Syringocystadenocarcinoma Papilliferum In Situ, a Variant of Cutaneous Adenocarcinoma In Situ: A Case Report With Literature Review.

Syringocystadenocarcinoma papilliferum in situ, a variant of cutaneous adenocarcinoma in situ, is extremely rare. Only 9 cases have been published to date with 2 cases demonstrating pagetoid epidermal involvement. In this study, we report a case of syringocystadenocarcinoma papilliferum in situ with pagetoid epidermal involvement arising from a long-standing nevus sebaceus on the scalp of a 60-year-old woman.

Syringocystadenocarcinoma Papilliferum In Situ-Like Changes in Extramammary Paget Disease: A Report of 11 Cases.

The authors report 11 cases of extramammary Paget disease (EMPD), all of which also demonstrated a combination of histological changes highly reminiscent of syringocystadenocarcinoma papilliferum in situ. In addition to the classical features of EMPD, characterized by the intraepidermal spread of individually dispersed neoplastic cells with ample cytoplasm, many of which contained mucin, there were areas of acanthosis with the substitution of spinous layer keratinocytes by neoplastic cells, whereas the native basal cell layer was intact. In addition to acanthosis (and sometimes papillomatosis), the dermal papillae showed a prominent infiltrate of plasma cells, completing the resemblance to syringocystadenocarcinoma papilliferum in situ; this similarity was further enhanced in 2 cases, which showed conspicuous gland formation. One additional case showed multifocal dermal proliferations compatible with eccrine syringofibroadenoma (syringofibroadenomatous hyperplasia). The changes described herein seem to be relatively rare in EMPD, and they can represent a diagnostic pitfall, as evidenced by 2 cases that were originally misinterpreted as syringocystadenocarcinoma papilliferum in situ. Clinically, these microscopic changes sometimes corresponded to nodular lesions, which were specifically noted to have a papillated erosive surface.

Metastatic ovarian papillary cystadenocarcinoma to the small intestine serous surface: report of a case of high-grade histopathologic malignancy.

Ovarian cystadenocarcinoma is characterized by marked heterogeneity and may be composed of an admixture of histologic growth patterns, including acinar, papillary and solid. In the present study, a case of isolated small intestine metastasis of ovarian papillary cystadenocarcinoma was reported. A 7-year-old female mixed-breed dog presented with a mass in the left upper quadrant with progressive enlargement of the abdomen, periodic bloody discharge from the vulva and incontinence. The tumor was histologically characterized by the presence of cysts and proliferation of papillae, both lined by single- or multi-layered pleomorphic epithelial cells. Furthermore, the mass was composed by intense cellular and nuclear pleomorphism and numerous mitotic figures. These findings indicate a tumor of high-grade malignancy with infiterative tumor cells resembling the papillary ovarian tumor in the serosal surface of the small intestine along with an intact serosa. Immunohistochemically, tumor was positive for CK7 and negative immunoreactivity for CK20. The histopathologic features coupled with the CK7 immunoreactivity led to a diagnosis of high grade ovarian papillary cystadenocarcinoma. To the best of our knowledge, this is the first case of small intestine serousal surface metastasis from ovarian papillary cystadenocarcinoma.

Syringocystadenocarcinoma papilliferum with transition to areas of squamous differentiation: a case report and review of the literature.

Syringocystadenocarcinoma papilliferum (SCACP) is an exceedingly rare cutaneous adnexal neoplasm, which is typically located in the head and neck, and perianal area. Very few cases have been reported in the literature. Here, we report a case of SCACP with evident transition to squamous differentiation. A 75-year-old white woman presented with 1-year history of a solitary tender nodule in the left upper arm. Physical examination revealed a single, 1.5 × 1.1-cm, erythematous ulcerated nodule within a background of red patch. Biopsy showed an adnexal carcinoma connected to the epidermis and composed of cystic papillary projections admixed with solid basaloid areas with marked cytologic atypia. The basaloid tumor cells appeared to blend with the squamous component that demonstrated ductal formation, which was highlighted by carcinoembryonic antigen. Tumor cells were reactive for both cytokeratins 5/6 and 7. This case represents SCACP arising from syringocystadenoma papilliferum in the upper arm, with distinct transition to areas of squamous differentiation.

A case of serous endometrial intraepithelial carcinoma with p53 positivity for six years.

A 69-year-old postmenopausal woman was referred because she had been taking tamoxifen for four years. Tissues obtained by endometrial curettage were immunopositive for p53, but there was no definite malignancy. At age 73, cytology again showed abnormalities, so we repeated complete endometrial curettage. Again, there was no malignancy, but p53 immunostaining was widely positive. At age 75, hysterectomy was performed because cytological examination showed increasingly abnormal findings and the patient opted for surgery. In the resected uterus, endometrial glands were replaced by malignant cells resembling papillary serous carcinoma cells with high-grade nuclei, but there was no stromal or myometrial invasion. The pathological diagnosis was intraepithelial serous endometrial carcinoma. This is a rare case because we could follow the patient for 6 years by endometrial cytology or endometrial curettage and we observed gradual transformation into endometrial intraepithelial carcinoma.

A case of intratesticular endometrioid papillary cystadenocarcinoma.

We report a case of intratesticular endometrioid papillary cystadenocarcinoma. A 73-year-old man was admitted for a painless right scrotal swelling. Ultrasonography and computed tomography revealed a large cystic mass in the right testis. Right scrotum puncture revealed xanthochromic fluid with negative cytology. Three months later, follow-up computed tomography showed enlargement of the cystic mass. Right high orchiectomy was performed because a testicular malignancy was suspected. The pathological diagnosis was endometrioid papillary cystadenocarcinoma, and the cells were strongly positive for the estrogen and progesterone receptors. Testicular neoplasms resembling common ovarian-type epithelial tumors are very rare. This is the first report of endometrioid papillary cystadenocarcinoma of the testis.

Expression of PLUNC family members in benign and malignant salivary gland tumours.

OBJECTIVES: The aim of this study was to determine the expression of PLUNC proteins in benign and malignant salivary gland tumours and thus their potential use as diagnostic and / or prognostic tools. MATERIALS AND METHODS: A tissue microarray was assembled from 64 salivary gland tumours including adenoid cystic carcinoma, carcinoma ex-pleomorphic adenoma, mucoepidermoid carcinoma, polymorphous low-grade adenocarcinoma, pleomorphic adenoma, acinic cell carcinoma, myoepithelial carcinoma and papillary cystadenocarcinoma. Clinicopathological data were collected retrospectively and immunohistochemical analysis of three PLUNC proteins (SPLUNC1, SPLUNC2 and LPLUNC1) was performed. Immunoreactivity was assessed as positive or negative. RESULTS: PLUNC expression was only found in mucoepidermoid carcinomas and papillary cystadenocarcinoma; all other tumours studied were negative. Mucin plugs, mucous and intermediate cells of mucoepidermoid carcinomas were positive for LPLUNC1 and SPLUNC2, but areas composed of epidermoid and clear cells were negative for all PLUNCs. Papillary cystadenocarcinoma was positive for all PLUNCs. No correlation was found with tumour grade or outcome. CONCLUSIONS: Intense expression of two PLUNC proteins in mucous cells and mucin plugs of mucoepidermoid carcinoma and papillary cystadenocarcinoma indicate that they could be used as additional diagnostic tools in some equivocal cases, but further studies are needed to understand the biological processes involved in PLUNC expression.

Cystic neoplasms of the exocrine pancreas.

The increasing use of radiological imaging has led to greater detection of small and asymptomatic cystic lesions of the pancreas. Most are resectable, but not all are neoplastic. This review provides an update on the histopathology, immunohistochemistry, molecular biology, pathogenesis and management of cystic neoplasms of the exocrine pancreas. These include the serous, the mucinous cystic, the intraductal papillary mucinous and the solid pseudopapillary neoplasms. Recently reported variants are described and very rare cystic variants of other pancreatic epithelial and mesenchymal neoplasms are briefly mentioned.

Expression of PAX2 in papillary serous carcinoma of the ovary: immunohistochemical evidence of fallopian tube or secondary Müllerian system origin?

PAX2 is a urogenital developmental transcription factor expressed in the Wolffian ducts, developing kidneys, and Müllerian ducts during embryonic stage. Its function in renal development is well documented and its clinical application in the diagnosis of lesions of renal origin has been reported recently. However, information on its role in the Müllerian-derived genital tract is sparse. In this study, we investigated the expression of PAX2 in human female genital tract using immunohistochemistry. We demonstrated that PAX2 was expressed specifically in the epithelial cells of fallopian tube, endometrial and endocervical glands, but not in the stromal tissues in these areas. PAX2 was detected in secondary Müllerian structures in the ovary, such as endometriotic and endosalpingiotic glands and rete ovarii, but not in ovarian surface epithelium, surface epithelium-derived inclusion cysts, stroma, or sex-cord-derived structures such as follicles, oocytes, and corpus luteum. In addition, PAX2 was detected in 67% of ovarian papillary serous carcinomas (N=36) but rarely in peritoneal malignant mesotheliomas, with two exceptions (N=54). Interestingly, the two PAX2-positive 'peritoneal malignant mesotheliomas' were from female patients and were positive for estrogen receptor. The significance of expression of PAX2 and estrogen receptor in these cases is under investigation. Taken together, we suggest that PAX2 is a novel Müllerian-specific epithelial marker when used in proper clinical settings. Identification of PAX2 in the majority of papillary serous carcinomas of the ovary but not in the ovarian surface epithelium or epithelium-derived inclusion cysts suggests that this malignant epithelial tumor may be directly derived from the primary or secondary Müllerian epithelium in or surrounding the ovary, rather than from the surface epithelium or its derivatives.

Abnormalities of the RB1 pathway in ovarian serous papillary carcinoma as determined by overexpression of the p16(INK4A) protein.

Dysfunction of proteins involved in the G1 to S transition of the cell cycle, such as p16(INK4A) and RB1, is common in many cancer types. A screen of p16 protein expression was performed in benign, borderline, and invasive ovarian tumors, together with endometrial cancers, aligned on a tissue microarray. We observed frequent p16 overexpression in serous papillary carcinomas of ovarian and endometrial origin. An extended cohort of ovarian serous papillary carcinomas was examined to further evaluate the frequency of p16 overexpression. Strong, uniform staining in the majority of cancer cells occurred commonly in invasive serous papillary ovarian cancers, particularly in grade 3 carcinomas. RB1 protein expression abnormalities were rare. Our data indicate that abnormalities in the retinoblastoma pathway, as determined by p16 overexpression, are common in serous papillary carcinomas and are probably an early event.

The value of serum and tissular expression of CA 125 antigen, in evaluation of the response to second line chemotherapy for the relapsed ovarian carcinoma.

PURPOSE: The purpose of this study is to compare the predicted value of the blood levels variations of CA 125 antigen and the imunohistochemical expression of CA 125, with imagistic criteria (The Response Evaluation Criteran in Solid Tumor--RECIST) regarding the survival estimation of female patients with relapsed ovarian carcinoma which undergo to second line chemotherapy. MATERIAL AND METHOD: We included in this study 40 female patients diagnosed with ovarian carcinoma in the Oncology Clinic of the Emergency County Hospital Craiova, in a period of two years (from 2000 to 2002), which have fulfilled the following criteria: ovarian carcinoma IC-IV stage, according to FIGO system, first line treatment represented by the association between paclitaxel and a platinum salt, refractory or recurrent disease, indications for beginning the second line chemotherapy represented by topotecan or paclitaxel and carboplatin. The serial CA 125 antigen was determined in all patients before starting the chemotherapy and after each two sequences of chemotherapy, and the imunohistochemical expression of CA 125 was evaluated from surgery extracts before the second line chemotherapy (11 cases). The imagistic evaluation of the treatment response was done after 4 sequences of chemotherapy. RESULTS: All patients had measurable disease according to RECIST criteria and had high values (at least double) of the CA 125 antigen blood level at the time of diagnosis. The imunohistochemically expression of CA 125 was correlated in most cases with the blood level of CA 125. The evaluation criterion of the CA 125 antigen has been shown to be more efficient in estimation the survival rate compared with the RECIST system. In a various analysis, which included numerous potential prognostic factors, only the variation of blood levels of these antigen and the free disease interval from the finalization of the first line chemotherapy have been identified as predictive factors of survival, while the other variables, including the RECIST criteria, had no impact on the prognosis regarding the survival. CONCLUSIONS: The response evaluation criteria based on the blood levels variations of CA 125 antigen are a better instrument for the estimation of the compared prognosis with the RECIST criteria, for patients on second line chemotherapy for relapsed ovarian carcinoma.

Papillary serous carcinoma of the ovary: an ultrastructural and immunohistochemical study.

Twenty-four patients with ovarian serous papillary carcinoma were enrolled in the present ultrastructural and immunohistochemical study. Immunohistochemistry was used to examine the status of proliferation activity with antibodies against Ki67 and BM28, and the status of EGFR family members with antibodies against EGFR, c-erbB-2, and c-erbB-4. Ultrastructurally, poorly differentiated tumors often revealed solid sheets of tumor cells with variable desmosomes, cell connection complexies, and microvilli. No mature cilia, which are often present in benign and borderline ovarian epithelial tumors, were seen in these 24 carcinomas. However, two poorly differentiated tumors demonstrated oligocilia. In addition, numerous secondary lysosomes and bizzare intracytoplasmic pseudocavities were more often present in the poorly differentiated tumors. Immunohistochemically, strong expressions of BM28 and Ki67 in more than 50% of the tumor cells were found in 12/15 (80%) and 11/15 (73%) of the poorly differentiated tumors, respectively, compared with 3/9 (33%) and 1/9 (11%) of the moderately differentiated tumors, respectively. Higher levels of EGFR and c-erbB-2 expressions were more often observed in the poorly differentiated tumors, compared with that in the moderately differentiated tumors. In conclusion, oligocilium, numerous secondary lysosomes, and bizarre intracytoplasmic inclusions are more often seen in poorly differentiated ovarian serous carcinomas. Poorly differentiated ovarian serous carcinomas express higher levels of Ki67, BM28, EGFR, and c-erbB-2 proteins.

Characterization of human mesothelin transcripts in ovarian and pancreatic cancer.

BACKGROUND: Mesothelin is an attractive target for cancer immunotherapy due to its restricted expression in normal tissues and high level expression in several tumor types including ovarian and pancreatic adenocarcinomas. Three mesothelin transcript variants have been reported, but their relative expression in normal tissues and tumors has been poorly characterized. The goal of the present study was to clarify which mesothelin transcript variants are commonly expressed in human tumors. METHODS: Human genomic and EST nucleotide sequences in the public databases were used to evaluate sequences reported for the three mesothelin transcript variants in silico. Subsequently, RNA samples from normal ovary, ovarian and pancreatic carcinoma cell lines, and primary ovarian tumors were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and nucleotide sequencing to directly identify expressed transcripts. RESULTS: In silico comparisons of genomic DNA sequences with available EST sequences supported expression of mesothelin transcript variants 1 and 3, but there were no sequence matches for transcript variant 2. Newly-derived nucleotide sequences of RT-PCR products from tissues and cell lines corresponded to mesothelin transcript variant 1. Mesothelin transcript variant 2 was not detected. Transcript variant 3 was observed as a small percentage of total mesothelin amplification products from all studied cell lines and tissues. Fractionation of nuclear and cytoplasmic RNA indicated that variant 3 was present primarily in the nuclear fraction. Thus, mesothelin transcript variant 3 may represent incompletely processed hnRNA. CONCLUSION: Mesothelin transcript variant 1 represents the predominant mature mRNA species expressed by both normal and tumor cells. This conclusion should be important for future development of cancer immunotherapies, diagnostic tests, and gene microarray studies targeting mesothelin.

Endoglin (CD105) expression in endometrial carcinoma.

Tumor angiogenesis plays an important role in tumor growth and metastasis. We evaluated endoglin (CD105) as an endothelial marker of angiogenesis in endometrial carcinoma (EC) and its prognostic significance. Fifty-five cases of EC, 10 cases of complex endometrial hyperplasia with atypia (CHA), and 10 cases of simple hyperplasia (SH) were immunohistochemically stained for endoglin, CD31, and vascular endothelial growth factor (VEGF). Positively stained microvessels (MV) were counted in densely vascular foci (hot spots) in a 400x field in each specimen. For VEGF, intensity of staining was scored on three-tiered scale. Results were correlated with other prognostic parameters using appropriate statistics. Endoglin staining demonstrated significantly more MV than did CD31 (mean 30.8 +/- 10.95 vs. 13.38 +/- 7.53, p < 0.001). There was a positive correlation of both endoglin and CD31 MV counts with tumor differentiation (p < 0.05) and the depth of invasion (p < 0.01). However, only endoglin counts correlated significantly with the presence of angiolymphatic invasion (p < 0.01), lymph nodes metastases (p < 0.01), and tumor stage (p < 0.001). VEGF expression in EC had a significant correlation with angiolymphatic invasion (p < 0.01) and lymph node status (p < 0.05) but not with other prognostic parameters. Endoglin and VEGF showed significant differences between CHA and SH (p < 0.001). Our study showed that endoglin, by staining the proliferating MV in EC, is a more specific and sensitive marker for tumor angiogenesis than is the commonly used pan-endothelial marker, CD31. Endoglin staining also had prognostic significance, with positive correlation with angiolymphatic invasion, lymph node metastases, and tumor stage.

Expression of growth hormone-releasing hormone in human primary endometrial carcinomas.

BACKGROUND: Hypothalamic GH-releasing hormone (GHRH) regulates GH release from the pituitary, but an ectopic production of GHRH has been detected in various non-hypothalamic tissues, especially cancers. OBJECTIVE: To investigate whether endometrial tumors produce GHRH. METHODS: Twenty-four endometrioid, three serous papillary (SP), three mixed type endometrioid/serous papillary adenocarcinomas and one malignant mixed Müllerian tumor (MMMT) were assessed for GHRH immunoreactivity by the polyclonal anti-rabbit antibody SV95 and for the expression of GHRH mRNA by in situ hybridization using an oligonucleotide probe. RESULTS: Increased GHRH immunoreactivity was detected in 15 out of 24 (63%) of the endometrioid tumors, including two out of three (66%) of the mixed type endometrioid/serous adenocarcinomas but not in the three SP or the MMMT tumor. Cytoplasmic staining was detected in all positive cases, while in three of them strong nuclear localization of GHRH was also revealed. In situ hybridization indicated the presence of GHRH mRNA in six cases, all characterized as positive for GHRH immunoreactivity. CONCLUSION: GHRH is expressed in a subset of endometrial tumors, of the endometrioid type in particular. A paracrine/autocrine role for GHRH in the development of the disease should be considered.

WT1 immunoreactivity in uterine papillary serous carcinomas is different from ovarian serous carcinomas.

WT1 diffusely stains most ovarian serous carcinomas; reactivity of uterine papillary serous carcinomas has not been evaluated. We studied WT1 expression in 13 International Federation of Gynecology and Obstetrics stage 1 and 5 stage 3 or 4 uterine papillary serous carcinomas without ovarian metastases and compared their reactivity with the WT1 staining of 30 ovarian serous carcinomas. WT1 reactivity was evaluated with the C19 and 6F-H2 antibody clones. All 18 uterine papillary serous carcinomas were nonreactive for WT1. The nonovarian metastases of the 5 high-stage uterine papillary serous carcinomas also were nonreactive for WT1. In contrast, 29 (97%) of 30 ovarian serous carcinomas were reactive for WT1. WT1 reactivity in an unknown primary serous carcinoma would suggest it is from a nonuterine site. The mechanisms underlying these findings are unknown. They raise the possibility of genetic differences between the 2 morphologically similar neoplasms.

Oncocytic biliary cystadenocarcinoma is a form of intraductal oncocytic papillary neoplasm of the liver.

Biliary cystadenocarcinoma with oncocytic differentiation was first reported in 1992. This is a report of a second case. The patient (a 71-year-old man) was admitted to our hospital complaining of abdominal fullness. Multicystic lesions were identified in the left hepatic lobe radiologically. The patient died of peritoneal dissemination of carcinoma 20 months later. At autopsy, the tumor of the left hepatic lobe was found to be composed of adjoining multiple cystic lesions and a solid lesion with infiltration of the hepatic hilus and peritoneal dissemination. Histologically, the multicystic lesions were covered by papillary neoplastic epithelial cells with an eosinophilic granular cytoplasm resembling that of oncocytes and a fine fibrovascular core. The cyst wall was fibrous, but there was no mesenchymal stroma. In the solid lesion and infiltrated areas, acidophilic and granular carcinoma cells formed small glandular or solid cord patterns with much mucin secretion (mucinous carcinoma). Immunohistochemically, carcinoma cells of both components were found to contain many mitochondria and showed the phenotypes of hepatocytes and cholangiocytes. Interestingly, the intrahepatic biliary tree also was invaded by carcinoma cells. This may be a case of intraductal oncocytic papillary neoplasm of the left hepatic lobe followed by secondary cystic dilatation of the affected bile duct.

Papillary serous carcinoma of peritoneum: case study and review of the literature on the differential diagnosis of malignant peritoneal tumors.

The distinction between malignant mesothelioma and other malignant neoplasms diffusely involving the peritoneum is important for proper patient treatment. The extra-ovarian peritoneal serous papillary carcinoma is a rare, primary, multicentric peritoneal tumor that is morphologically identical to ovarian serous carcinoma of equivalent grade, but can spare or minimally involve the ovaries. We report such a tumor in a 65-year-old female who had abdominal swelling, ascites with positive cytology and a high grade of nuclear atypia in malignant cells as well as elevated serum CA125. Exploratory laparotomy findings of intrabdominal carcinomatosis were not accompanied by any evident primary site; so the diagnosis of a primary papillary serous neoplasia of the peritoneum was strongly considered. Since the amount of residual disease may be an important prognostic determining factor in primary papillary serous carcinoma of the peritoneum, the patient was debulked to no macroscopic disease and was then given platin-based chemotherapy. The tumor's differential diagnosis from malignant mesothelioma was based, apart from morphologic criteria, on the tumor's immunoreactivity to MOC-31, Ber-EP4 and TAG-72, as well as on the lack of immunostaining for keratin 5/6 and calretinin. Differential diagnosis from ovarian cancer was possible only after the pathological examination of the surgically resected ovaries; the tumor showed minimal superficial invasion of the ovarian cortex.

Clinical and molecular comparison between borderline serous ovarian tumors and advanced serous papillary ovarian carcinomas.

The aim of this study was to characterize the clinical and molecular markers of borderline serous ovarian tumors (BSOT), and to study their expression in the progression from benign lesions to advanced serous papillary ovarian carcinomas (SPOC). The clinical records of 20 patients with BSOT and 22 patients with SPOC were reviewed. Specimens from all these cases and from six benign ovarian serous cystadenomas were evaluated for expression of estrogen receptors (ER), progesterone receptors (PR), p53. HER-2/neu and Ki-67 by immunohistochemical techniques. The mean patient age and the age at menarche differed significantly between the compared groups of BSOT and SPOC (p=0.0006 and p=0.0014, respectively). No difference was observed comparing the other clinical parameters. The immunohistochemical analysis demonstrated a significant increase in the expression of ER (100% vs 72.7%), and a significant decrease in the immunoreactivity for p53 (0% vs 45.4%) and Ki-67 (2% vs 26.8%) in cases of BSOT compared with those of SPOC (p=0.007, p=0.0003 and p=0.012, respectively). No significant difference was demonstrated comparing the expression of PR and HER-2/neu. The immunostaining of benign ovarian serous cystadenoma specimens did not differ significantly from immunoreactivity observed in cases of BSOT. According to immunohistochemical analysis, BSOT had much more in common with benign serous tumors than with SPOC. The main difference between BSOT and SPOC was regarding the overexpression of p53 and Ki-67.