonmucinous BAC (n = 14), and mucinous BAC (n = 19). Representive sections of all the tumors were immunohistochemically analyzed for CK7 and CK20 expression. To evaluate the diagnostic utility of CK7 and CK20 expression, 6 cases of colonic adenocarcinoma metastatic to the lung were tested with the same antibodies and compared with mucinous BAC. Results were expressed in a semiquantitative fashion based on the percentage of positive tumor cells: <10%, focal; 10% to 25%, 1+; 26% to 75%, 2+; > or =76%, 3+. All 113 PPAs exhibited strong, diffuse CK7 expression. With respect to CK20 expression, 17 of the 19 cases (89.4%) of mucinous BAC showed moderate to strong expression of this protein, whereas only 10 cases of conventional adenocarcinomas and 4 cases of nonmucinous BAC exhibited expression. All 6 examples of metastatic colonic adenocarcinomas were negative for CK7 and strongly positive for CK20. In summary, mucinous BAC is distinct from other PPAs by virtue of its CK20 expression. Although the CK7/CK20 immunoprofile is a valuable diagnostic marker for differentiating primary lung adenocarcinoma from metastatic colonic adenocarcinoma, caution should be exercised when dealing with mucinous BAC.     

Meningioma in mature cystic teratoma of the ovary

A case of meningioma arising in a mature cystic teratoma of the ovary in a 60-year-old woman is described. The tumor was located in the right ovary, and salpingo-oophorectomy was performed. The right ovary was 10 x 10 x 8 cm in size and contained an unilocular cyst. In the wall, a solid nodule measuring 3 x 3 x 2 cm was noted. Histologically, the cyst wall was composed of typical mature cystic teratoma. In contrast, the mural nodule was composed of the proliferating spindle- and polygonal-shaped cells showing positive staining for epithelial membrane antigen and microcystic change was prominent. These findings were consistent with microcystic meningioma. The arachnoidal cells around mature brain tissue may be the origin of this unusual tumor. To the best of our knowledge, this is the first case of mature cystic teratoma with meningioma of the ovary reported in English medical literature. This case may further indicate the totipotential nature of mature cystic teratoma.     

Mature cystic teratoma of the ovary with a small ganglioneuroma

A case of ganglioneuroma arising within a cystic mature teratoma of the ovary in a 34-year-old woman is reported. Patient underwent right adnexectomy. The ovary was completely replaced by a bilocular cystic lesion, measuring 8 cm in diameter and filled with adipose tissue and pilosebaceous material. Microscopically the cyst was composed by a mature cystic teratoma containing skin with dermal appendages, fatty tissue and bronchial epithelium. Furthermore a nodule (0.5 cm in size) composed of mature ganglion cells, axons and Schwann cells, was identified. Ganglion cells were positive for NSE and synaptophysin, while Schwann cells stained positively with S100 protein and GFAP. To the best of our knowledgment this is the first reported cases of ganglioneuroma arisen within a cystic mature teratoma of the ovary.     

Ovarian mucinous cystadenoma with mural nodule of anaplastic carcinoma.

The occurrence of malignant mural nodule in benign cystic common epithelial tumor of the ovary have been reported in only three cases; the case one was mucinous cystadenoma with a mural nodule of fibrosarcoma and the others were of carcinomas. Our case was another rare case of ovarian mucinous cystadenoma with mural nodule of anaplastic carcinoma in a 42-year-old woman. The cystadenoma had an unilocular cystic cavity and a mural nodule with thick multinodular solid wall. The internal cystic wall was lined with mucinous cystadenoma without any malignant features. The mural nodule showed anaplastic carcinomatous differentiation and its nature was confirmed by immunohistochemistry and electron microscopy. This tumor had metastasized to the right salpinx, uterus, cul-de-sac, periureter and mesentery.     

Expression of cytokeratins 7 and 20 in ovarian neoplasia

To further delineate specific staining patterns and refine the differential usefulness of cytokeratin (CK) 7/20 staining, we studied multiple ovarian tumors and primary nongynecologic neoplasms likely to metastasize to the ovary. Immunohistochemical analysis with semiquantitative grading to give quartile scores (0-4) was performed on 127 cases. Subsequent analysis indicated that a more informative diagnostic segregation could be achieved with a biphasic grading system (>50% staining, positive; 50% or less, negative). Lower intestinal tumors were CK7- and usually CK20+, while upper gastrointestinal tumors, including those of pancreatobiliary origin, were mostly CK7+ and CK20-. Serous papillary ovarian tumors were all CK7+ and CK20-. Mucinous ovarian carcinomas were all CK7+ and slightly more often CK20-, whereas the small number of ovarian borderline mucinous tumors studied were the most problematic, with no clear pattern. Multiple different tumor types from all nonovarian gynecologic sites were fairly consistently CK7+ and almost always CK20-. Differential CK staining of mucinous tumors of the female genital tract using CK7 and CK20 is useful for predicting the site of origin, provided samples are adequate in size. The most specific usefulness is the identification of lower gastrointestinal vs "other" neoplasms.