RAS Mutation-Positive Follicular Variant of Papillary Thyroid Carcinoma Arising in a Struma Ovarii

Struma ovarii is an ovarian mature teratoma composed exclusively or predominantly of thyroid tissue. Malignant transformation of struma ovarii is rare and poorly understood, although this process is thought to be similar to carcinogenesis in malignant tumors of differentiated thyroid tissue originating in the thyroid gland. Genetic alterations in the mitogen-activated protein kinase pathway, including mutations of BRAF, RAS, and RET genes, have been implicated in the development of differentiated thyroid carcinoma arising in the thyroid gland. We report here a case with RAS mutation detected in a malignant struma ovarii. The patient is a 38-year-old female who had a 2.4 cm ovarian cyst noted incidentally on a first trimester ultrasound. She proceeded to ovarian cystectomy post-delivery, with pathologic examination detecting a papillary thyroid carcinoma, follicular variant, arising in a cystic teratoma. The tumor was tested for BRAF, RAS, and RET/PTC mutations. HRAS codon 61 mutation was identified. This is the first report of RAS mutation detected in the follicular variant of papillary carcinoma arising in a struma ovarii. It provides evidence that tumors developing in this setting involve molecular mechanisms similar to those implicated in tumors developing in the thyroid gland.     

Ovarian cystic tumor composed of Brenner tumor and struma ovarii

Ovarian tumor composed only of Brenner tumor and struma ovarii is very rare; only 6 cases have been reported in the English literature, to the best of the author's knowledge. A 66-year-old woman underwent right oophorectomy because of torsion of right ovarian cyst. Macroscopically, the ovarian cyst was hemorrhagic and red. Cystic content was hemorrhagic fluid. Microscopically, the cyst walls were composed only of Brenner tumor (50% in area) and struma ovarii (50% in area). Hemorrhage and ischemic changes were seen. Other elements were not recognized. No malignant transformation was noted. These two elements were separately present, and no mergers between them were recognized. Immunohistochemically, the Brenner tumor element was positive for cytokeratins (AE1/3 and CAM5.2) and Ki67 (labeling=3%), but negative for thyroglobulin, TTF-1, p53, CA125, and vimentin. The struma ovarii element was positive for cytokeratins (AE1/3 and CAM5.2), thyroglobulin, TTF-1 and Ki67 (labeling=5%), but negative for p53, CA125 and vimentin. The findings suggests that there were cases of ovarian cyst composed only of Brenner tumor and struma ovarii, that such a case may be monodermal mature cystic teratoma or the Brenner tumor element was derived from surface epithelium in the preexisting struma ovarii, and that such a tumor manifest as cystic torsion.     

Highly differentiated follicular carcinoma of ovary: Use of imprint cytology at intraoperative consultation

Highly differentiated follicular carcinoma of ovary (HDFCO) is a rare entity known to arise in struma ovarii. Clinical presentation and radiological features mimic other cystic ovarian neoplasm. Thus, intraoperative diagnosis of this entity can be challenging. We hereby report a HDFCO case of a 52‐year‐old woman, who presented with significant abdominal bloating for 3 months. Imaging showed a 11.7 cm left adnexal‐mixed cystic and solid mass, adhering to the bowel with ascites. The mass was examined intraoperatively and showed multilocular cysts filled with straw or red brown‐colored gelatinous fluid. Microscopically, the tumor consisted of small and large follicles with proteinous material and bland‐looking cuboidal cells, suspicious for struma ovarii or granulosa cell tumor with extensive cystic changes, while imprint cytology slides showed watery colloid with cracking artifact favoring the former. However, the adherence to the bowel suggested HDFCO, and prompted surgical staging. The histology of the ovarian mass in the permanent section resembled goiterous thyroid tissue with invasion of endocervical stroma, uterine wall and colonic serosa, and presence of tumor nodules in omentum leading to the diagnosis of HDFCO. Due to striking resemblance of HDFCO to benign thyroid goiter, searching for invasive and metastatic foci is crucial for correct diagnosis. In addition, intraoperative imprint cytology revealing colloid with cracking artifact is helpful for differentiating struma ovarii and/or HDFCO from other ovarian lesions.     

Coexisting Brenner tumor and struma ovarii in the right ovary: case report and review of the literature

A bilateral ovarian tumor composed of mixed Brenner tumor and struma ovarii in the right ovary and mature cystic teratoma in the left ovary, is described. Mixed Brenner tumor and struma ovarii is rare; eight cases are reviewed. In this case, in addition to the typical Brenner tumor and struma ovarii, some nests composed of both Brenner tumor and struma ovarii in one nest were found in the right ovarian tumor. Immunohistochemically, the struma ovarii is stained for thyroglobulin, and Brenner nests showed various degrees of positive stain for thyroglobulin, which is a specific finding. Brenner tumor, in this case, may produce thyroglobulin or have a receptor to thyroglobulin or analog of thyroglobulin. The origin of mixed Brenner tumor and struma ovarii may be germ cell, as described in some literature, or the Brenner tumor may be of a metaplastic nature, although the Brenner tumor is fourfold the size of struma ovarii in the case presented.     

Solitary luteinized follicle cyst of pregnancy and puerperium

We report a huge ovarian solitary luteinized follicle cyst (SLFC) that contained 17 liters of fluid. Computed tomography scan revealed a 32 x 32 x 20 cm right simple cystic ovarian mass without calcification or septation. The fluid was removed, and the collapsed unilocular cyst was examined pathologically. No solid or papillary areas were identified. The cyst wall lining was composed of multiple layers of luteinized cells of variable size and shape with abundant eosinophilic cytoplasm and focally enlarged, pleomorphic, and hyperchromatic nuclei. Nests of luteinized cells were embedded within the fibrous tissue of the cyst wall. These findings are characteristic of solitary luteinized follicle cyst of pregnancy. Even though less than 15 cysts of this kind have been recorded, one should consider this uncommon, benign, non-neoplastic cystic ovarian lesion in the differential diagnosis of other cystic ovarian lesions.     

Imprint cytology of strumal carcinoid of the ovary: A case report with immunocytochemical analysis

Strumal carcinoid is a rare ovarian tumor defined as carcinoid associated with struma ovarii. We report here the second cytological case of strumal carcinoid and performed immunocytochemical analysis for the first time. A 68‐year‐old Japanese female was found to have a solid tumor with small cystic components in the left ovary, and bilateral salpingo‐oophorectomy was performed. The Papanicolaou smear of the imprint cytological specimen of the left ovarian tumor revealed presence of two distinct components. The first component included thyroid follicles, which was composed of flat sheets of polygonal epithelial cells without nuclear groove and intranuclear inclusion. The other component was composed of trabecular clusters of columnar cells containing round to slender nuclei with “salt and pepper” chromatin. Immunocytochemical analysis revealed that synaptophysin was expressed in the latter component. Therefore, a cytodiagnosis of strumal carcinoid was made. Histopathological analyses confirmed the diagnosis of strumal carcinoid. Albeit rare, carcinoid tumor occurs in the ovary, and the recognition of characteristic nuclear features and cellular arrangement leads to correct cytodiagnosis. Presence of struma ovarii component suggests an ovarian origin. Moreover, immunocytochemical analysis for neuroendocrine markers aids its differential diagnosis from granulosa cell tumor and carcinoma arising from struma ovarii.     

Retroperitoneal lymphangioleiomyomatosis associated with endosalpingiosis

A case of retroperitoneal lymphangioleiomyomatosis (LAM) arising from endosalpingiosis is described. A 25-year-old woman with no history of tuberous sclerosis or hormonal therapy presented with a painless, palpable abdominal mass. Computed tomographic and magnetic resonance imaging studies of the abdomen demonstrated a 4 cm cystic mass in the retroperitoneum. Macroscopically, the excised retroperitoneal cyst was multilocular and measured 4.0 x 3.5 x 3.5 cm. Histologically, the lesion demonstrated three components. The first comprised multiple cysts or glands lined by columnar epithelial cells with cilia. The second component was a condensation of small stromal cells immediately subjacent to the cystic epithelium or glands. The third component was a thick exterior wall composed of plump spindle cells with clear to palely eosinophilic cytoplasm in a fascicular pattern, and slit-like vascular spaces, resembling LAM. Immunohistochemically, the epithelium and glands were positive for cytokeratin 7. The stromal cells were positive for vimentin and CD10. The cells of the LMA-like component showed positive staining for HMB45, alpha-smooth muscle actin, muscle actin and h-caldesmon. The lesion, LAM arising from endosalpingiosis, represents a distinctive pathologic entity that should be recognized and studied further. This type of lesion should be included in the differential diagnosis of retroperitoneal cystic lesions.     

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.     

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.     

Unilateral malignant struma ovarii in a case of bilateral ovarian teratoma with raised CA-125 level: a rare case with treatment dilemmas

Struma ovarii are specialized form of mature ovarian teratoma comprised predominantly of thyroid tissue (>50%). Most of the struma ovarii are benign; rarely can they undergo malignant transformation. Elevated CA-125 levels with benign struma ovarii have been seen in only 5 cases in literature. The association of malignant struma ovarii and high CA-125 levels with pseudo-Meig syndrome has been reported in only 2 cases in English literature. We describe a case of a 46-year-old multigravida who presented with an abdominal mass and raised CA-125 levels. Radiological investigations revealed bilateral cystic adnexal masses with ossified elements on left side suggesting a teratoma. Intraoperative frozen section and final pathology revealed bilateral teratoma with follicular variant of papillary thyroid carcinoma arising in the left ovary. To the best of our knowledge, this is the first case of malignant struma ovarii in combination with bilateral teratoma. The dilemmas related to preoperative diagnoses with elevated CA-125 levels, mimicking an epithelial ovarian neoplasm; intraoperative frozen section consultation; management and follow-up issues in this rare malignancy are discussed.     

Malignant ovarian struma

A rare observation of an unilateral ovarian tumour in a 62-year-old patient is presented. According to the clinical data and the results of the ultrasound examination the tumour was considered as a carcinoma. Hysterectomy with appendages and large omentum resection were performed. A tumour of the right ovary, 13 x 10 x 10 cm was found: cyst with a grey-brown soft node was observed in the cut surface. Histologically, the struma remnants were observed in the cyst wall and structures corresponding to the follicular carcinoma of the thyroid, the central parts of which had a structure of the C-cell thyroid carcinoma. Ultrastructural examination confirmed a light microscopic diagnosis of the malignant monodermal ovarian teratoma developing from the struma with areas of follicular solid C-cell carcinoma.     

Foregut duplication cyst of the stomach with pseudostratified columnar ciliated epithelium

Duplication cyst of the stomach with pseudostratified columnar ciliated epithelium is extremely rare. A 72-year-old Japanese woman visited Oomoto Hospital for examination of the stomach. Gastroendoscopy indicated a slightly depressed gastric cancer in the anterior wall of the middle third of the stomach. Adenocarcinoma was confirmed on endoscopic biopsy. Preoperative CT indicated a subserosal cystic lesion 2 cm in diameter on the lesser curvature of the stomach. The cystic lesion was resected through distal gastrectomy and systematic lymph node dissection. Histopathology showed that the cyst did not communicate with the gastric lumen, had pseudostratified columnar ciliated epithelium with circular muscle layers, and did not have gastric epithelium or cartilaginous tissue. The gastric cancer consisted of moderately differentiated adenocarcinoma with submucosal invasion and lymph node metastasis. Consequently, the present patient was diagnosed as having foregut duplication cyst of the stomach.     

Hepatoid carcinoma of the pancreas penetrating into the gastric cavity: a case report and literature review

A 79-year-old Japanese woman was admitted to our hospital for treatment of a pancreatic tumor measuring approximately 7 × 5 cm. The tumor had invaded the left adrenal gland and gastric wall and had penetrated into the gastric cavity. Surgical resection was performed. The tumor was composed of a brown to whitish solid area and a zone of hemorrhage, necrosis, and cystic degeneration resembling the gross features of solid pseudopapillary tumor (SPT). Histologically, the tumor showed a heterogeneous growth pattern with a combination of seat-like, trabecular, papillary and hemorrhagic-necrotic areas in various proportions. The differential diagnoses first considered were acinar cell carcinoma, neuroendocrine carcinoma and SPT with malignant transformation. Immunohistochemistry showed tumor cells were negative for pancreatic exocrine enzymes and endocrine markers. Tumor cells diffusely expressed cytokeratin 19, alpha-fetoprotein, carcinoembryonic antigen and glypican-3, but lacked vimentin or β-catenin expression. Small proportions of tumor cells expressed hepatocyte paraffin-1. Although typical morphological features of well-differentiated hepatocellular carcinoma (HCC) were not distinctly apparent, the tumor morphology partly resembled poorly differentiated HCC. Given these findings and considerations, the tumor was finally diagnosed as poorly differentiated hepatoid carcinoma of the pancreas.     

Coexistence of mature teratoma and thecoma in an ovary. A report of two cases.

Two cases of coexisting mature teratoma and thecoma are reported. In Case 1, a 36-year-old woman presented with severe genital bleeding and an ovarian tumor, 12 x 9 cm in size, was found. In Case 2, a 48-year-old postmenopausal woman presented with severe lower abdominal pain and an ovarian tumor, 15 x 11 cm in size, was detected. Macroscopically, the resected tumors of both cases showed a unilocular cystic tumor adjacent to a solid tumor. Microscopically, the cystic tumors were composed of cutaneous tissues and the solid tumors consisted of spindle cells with lipid-rich cytoplasm, arranged in interlacing bundles. The cystic tumor and the solid tumor were completely separate and no transitional features were recognized histologically.     

Mucinous adenocarcinoma arising in a giant urachal cyst associated with pseudomyxoma peritonei and stromal osseous metaplasia

An unusual urachal lesion, which Is a muclnous adenocarcinoma arising in a giant urachal cyst and is associated with pseudomyxoma peritonei and stromal osseous metaplasia of the cyst wall, was examlned in a 45-year-old male. m cyst was encapsulated, measured 22×20 ×20 cm and weighed 3800 g. The unilocular cavlty was filled with much. Most of the cystic cavity was lined with tall, slmple or stratifled columnar eplthellum wlth a focus of papillary provon into the cavity. These findings suggest that this cystic lesion represents cystadenoma rather than a simple cyst. Foci of lnvasive moderately differentiated mucinous adenocarclnoma were detected in the area of macroscopic papillary fronds. Carcinoembryonic antigen and CA19–9 were immunohistochemically positive for tumor cells and their serum levels were also elevated. Stromal dystrophic calcification was extensively observed In the cyst wall with focl of osseous metaplasia. Muclnous Implants, whlch histologically demonstrated adherent muclnous masses without epithellal components on the surface, were observed in the pelvic and abdominal cavity, lndicating pseudomyxoma peritonei.     

Primary leiomyoma of the ovary co-existing with serous cystadenofibroma

A 48-year-old woman with a 14 cm left ovarian mass had total abdominal hysterectomy and bilateral salpingo-oophorectomy. On cut section the tumor had a solid and a cystic component. There was a 2.5 cm nodule attached to the cyst wall. Sections taken from the solid component revealed a tumor composed of interlacing bundles of fusiform cells, resembling a leiomyoma. Smooth muscle actin positivity confirmed the diagnosis. Sections taken from the nodule in the cystic part revealed an adenofibroma. There was an SMA positive area in the cyst wall which we think is the possible origin of the leiomyoma. As far as we know, this is the first case of a co-existing leiomyoma and serous cystadenofibroma in the ovary, and we think it will broaden the histological spectrum of primary ovarian leiomyomas.     

Squamous cell carcinoma arising in a ciliated hepatic foregut cyst

We report a case of squamous-cell carcinoma arising in a ciliated hepatic foregut cyst that occurred in a 21-year-old man. The cystic lesion was first discovered during childhood with no further follow-up. Following important weight loss over several months, the patient was admitted to our hospital where a CT scan showed a cystic and solid mass in segments V and VI of the liver involving the transverse mesocolon and the gastric antrum. A right hepatectomy with en-bloc right hemicolectomy and partial gastrectomy was performed. Gross examination showed a partially cystic liver mass with a maximum dimension of 10 cm infiltrating the large bowel wall. Microscopically, it was a poorly differentiated squamous-cell carcinoma arising from the wall of a liver cyst lined by a ciliated, pseudostratified columnar epithelium. Hepatic foregut cysts are uncommon, congenital, benign lesions that, when discovered, deserve careful clinical follow-up as malignant transformation, albeit exceptional, is possible.     

Ductal adenocarcinoma of the pancreas with huge cystic degeneration: a lesion to be distinguished from pseudocyst and mucinous cystadenocarcinoma

Cystic neoplasms of the pancreas are rare and often mistaken for pseudocyst by imaging studies and macroscopic examination. We describe an unusual tumor of the pancreas composed of a mural nodule of anaplastic carcinoma arising from a huge ductal adenocarcinoma undergoing cystic degeneration. The cyst measured 27 x 13 x 4 cm. Light microscopy showed that the cyst was partly lined by a single layer of cuboidal to columnar tumor cells with focal mucin production and was surrounded by hyalinized connective tissue. Most lining epithelial cells were absent owing to extensive degenerative process. Immunohistochemical studies showed positive staining of cytokeratin and vimentin for pleomorphic giant tumor cells, which were negative for leukocyte common antigen (CD45), KP-1 (CD68), epithelial membrane antigen (EMA), and carcinoembryonic antigen (CEA). The ductal adenocarcinoma stained strongly positive for cytokeratin and EMA, and negative for vimentin, CD45, CD68, and CEA. The clinical course of the current case was extremely poor and the prognosis resembled that of an anaplastic carcinoma. Therefore, we like to emphasize the importance of complete excision and extensive sampling of any cystic neoplasms in the pancreas including those with large cystic component to avoid missing the malignant elements.