[Metastatic tumors in the ovary, difficulties of histologic diagnosis]. / A petefészek áttéti tumorai, a szövettani diagnosztika problémái.

The ovary is a common site of metastases. Secondary tumors account for 3-40% of all ovarian malignancies. Most ovarian metastases arise from the colon, although tumors of the breast, stomach and endometrium are also common places of origin. Clinical and histological features of metastatic tumors frequently mimic primary ovarian malignancies, causing serious diagnostic problems for the surgical pathologist. However, differentiation between primary ovarian cancer and ovarian metastasis is important in order to prevent inappropriate management and suboptimal treatment. The distinction between primary and secondary ovarian malignancies is especially difficult in cases when the metastasis is diagnosed before the primary tumor. Frozen section is widely used in the intra-operative assessment of patients with ovarian tumors but it can be very difficult to distinguish certain types of primary ovarian tumors and metastases from other sites. We examined 152 cases of secondary ovarian neoplasm diagnosed at the National Institute of Oncology, Hungary from 2000 to 2014. Colorectal cancer was the most common primary tumor (58 cases), followed by breast (33 cases), endometrium (30 cases) and stomach cancer (13 cases). The differential diagnosis proved the most difficult in cases when endometrioid and mucinous tumors were present in the ovaries. Metastases of colorectal and gastric adenocarcinomas may simulate benign or borderline cystadenomas too. In these cases the knowledge of the patient's history and immunohistochemical stains were helpful. In our study we discuss the diagnostic challenge of distinguishing these secondary ovarian tumors from primary ovarian neoplasms and the limits of the intraoperative frozen sections.

Paraaortic paraganglioma arising in an ovarian carcinoma patient mimicking lymph node metastasis.

Paragangliomas are rare tumors arising from the chromaffin cells in the autonomic nervous system. While they both occur most frequently along the paraaortic chain, paraganglioma and ovarian carcinoma very rarely occur together. A 61-year-old, post-menopausal woman visited our hospital, with complaints of abdominal pain and genital bleeding. Image analysis showed a 21 x 18 x 10 cm ovarian mass, and a 38 mm tumor at the paraaortic lesion. First, she underwent bilateral salpingo-oophorectomy. Serous papillary cystadenocarcinoma of the left ovary was found, and so a second surgery was performed. The paraaortic tumor was completely eliminated in spite of fluctuating blood pressure intraoperatively. Microscopic examination revealed that the paraaortic tumor was paraganglioma. She was ultimately diagnosed as having ovarian carcinoma stage Ia (FIGO) with coincident paraganglioma. If blood pressure fluctuation is observed during dissection of the paraaortic lymph node, paraganglioma should be suspected and blood pressure must be carefully controlled.

Guanylyl cyclase C is a specific marker for differentiating primary and metastatic ovarian mucinous neoplasms.

AIMS: The aim was to assess the value of GCC in distinguishing primary ovarian mucinous neoplasms from metastatic mucinous adenocarcinomas with ovarian involvement. Guanylyl cyclase C (GCC) is a brush border membrane receptor for the endogenous peptides guanylin and uroguanylin, and the homologous diarrhoeagenic bacterial heat-stable enterotoxins that is selectively expressed by epithelial cells from the duodenum to the rectum, but not by normal epithelia of the stomach or oesophagus, or normal extramucosal cells in humans. METHODS AND RESULTS: Fifty ovarian tumours: 27 primary ovarian mucinous neoplasms (seven cystadenomas, 10 borderline tumours and 10 cystadenocarcinomas) and 23 metastatic mucinous adenocarcinomas with ovarian involvement [13 colorectal adenocarcinomas, four gastric adenocarcinomas, six appendiceal mucinous tumours (four adenocarcinomas, one with neuroendocrine features, and two appendiceal mucinous cystadenomas)] were studied. For primary ovarian mucinous neoplasms, 25 of 27 were negative for GCC. Twelve of 13 cases of colorectal adenocarcinoma (except for one neuroendocrine adenocarcinoma) were positive for GCC. Three of four appendiceal mucinous adenocarcinomas were positive for GCC in both the primary and metastatic tumours (except for one neuroendocrine adenocarcinoma). Two of two appendiceal mucinous cystadenomas were positive for GCC. Of four cases of gastric adenocarcinoma with ovarian involvement, only one (primary tumour) exhibited focal GCC staining. CONCLUSIONS: GCC is a useful marker for differentiating between primary and secondary ovarian mucinous neoplasms.

Cell growth stimulation by CRASH, an asparaginase-like protein overexpressed in human tumors and metastatic breast cancers.

The gene encoding CRASH, a human asparaginase-like protein, has been cloned and its transcriptional activation has been detected in gynecologic cancers. To define the expression of CRASH in human tumors and its possible functional role, monoclonal antibodies against the CRASH protein have been generated. In non-transformed tissues CRASH was only detected in testis, brain, esophagus, prostate and proliferating endometrium. On the other hand, 36/50 ovarian carcinomas, 16/78 mammary carcinomas, 6/6 uroepithelial bladder carcinomas and 5/33 colon carcinomas scored positive for CRASH, with the absence of reactivity in the corresponding normal tissues. Strikingly, 11 out of the 16 breast cancers that expressed CRASH were metastatic, nominating CRASH to be functionally relevant in tumor progression. Twenty-eight out of 42 endometrium tumors expressed CRASH at high levels as did 5/41 prostate carcinomas, as well as ovary and breast cancers, indicating a regulation of CRASH expression by sex hormones. A bona fide estrogen responsive element was detected at bases -201/-183. This proved to be highly preserved across species, supporting an actual functional role. Asparaginase-like proteins play a role in growth regulation and signaling by p70 S6 kinase. The somatic knock-out of CRASH resulted in significant inhibition of growth of KM12L4A colon carcinoma cells, which abundantly express CRASH, whereas the proliferation of the syngeneic, weakly-expressing, slowly-growing KL12SM was not affected. These results are consistent with a selective growth advantage for aggressive cancers expressing CRASH, and nominate CRASH as a novel diagnostic and therapeutic tumor target.

Malignant solitary fibrous tumor of the kidney with liver metastasis: A case report and literature review.

Solitary fibrous tumor (SFT) is a rare spindle cell soft tissue tumor which is rarely encountered in the clinical setting and imaging findings are nonspecific, mainly occurring in the tissue structure of the serosa. However, there is very little report on SFT originating in the kidney in the medical literature. We report a case of SFT with liver metastasis in an adult female and discuss the pathological features as it appears in our case.

PIK3CA and PTEN mutations in adenoid cystic carcinoma of the breast metastatic to kidney.

Adenoid cystic carcinoma (ACC) of the breast rarely metastasizes and has been associated with excellent prognosis. We describe a patient with renal metastasis of primary breast ACC 5 years after the mastectomy. A detailed molecular genetic analysis of the primary and metastatic tumors demonstrated somatic mutations in 2 well-known cancer genes associated with regulation of PI3K/AKT signaling pathway: (1) PIK3CA, which encodes the catalytic alpha subunit of the phosphoinositide-3-kinase, and (2) PTEN, which encodes phosphatase and tensin homolog. The mutation identified in PIK3CA (Ex1+169 A>C) predicts an amino acid change from isoleucine to methionine at codon 31 (I31M) and resides in the p85-binding domain of exon 1. The mutation identified in PTEN (IVS4-3 C>T) resides in intron 4 near the splice acceptor site of exon 5 and was associated with an aberrant PTEN transcript lacking exon 5, which is necessary for protein tyrosine phosphatase function and tumor suppressor properties of PTEN. Increased promoter methylation of PTEN was present in renal metastasis, coinciding with the decrease in the level of normal PTEN transcript. These coexistent mutations/epigenetic inactivations in PI3K/AKT pathway may be responsible for the unusually aggressive course of ACC.

Metastatic lymph node impostor in pancreatic cystadenocarcinoma.

CONTEXT: Lymph node involvement in pancreatic cancer is a predictor of poor patient long-term survival. The detection of multiple metastatic peri-pancreatic nodes by EUS-FNA may dissuade the surgeon from undertaking a curative pancreatic resection. CASE REPORT: We report an interesting case of a man with chronic lymphocytic leukemia, who presented with the diagnostic problem of a pancreatic solid-cystic lesion and multiple malignant-looking peri-pancreatic lymphadenopathy on EUS. EUS-FNA yielded chronic lymphocytic leukaemia involvement in the peri-pancreatic lymph nodes and a markedly elevated CEA in the cystic fluid. The absence of adenocarcinoma involvement of the lymph nodes prompted surgery on the pancreatic lesion with a curative intent. Pancreatic mucinous cystadenocarcinoma was diagnosed and a sub-total pancreatectomy was performed with clear resection margins. All 30 resected peri-pancreatic lymph nodes showed chronic lymphocytic leukemia involvement only. CONCLUSIONS: This case illustrates that abnormal lymphadenopathy adjacent to a primary pancreatic lesion may not necessarily be due to the latter. Systemic lymphoproliferative disease, as in this case, can masquerade as metastatic adenocarcinoma lymph nodes on EUS. EUS-FNA is useful in diagnosing lymphoproliferative disease.

Bilateral metastatic breast cancer as the first manifestation of ovarian cancer: case report.

BACKGROUND: Breast metastasis from primary ovarian cancer is extremely rare. The rarity of this finding may be the reason for its common misinterpretation as primary breast carcinoma. DESIGN: Case report. SETTING: A university hospital. RESULTS: A case of a patient with primary ovarian papillary serous cystadenocarcinoma who initially presented with a solitary bilateral breast mass and abdominal distention is reported. CONCLUSIONS: Blood-borne metastasis from the ovary to the breast can show a varied clinical picture that should be differentiated from that of primary breast carcinoma.

[Cerebellar metastasis from ovarian carcinoma. A case report]. / Przerzut do mózdzku w przebiegu raka jajnika.

This report presents an unusual case of 40-year-old woman with complete locoregional remission of ovarian carcinoma, presented with a single cerebellar metastasis. Surgical excision of the cerebellar lesion, followed by brain irradiation, resulted in complete resolution of her symptoms.

Postoperative whole abdomino-pelvic irradiation for patients with high risk endometrial cancer.

Forty-seven patients with endometrial cancer, surgical Stage I through IV, received adjuvant whole abdomino-pelvic irradiation with a nodal and vaginal boost between August 1981 through December 1986. The median age was 66.5 years (range 37-86 years). Twenty-two patients were Stages I-II, 14 Stage III, and eleven patients Stage IV. Thirty-four patients (79%) had positive peritoneal cytology, 29 patients (62%) had deep myometrial involvement, 27 patients (58%) had high grade lesions, 18 patients (40%) had either serous-papillary or adenosquamous histologic variants, and ten patients (22%) had residual disease of up to 2 cm. remaining after operation, mostly in the form of nodal disease. Twenty-four patients (51%) had two or more life time laparotomies. Mean follow-up was 40.5 mo. (range 17-85 mo.). The 5-year actuarial survival was 68% and the 5-year relapse-free survival (RFS) was 77%. The 5 year relapse-free survival for Stages I/II, III, and IV were 85%, 78%, and 53%, respectively. The 5 year relapse-free survival for grades 1/2 was 100% and for grades 3/4 was 60%. (p value of 0.0017). Acute toxicity has been modest, and particularly evident in thinner patients (weight below 115 lbs.). Chronic toxicity of significance has been limited to one patient with a conservatively managed bowel obstruction. These results are very encouraging and suggest benefit to the use of more aggressive adjuvant irradiation.

Abdominopelvic irradiation for persistent advanced ovarian carcinoma.

The efficacy and toxicity of abdominopelvic irradiation following chemotherapy and positive second look laparotomy was assessed in 15 patients with advanced ovarian epithelial carcinoma. The patients received 30 Gy abdominal and 50.4 Gy pelvic irradiation. Three of ten patients with minimal disease are disease-free 30+, 72+, and 78+ months following therapy. A fourth patient survives disease-free 24+ months following third laparotomy. No patient with bulky disease is disease-free. Bowel obstruction was encountered in 5 of 15 patients; all episodes were associated with recurrent tumor. Abdominopelvic irradiation can potentially sterilize minimal volume ovarian carcinoma that persists following chemotherapy.

Serous adenocarcinoma of the uterus metastatic to the urinary bladder mimicking primary bladder neoplasia. A report of a case.

A 72-year-old woman with a history of transitional cell carcinoma of the urinary bladder was found to have a vesical neoplasm at cystoscopy. Microscopic examination of a biopsy specimen showed papillary adenocarcinoma. A subsequent endometrial biopsy, performed because of vaginal spotting, disclosed a serous papillary adenocarcinoma. A hysterectomy was performed. Pathologic examination showed that the tumor was deeply invasive of the myometrium. The uterine and bladder tumors were similar histologically. This case suggests that when examining a pure adenocarcinoma of the bladder, the pathologist should consider the possibility that it represents metastatic disease even in the absence of a known tumor elsewhere.

Serous cystadenocarcinoma of the pancreas: a new entity?

Microcystic cystadenoma of the pancreas is a well-recognized although rare pathological entity. All previously reported examples of this tumor have been uniformly benign in behavior. In this case report, we present a primary tumor of the pancreas that was histologically indistinguishable from microcystic adenoma, but which behaved in a malignant fashion. Metastases were found in the stomach and liver. We believe that this case represents a new entity, which we have termed "serous cystadenocarcinoma of the pancreas."

False-positive lymph nodes by radioimmunoguided surgery: report of a patient and analysis of the problem.

Preoperative administration of radiolabeled monoclonal antibody allows radioimmunoguided surgery with hand-held intraoperative detection devices. From a theoretical perspective, this technology may offer more knowledgable patient management and more complete resection of intra-abdominal cancer. False-positive examinations may seriously jeopardize the widespread application of this apparatus. Our experience with a patient with false-positive lymph nodes following administration of 125I-labeled B72.3 monoclonal antibody is reported. After careful histopathological analysis of five nodes thought to be false-positive for cystadenocarcinoma, one lymph node was found to have a minute nidus of cancer. The cause of false-positive radioimmunoguided tests and their implications for the clinical use of this tool is discussed. We interpreted our data to suggest that tumor antigen-monoclonal antibody complexes processed in reactive lymph nodes, anatomically draining the malignant tissue, may cause false-positive tests.

Interactive morphometry of normal and hyperplastic peritoneal mesothelial cells and dysplastic and malignant ovarian cells.

This study used computerized interactive morphometry to evaluate the differential characteristics of mesothelial normal cells, mesothelial hyperplastic cells, and carcinomatous cells, and also compared hyperplastic mesothelial cells with ovarian dysplastic cells from a previous study. The procedure included extraction of multiple descriptors of the nuclear profile: perimeter length, area, longest chord, circularity factors, standard deviations of these characteristics, and a 10-bin size distribution table of the nuclear area. The final classification is achieved by stepwise discriminant analysis of these variables. The analysis classified all cases correctly with high posterior probabilities.

Ovarian carcinoma metastatic to the breast and axillary node.

Breast cancer is a common primary malignancy in women. On rare occasion the breast is also the site of metastatic disease. This report describes the evaluation of breast and axillary masses in a patient with known ovarian cancer, including the radiographic evaluation and special immunohistochemical stains with CA-125. Flow cytometric determinations and hormonal receptor analysis on both the primary and metastatic tumors demonstrate similar biologic characteristics. Both tumor sites demonstrated positive CA-125 staining, aneuploid DNA populations, moderately positive estrogen receptor content, and negative progesterone receptors. The mammogram demonstrated a well-circumscribed lesion with several areas of microcalcifications. Blood-borne metastasis from the ovary to the breast can show a varied clinical picture that can be differentiated from that of a primary breast carcinoma.

Ovarian cancer associated with the nephrotic syndrome.

A 65-year-old woman was found to have the nephrotic syndrome eight months before the onset of a new left neck mass. Biopsy specimen of the mass showed metastatic adenocarcinoma, which was subsequently found to be from an ovarian primary. Operation and triple chemotherapy has markedly diminished the degree of proteinuria. Although uncommon, ovarian carcinoma must be considered in the differential diagnosis of cancer-related nephrotic syndrome.

Modified posterior exenteration for ovarian cancer.

The operative description of a modified posterior exenteration along with operative findings, other operative procedures, postoperative course, and follow-up information are presented for 47 patients (37 primary cytoreduction, ten secondary cytoreduction). All had stage IIIC or IV epithelial ovarian cancer with pelvic disease encasing the reproductive organs, pelvic peritoneum, cul-de-sac, and sigmoid colon. In addition to modified posterior exenteration, all patients had multiple other procedures performed as part of the cytoreductive efforts. Forty-five (95.7%) had optimal (less than 2 cm) cytoreduction and 18 (38.3%) had complete cytoreductive surgery. Thirty-four patients were ultimately rendered continent of feces (25 primarily and nine after colostomy reversal). Nine patients (19.1%) had serious morbidity and one (2.1%) died postoperatively. The median follow-up for those undergoing primary cytoreduction was 13.3 months (6-84). Nineteen (51.4%) were alive at the time of writing, 16 (43.2%) were dead, and two (5.4%) were lost to follow-up. Modified posterior exenteration effectively removes all visible pelvic disease with acceptable mortality. Hence, even patients with the most advanced cases of ovarian cancer may attain optimal cytoreduction and become ideal candidates for adjunctive therapy, with improved survival or a chance for cure.

Surgical reversal of a subacute complete unilateral visual loss from an ovarian metastasis to the pituitary gland.

A 56-year-old woman with ovarian papillary cystadenocarcinoma that metastasized to the pituitary gland sought treatment with a 7-day history of total loss of vision in one eye. Ten days after transsphenoidal tumor resection, the patient's vision suddenly returned to baseline. This unusual case indicates that surgical decompression of the optic nerve and chiasm can completely salvage vision, even after prolonged total visual loss.