The association of the microcystic, elongated and fragmented (MELF) invasion pattern in endometrial carcinomas with deep myometrial invasion, lymphovascular space invasion and lymph node metastasis.

The purpose of this study was to investigate the frequency of microcystic, elongated and fragmented (MELF) pattern of invasion in endometrioid endometrial adenocarcinomas (EA) and its association with prognostic factors. Stained tissue sections from 121 cases of EA (total hysterectomy and pelvic, with or without para-aortic, lymphadenectomy specimens) were reviewed to identify cases showing MELF-type invasion. The prognostic factors of low tumour grade, deep myometrial invasion (MI), cervical stromal involvement, lymphovascular space invasion (LVSI), lymph node (LN) metastasis and advanced clinical stage were more frequently observed in MELF-positive cases (p < 0.05). Thus, MELF-positive cases had an increased frequency (28/121) of these prognostic factors, which has implications in routine clinical practice, as it signals the importance of recognising MELF pattern invasion. In univariate analysis, MELF positivity, deep MI, cervical stroma involvement and LVSI were significantly related to LN metastasis (p < 0.05). However, in multivariate analysis, only MELF pattern invasion and cervical stroma involvement were independent factors for LN metastasis. Nevertheless, further studies are needed to evaluate the clinical significance of MELF pattern of invasion in endometrial adenocarcinoma.

Ex vivo intra-arterial methylene blue injection in the operation theater may improve the detection of lymph node metastases in colorectal cancer.

INTRODUCTION: Lymph node (LN) assessment after colorectal cancer resection is fundamentally important for therapeutic and prognostic reasons. LN positivity is an indication for adjuvant treatment. This study aimed to investigate whether immediate postoperative intra-arterial methylene blue (MB) injection (MBI) into colorectal cancer specimens by a surgeon in the operating room could improve the rate of total LN and metastatic LN recovery for pathological examination. MATERIALS AND METHODS: Seventy-three consecutive patients prospectively enrolled between January 2011 and December 2013 were assigned to the methylene blue (MB)-stained group and compared with 107 controls in the unstained group. RESULTS: The median number and range values of metastatic LNs, the number of LNs <0.5 cm, the total number of LNs harvested, and the number of cases with LN metastasis were significantly different between the MB-stained and MB-unstained groups (p = 0.016, p = 0.010, p = 0.025, and p = 0.006 respectively). CONCLUSIONS: Immediate MBI (fresh, unfixed samples) by a surgeon in the operating room may result in a significant increase in the number of metastatic LNs diagnosed and the number of cases with positive LNs. Shifting of the injection from the pathology laboratory to the operation theater would be a good alternative whenever the operation theater is not the area located as the pathology department.

The association of the cribriform pattern with outcome for prostatic adenocarcinomas.

With the revision of the Gleason system at the 2005 International Society of Urological Pathology Consensus Conference, there was consensus that most cribriform glands should be classified as pattern 4. There is now increased understanding that invasive cribriform carcinoma is a relatively aggressive disease. This study was based on 233 radical prostatectomy (RP) specimens collected at the Department of Pathology, Umraniye Education and Research Hospital, from 2006 to 2013. We assessed the cribriform foci associated with the more definitive patterns 3, 4, and 5 elsewhere on the RP specimens and evaluated the association of the presence of cribriform pattern (CP) with biochemical prostate-specific antigen recurrence (BPR). In Cox regression model, taking into account the Gleason score (GS), pathologic stage, surgical margin (SM) status, presence of a CP, and preoperative prostate-specific antigen (PSA), a positive SM, and the presence of a CP were independent predictors of BPR after RP. We observed BPR more frequently in GS 3+3 cases with a CP than in those without a CP (p=0.008). There was no significant difference in BPR status for cases with GS 3+4, 4+3, 4+5, and 5+4 when the patients were stratified by the presence of a CP. On the basis of these data, we suggest that the classification of CP into Gleason pattern 4 has value in predicting BPR status after RP. However, as many of these modifications are empirical and supported by only a few studies, long-term follow-up studies with clinical endpoints are necessary to validate these recommendations.

Cytohistological correlation of endocervical gland involvement with high-grade squamous intraepithelial lesions.

BACKGROUND: Diagnosis of endocervical glandular involvement by high-grade squamous intraepithelial lesion (HSIL-EGI) on Papanicolaou (Pap) smears can affect the clinical management of patients. AIM: The cytological criteria for the diagnosis of HSIL-EGI are described and the accuracy of this diagnosis was investigated. MATERIALS AND METHODS: Seventeen patients diagnosed with HSIL-EGI and 40 patients with diagnosis of HSIL on Pap smears with follow-up cone or loop electrocautery excision procedure (LEEP) biopsies were included in the study. The following criteria were evaluated for the cytological diagnosis of HSIL-EGI: atypical cells with definite features of HSIL, three-dimensional atypical squamous cell clusters (TDCs) with attached benign endocervical epithelium, finger-like TDCs covered with intact epithelium on most sides, which represent the finger-like invaginations of the endocervical glandular area involved by HSIL, and the absence of cytological findings of in situ adenocarcinoma of the cervix. RESULTS: On subsequent histopathological evaluation, 16 of 17 (94.1%) patients with a cytological diagnosis of HSIL-EGI and 17 of 40 (42.5%) patients with HSIL exhibited endocervical glandular involvement (P < 0.001, sensitivity: 48.5%, specificity: 95.8%, positive predictive value: 94.1%, negative predictive value: 57.5% and accuracy: 68.4%). CONCLUSION: Diagnosis of HSIL-EGI may be possible on Pap smears with a high positive predictive value and specificity but low sensitivity, possibly due to cytological sampling limitations. To clarify the results of the present study, more extensive studies with a particular emphasis on the sampling of the endocervical glandular area for cytological evaluation of the cervix are needed.

Primary serous carcinoma of the fallopian tube with synchronous cervical epidermoid carcinoma in situ: a case report.

Primary carcinoma of the fallopian tube is rare and its preoperative diagnosis difficult due to the lack of specific symptoms. In this report we present a rare case of primary carcinoma of the fallopian tube with synchronous cervical high-grade squamous intraepithelial lesion (HSIL). A 39-year-old women was admitted to our hospital for routine gynecological examination and underwent surgery because of the finding of HSIL on a routine papanicolaou smear. The histological diagnosis on cervical biopsy and conization material were of cervical intraepithelial neoplasia III (CIN III). Serous carcinoma of the fallopian tube was incidentally found during a planned hysterectomy operation. Postoperatively the patient received six cycles of adjuvant chemotherapy (carboplatin and paclitaxel) and is still under routine control. In conclusion, the genital tract should be examined in detail in case of any existence of a primary genital tumor and CA125 should be added to the examination.

Peritoneal tuberculosis simulating advanced ovarian carcinoma: is clinical impression sufficient to administer neoadjuvant chemotherapy for advanced ovarian cancer?

Peritoneal tuberculosis mimics advanced ovarian cancer because of the similarities in clinical signs and symptoms such as ascites, pelvic and abdominal pain and mass, and elevation of serum CA125 level. We have presented four cases of peritoneal tuberculosis that underwent exploratory laparotomy for suspected advanced ovarian cancer during a 3-year period. Definitive diagnosis of tuberculosis was performed at laparotomy in all the cases. The frozen-section analysis seems to be the gold standard in the differential diagnosis. In view of these data, clinical diagnosis of advanced ovarian cancer is not sufficient for administering neoadjuvant chemotherapy. Cytologic or pathologic findings must be consistent with ovarian cancer for candidates who are being considered for neoadjuvant chemotherapy.

Metastatic ovarian carcinoma one year after surgical removal of colon carcinoma during pregnancy: a case report.

Colorectal carcinoma during pregnancy is a very rare event. We presented a woman with metachronous metastatic ovarian tumor existing 1 year after surgical removal of perforated sigmoid colon carcinoma encountered during cesarean section of woman of 36-week gestation for fetal distress. Pregnant women with suspicious abdominal mass should be evaluated for a possible colorectal carcinoma even in the absence of any other gastrointestinal symptoms associated with it and undergo rectal examination and sigmoidoscopy. In addition, as synchronous and metachronous ovarian metastases are common in these patients, ovaries must be evaluated carefully by bisection during operation for possible metastasis, and in women who do not have a desire for fertility, prophylactic oophorectomy seems an appropriate treatment modality for resecting synchronous metastasis and preventing future metastasis.

Mucoepidermoid variant of adenosquamous carcinoma arising in ovarian dermoid cyst: a case report and review of the literature.

A 40-year-old woman with mucoepidermoid variant of adenosquamous carcinoma arising in dermoid cyst in left ovary is presented. The patient was staged as IC. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and pelvic and para-aortic lymph node sampling were carried out. The disease recurred in postoperative 12th month. To our best knowledge, this is 12th case of adenosquamous carcinoma in dermoid cyst and third case of mucoepidermoid variant of adenosquamous carcinoma in the literature.

Large-cell neuroendocrine carcinoma of the cervix associated with cervical-type invasive adenocarcinoma: a report of case and discussion of histogenesis.

A case of cervical large-cell neuroendocrine carcinoma with mucinous-type cervical adenocarcinoma component adjacent to it is presented, and its histopathogenesis and clinical course are discussed under the light of the literature.

Uterine liposarcoma in a young woman: a case report.

Liposarcoma of uterus is a very rare neoplasm encountered generally in the sixth or seventh decade of life. We reported the eighth case of uterine liposarcoma with extension to broad ligament in a 23-year-old woman who presented with pelvic pain, dysuria, and rapidly enlarging pelvic mass. During laparotomy, the mass was detected to be originated from the uterine cervix. In frozen section, no definitive diagnosis was established, and for preservation of fertility, extirpation of the mass was performed. The histopathologic examination of the specimen revealed liposarcoma. The tumor cells were diffusely and intensively immune reactive for vimentin and S-100, and negative for smooth muscle actin, desmin, h-caldesmon, pan cytokeratin, and CD10. Staining with periodic acid and Schiff, alcian blue, mucicarmine, and epithelial membrane antigen (EMA) were negative. No recurrence was detected in the postoperative seventh month. Present case is the youngest patient with uterine liposarcoma and also the first case detected in reproductive period.

Atypical glandular cells: improvement in cytohistologic correlation by the 2001 Bethesda system.

The objective of this article was to evaluate clinical significance of glandular atypia on Papanicolaou smear, to compare the Bethesda system (TBS) 2001 with the 1991 revision, and to determine whether there is any improvement in the cytohistologic correlation by the new system. Cytology files of 18,955 patients were reviewed for diagnosis of atypical glandular cells of undetermined significance (AGUS), and histopathology files were searched. Cervical smears of these patients were reclassified according to TBS 2001. Of the 18,955 specimens, 89 (0.46%) were diagnosed as AGUS. Of these 89 women, 76 (85.3%) accepted the follow-up protocol of our hospital. In reevaluation according to TBS 2001, 31 specimens were reevaluated as atypical glandular cells (AGC) and 3 were reevaluated as adenocarcinoma in situ, 8 as AGC with concomitant squamous cell abnormalities, 1 as atypical squamous cells that cannot exclude high-grade squamous intraepithelial lesions, and 33 as negative. Thirty-one (93.9%) of these 33 negative cases were in the AGUS-reactive category in the initial examination. The difference between the rates of the malignant pathologies in the AGUS (25%, 19/76) and in the AGC (42.8%, 18/42) categories was significant (chi(2)= 4.0, P= 0.04). The new terminology of AGC is more likely to suggest a clinically significant lesion than TBS 1991. Repeated cytologic testing during follow-up seems to be unacceptable.

Utility of MIB-1 and estrogen and progesterone receptor in distinguishing between endometrial stromal sarcomas and endometrial stromal nodules, highly cellular leiomyomas.

It is difficult to differentiate between an endometrial stromal nodule (ESN) and endometrial stromal sarcoma (ESS) in curettage specimen, and the recommended therapy of endometrial stromal neoplasm is hysterectomy. If we could discriminate ESS from ESN in curettage specimens, there would be an opportunity to treat ESN by local excision rather than by hysterectomy. We analyzed MIB-1 and estrogen and progesterone receptor (ER/PR) expression in a retrospective series of 8 ESSs, 7 ESNs, and 17 highly cellular leiomyomas obtained from hysterectomy specimens. ESSs expressed MIB-1 more frequently than ESNs (P < 0.05), and ESSs had a tendency to express ER less frequently than ESNs (P= 0.08). We observed that in spite of showing MIB-1 expression to some extent, highly cellular leiomyomas usually could not reach ESSs' level and frequency of MIB-1 expression in the current study. Although MIB-1 and ER appear to be promising markers in the differential diagnosis of ESSs, a larger study would be necessary to confirm their validity.

Atypical squamous cells: improvement in cytohistological correlation by the 2001 Bethesda System.

PURPOSE OF INVESTIGATION: To evaluate the advantages of the 2001 Bethesda System over the 1991 Bethesda System in the management of atypical squamous cells. METHODS: The cytology files of the 8,748 patients were reviewed for diagnosis of atypical squamous cells of undetermined significance (ASCUS) at Zeynep Kamil Hospital. Seventy-two of the 259 smear specimens with the diagnosis of ASCUS were reviewed and reclassified according to Bethesda 2001. RESULTS: Of the 8,748 specimens, 259 (2.96%) were diagnosed as ASCUS. In re-evaluation of the 72 specimens according to the 2001 Bethesda system, the number of cervical smears with a diagnosis of atypical squamous cells (ASC) decreased to 21 in number. Of the 21 cervical smears with an ASC category, eight patients (38.1%) had high-grade intraepithelial squamous lesions (HSIL) and six (28.6%) had low-grade intraepithelial squamous lesions (LSIL) in histopathological specimens. The detection rates of squamous abnormalities (chi2 = 24.79, p < 0.0001) and high-grade squamous abnormalities (chi2 = 8.31, p = 0.0039) were significantly higher according to Bethesda 2001. CONCLUSION: The 2001 Bethesda System seems to reduce the number of cervical smear diagnoses of ASC, without causing any impairment in the diagnosis of HSIL thus decreasing the number of unneccesary interventions like cervical biopsy and decreasing the cost, inconvenience, anxiety and discomfort.

Reporting of "LSIL with ASC-H" on cervicovaginal smears: is it a valid category to predict cases with HSIL follow-up?

Recently it has been shown that there is a 15-30% risk of associated cervical intraepithelial neoplasia (CIN 2-3 or greater) for a low-grade squamous intraepithelial lesion (LSIL) diagnosis. We tried to define a subgroup of "LSIL with atypical squamous cells of undetermined significance. High-grade squamous intraepithelial lesion (LASC-H)" in cervicovaginal screening which may aid in predicting the cases associated with high risk cannot be ruled out. In the years between 2001 and 2003 a total of 21,342 cervicovaginal smears were evaluated. The smears with pure LSIL and LASC-H diagnosis which had histologic follow-up were selected. The cases with diagnosis of LASC-H contained numerous typical cells of LSIL and only a few cells with features suggesting high-grade squamous intraepithelial lesion (HSIL). Eight (61%) of 13 cases with a diagnosis of LASC-H but three (11%) of 27 cases with a diagnosis of pure LSIL resulted in CIN 2-3 histology (p < 0.05). Diagnosis of LASC-H may be a valid diagnostic category in distinguishing patients with LSIL that would have HSIL in follow-up.

Immunohistochemical profile of intravenous leiomyomatosis.

To determine the immunohistochemical staining profile of intravenous leiomyomatosis (IVL), we analysed six IVLs and 12 ordinary leiomyomas (LM) for immunoreactivity with a panel of 11 antibodies. All IVLs and LMs reacted with antibodies to alpha-smooth muscle actin (alphasm), h caldesmon, vimentin and progesterone receptor (PR). Five of six IVLs and all LMs reacted with desmin. All IVLs were negative for CD-10. Only one LM exhibited focal CD-10 positivity. Three of six IVLs and nine of 12 LMs showed estrogen receptor expression. All IVLs and LMs showed immunnegativity with MIB-1 and inhibin. There were not any significant differences between immunoreactivity patterns of IVL and LM for asm, desmin, h caldesmon, CD-10, MIB-1 and PR. We conclude that, although they appear to be useful markers in differentiating IVL from ESS and LMS, a larger study also including ESS and LMS would be necessary to confirm their validity.

Stromomyomas of the uterus-- importance of total circumferential evaluation of the margin.

Four stromomyomas were extensively dissected to represent the entire circumference of the uterus on sequential histologic sections. In all cases the smooth muscle component was extensive, and irregular interdigitation of stromal neoplasia with a smooth muscle component made evaluation of the margin difficult. It was impossible to determine where the smooth muscle component of the neoplasm ended and where peritumoral normal myometrium began. This makes the detection of vascular invasion more important. At the end of a thorough evaluation of sections, large vessel invasion was found on the circumference of three stromomyomas in a particular foci of the margin. Extensive circumferential evaluation of the margin has been evaluated as a promising procedure to allow effective distinction of stromomyomas with focal angioinvasion.

The value of epithelial membrane antigen overexpression in hyperplastic and malignant endometrium and its relationship with steroid hormone receptor expression.

The aim of this study was to evaluate the value of epithelial membrane antigen overexpression (EMA OE) in benign, hyperplastic and neoplastic endometrium and to analyze its association with estrogen and progesterone receptors (ER, PR) immunohistochemistry, tumor grade and myometrial invasion in patients with endometrial carcinoma (EC). The OE of EMA was analysed immunohistochemically in nine patients with benign endometrium (BE), in 18 patients with atypical complex endometrial hyperplasia (ACH) and in 29 patients with EC. EMA OE was present in 13 of 29 patients (44.8%) with EC, in two of 18 patients (11.1 %) with ACH, and in none of nine patients with BE (p < 0.05). EMA OE of endometrial carcinoma was statistically correlated with the International Federation of Gynecology and Obstetrics (FIGO) grade (G1 vs G2 and G3, p < 0.05) and depth of myometrial invasion (< 1/2 vs > 1/2, p < 0.05). EMA OE was significantly associated with PR negativity (p < 0.001). However it did not show any association with ER immunohistochemistry (p = 0.14). PR immunohistochemistry had significant correlations with FIGO grade (p < 0.001) and depth of myometrial invasion (p < 0.05) but ER loss showed a nearly significant association only with advanced FIGO grade (p = 0.054). In conclusion, EMA shows increased expression as the lesion progresses to malignancy and can also aid discrimination between hyperplastic and neoplastic states. The correlation of imunohistochemical findings with tumor grade and myometrial invasion could help in predicting behavior of the tumor and planning treatment in patients with endometrial carcinoma.

Sclerosing stromal cell tumor of the ovary in pregnancy: a case report.

A rare case of benign ovarian stromal cell tumor during pregnancy is presented. Because of a rapidly growing solid ovarian mass, 6 x 7 cm in diameter, a 21-year-old woman at 14 weeks of gestation was explored via laparotomy. Histopathological diagnosis was sclerosing stromal tumor of the ovary. She had no complaint of menstrual irregularities before pregnancy and there was no clinical or hormonal evidence of active androgenic hormone secretion. Immunohistochemical staining showed positive vimentin, smooth-muscle actin and desmin reactions. Sclerosing stromal tumor is a very rare condition in pregnancy and our case is only the eighth case detected during pregnancy according to the literature.

Estrogen and progesterone expression of vessel walls with intravascular leiomyomatosis; discussion of histogenesis.

We report seven cases of intravenous leiomyomatosis. Growth beyond the uterus occurred in two of the seven cases in the broad ligament. One 21-year-old patient is one of the youngest reported cases in the literature. Five patients had total abdominal hysterectomy with removal of the adnexa and two patients underwent myomectomy. One of the myomectomy cases had abdominal hysterectomy and bilateral salpingo-oophorectomy one year later due to recurrence. The other one was disease free six months after the operation. Vessel walls harboring intravascular tumor were investigated immunohistochemically for Factor VIII, CD 34, estrogen and progesterone receptors with the hope of making the histogenesis of intravenous leiomyomatosis clear. Immunohistochemical analyses of estrogen receptors, progesterone receptors, vimentin, desmin, smooth muscle actin, CD 10 and h-caldesmon were performed on intravascular tumor cells. Endothelial and subendothelial cells expressed none to scant, very weak progesterone and estrogen receptor positivity. Intravascular tumor cells showed weak (10%) to strong (70%) progesterone receptor positivity and weak (10%) to strong (60%) estrogen receptor positivity. These results do not support the hypothesis of a vessel wall origin for intravenous leiomyomatosis.