C. James Sung

α and β subunits of inhibin/activin as sex cord-stromal differentiation markers

Inhibins (α and β heterodimers) and activins (β homodimers) are related peptides with opposing biologic action on gonadotropin regulation. They serve as components of the pituitary-gonadal feedback system. Although sexcord stromal tumors can usually be distinguished from ovarian epithelial tumors or their metastases by morphology or by using antibodies against intermediate filaments, the diagnosis remains difficult in rare situations in such cases as sarcomatoid granulosa-theca cell tumors, ovarian small cell carcinomas, or soft-tissue sarcomas. A total of 28 sex cord-stromal tumors of the ovary and 43 non-sex cord-stromal tumors were immunohistochemically evaluated for the presence of α and β subunits of inhibin and activin. For comparison, 10 normal adult gonads including seven ovaries with hilar regions and three testes also were examined. Immunoreactivity for both α and β subunits of inhibin/activin was identified in both non-neoplastic and neoplastic granulosa, Sertoli, Leydig, hilar and luteinized theca cells, with the strongest immunoreactivity in Leydig and hilar cells. One of three Sertoli-Leydig cell tumors that showed a sarcomatoid growth pattern and one sex-cord tumor with annular tubules also were immunoreactive for both subunits. For non-sex cord stromal-derived ovarian tumors, α subunit immunoreactivity was negative in all but two of five ovarian mucinous tumors. Weak immunoreactivity for β subunit was found in most ovarian surface epithelial carcinomas, two of four colonic, and one of three pancreatic carcinomas. No immunostaining was found in nonspecialized gonadal stromal or interstitial cells, thecal cells, germ cells, ovarian small cell carcinomas, carcinoid tumors, dysgerminomas, or leiomyosarcomas. Immunostaining of α subunit (inhibin α), but not of β subunit could serve as a sex cord-stromal differentiation marker because α subunit alone is largely confined to sex cord-stromal lesions with the exception of some ovarian mucinous tumors. Further studies are needed to define the usefulness of this sex cord-stromal differentiation marker in the practice of surgical pathology. Coexpression of α and β subunits in sex cord-stromal elements suggests that dimeric inhibin is expressed in these cells.

ThinPrep Pap Test promotes detection of glandular lesions of the endocervix.

The objectives of this study were to evaluate 1) the detection rate of atypical glandular cells of undetermined significance of endocervical cell type (AGUS‐EC) and 2) the correlation between AGUS‐EC on cytology and biopsy results using the conventional Papanicolaou (Pap) smear test vs. the ThinPrep® Pap test (TPPT). Cervical‐vaginal samples processed by the conventional Pap smear for 11 mo in 1996–1997 were identified, as were TPPTs collected for the same interval in 1997–1998. Biopsy results were compared after a 9‐mo follow‐up for both groups. There were 112 AGUS‐EC cases from 82,754 conventional Pap smears (detection rate, 0.14%) compared with 58 cases from 82,252 TPPTs (detection rate, 0.07%) (P < 0.01). Biopsies were available in 72 of 112 patients from the conventional Pap smear group and 35 of 58 patients from the TPPT groups. Five dysplastic glandular lesions/AIS were diagnosed by biopsy in the 35 patients (14.3%) from the TPPT group, compared with 2 of the 72 patients (2.8%) from the conventional Pap smear group (P < 0.05). There were no statistically significant differences between other follow‐up diagnoses for the two methods. The use of TPPT resulted in fewer cases of AGUS‐EC and better correlation with histology. The TPPT appears to be as sensitive as and more specific than the conventional Pap smear for detection of endocervical glandular lesions. Diagn. Cytopathol. 23:19–22, 2000.

Reference Values for Second Trimester Fetal and Neonatal Organ Weights and Measurements

To establish accurate reference ranges for the entire second trimester, we documented organ weights, body weight, and linear measurements for 597 fetuses and neonates with gestational ages ranging from 12 to 26 wk. We determined the mean and standard deviation for weights and measurements at each week of gestation using the StatView™ SE + Graphics statistical program. The analyses revealed a linear correlation between the gestational age and, respectively, the toe-heel length, crown-rump length, and crown-heel length. Body and organ weights increase at varying rates throughout the second trimester. The data correlate well with weights and measurements previously published for the latter half of the second trimester, and extend these reference ranges to encompass the entire second trimester.

Minor serous and clear cell components adversely affect prognosis in ''mixed-type'' endometrial carcinomas: a clinicopathologic study of 36 stage-I cases.

Most endometrial carcinomas contain only 1 Müllerian cell type although the presence of 2 or more cell types within 1 tumor, for example a predominantly low-grade endometrioid carcinoma with a minor component (arbitrarily defined as 30% or less) of high-grade serous and/or clear cell carcinoma, is not uncommon. The current study attempts to evaluate whether the presence of minor serous or clear cell components exerts an adverse effect on the prognosis in stage-I endometrial carcinomas of ‘‘mixed-type.’’ The study cases include 22 cases of stage-I endometrioid carcinoma with a minor component of serous carcinoma and 14 cases of endometrioid carcinoma with a minor component of clear cell carcinoma. Minor components were arbitrarily defined as representing anywhere between 5% and 30% of the total tumor. The study cases were compared with 56 cases of histologically pure age-matched and stage-matched endometrioid carcinomas, 6 pure serous carcinomas, and 13 pure clear cell carcinomas. All study and control cases were fully staged. Treatment history and outcome status were obtained and follow-up ranged from 56 to 140 months. Our study suggests that the presence of minor components of serous and clear cell carcinoma, defined as between 5% and 30%, within a mixed-type endometrial carcinoma appears to adversely influence the long-term survival of stage-I tumors, although a larger study is needed to corroborate our findings.

Long-term follow-up of vulvar cancer patients evaluated with sentinel lymph node biopsy alone

OBJECTIVE The objective of this study was to examine SLN evaluation alone in women with squamous cell carcinoma (SCC) of the vulva and evaluate the inguinal recurrence and complication rates. METHODS An IRB approved prospective study enrolled patients with SCC of the vulva. Peritumoral injection of Tc-99 sulfur colloid and blue dye was used to identify SLNs intraoperatively. Patients with negative SLN for metastasis were followed clinically without further treatment. Patients with metastasis to a SLN underwent full groin node dissection followed by standard treatment protocols. RESULTS A total of 73 women were enrolled onto protocol with 69 patients undergoing SLN dissection. Mean age was 66.9years (range: 29-91) with 47 stage I, 12 stage II, 9 stage III, 2 stage IV and 3 unstaged patients. SLN dissections were successful in 63 patients. Of the 111 groins evaluated with a SLN dissection 93% had a SLN identified with an average of 2 SLN per groin. There were 92 groins with negative SLN and 11 groins with positive SLN. 57 patients had negative SLN and underwent conservative management with the median follow-up of 58.3months. Three patients experienced groin recurrences (2 unilateral, 1 bilateral) for a recurrence rate of 5.2% (3/57). The complication rate for the inguinal incisions was 17.5% (1 cellulitis, 1 abscess, 2 lymphoceles, 5 lymphedema and leg pain). CONCLUSIONS Isolated SLN dissection alone has a low inguinal recurrence rate with decreased complications and should be considered as an option for women with SCC of the vulva.

Overexpression of p53 is correlated with stromal invasion in extramammary Paget’s disease of the vulva

Molecular alterations that are associated with clinicopathological features of extramammary Pagets disease of the vulva (PDV) are poorly understood. Consequently, we have investigated whether a correlation exists between overexpression of p53 protein and various clinicopathologic features of PDV. Our study group comprises 10 primary noninvasive PDVs, 3 primary PDVs with minimal invasion, and 1 primary PDV with frank invasion. Recurrence in the form of noninvasive PDV was seen in 4 patients with previously noninvasive PDVs and in 1 patient who previously had PDV with minimal invasion. Metastases to the inguinal lymph nodes were associated with the 1 PDV with frank invasion and 1 of the PDVs with minimal invasion. An immunohistochemical study of p53 expression was performed on paraffin-embedded tissue. Negative p53 immunostaining was seen in all of the primary noninvasive PDVs as well as their recurrences. Positive p53 immunostaining was observed in the invasive as well as the intraepidermal components of all of the primary PDVs with invasion, the metastatic tumors in the inguinal lymph nodes, and the recurrent PDV associated with prior invasion, indicating a possible role of p53 in the progression of PDV. To our knowledge, our observation of p53 overexpression in the intraepidermal component of PDVs associated with invasion is the first to be reported in the literature. This observation may prove helpful in identifying stromal invasion in small biopsies. We also report for the first time an association between high nuclear grade in PDV and the propensity for inguinal lymph node metastasis.

Evaluation of a New Selective Enrichment Broth for Detection of Group B Streptococci in Pregnant Women

ABSTRACT Studies at two Brown Medical School-affiliated hospitals were undertaken to evaluate a new selective broth medium (GBS broth) and to compare it to the LIM broth currently used to culture for group B streptococci. Beta-hemolytic group B streptococci produce a carotenoid pigment that turns GBS broth an orange color. From a total of 580 pregnant women, duplicate vaginal-rectal swabs were collected at 35 to 37 weeks of gestation and cultured for group B streptococci, using either LIM broth (a selective broth containing antibiotics) or GBS broth for enrichment. Specimens were either transported to the laboratory or immediately placed in the respective enrichment broths and delivered to the laboratory. GBS broth medium had sensitivity, specificity, and positive and negative predictive values of 87.8, 100, 100, and 95.1% when planted in the laboratory and 90.3, 100, 100 and 97.6%, respectively, when inoculated at bedside. Use of GBS broth would satisfy Centers for Disease Control and Prevention requirements and would provide faster, more-sensitive, and cost-effective detection of group B streptococci in pregnant women.

Maspin expression in CIN 3, microinvasive squamous cell carcinoma, and invasive squamous cell carcinoma of the uterine cervix

Maspin is a serine protease inhibitor with tumor suppression activity. It is expressed in normal breast and prostate tissue but is downregulated or absent in breast and prostate tumors. Recent reports have shown that decreased expression is associated with a greater propensity for metastasis in oral squamous cell carcinomas. We know that some high-grade cervical intraepithelial neoplasia progress to invasive carcinomas while others either persist at the same degree of atypia or regress. The pattern of maspin expression in cervical intraepithelial neoplasia-grade 3, microinvasive squamous carcinomas and overtly invasive squamous cell carcinomas of the uterine cervix was studied to determine the relationship between the extent of maspin expression and the progression of cervical intraepithelial neoplasia to squamous cell carcinoma. In total, 36 cases were evaluated: 18 cases of cervical intraepithelial neoplasia-grade 3, seven cases of microinvasive squamous cell carcinoma and 11 cases of invasive squamous cell carcinoma. A monoclonal antibody was used on paraffin-embedded tissues. Immunoreactivity was scored semiquantitatively using a scale of 0–3. The sums of the scores of the different groups were compared using the Mann–Whitney U-test. A significant decrease in maspin scores was noted between cervical intraepithelial neoplasia-grade 3 vs invasive squamous cell carcinoma (P<0.005), microinvasive squamous cell carcinoma vs invasive squamous cell carcinoma (P<0.05), and cervical intraepithelial neoplasia-grade 3 vs tumor emboli (P<0.005). Although not statistically significant, scores of cervical intraepithelial neoplasia-grade 3 associated with invasive squamous cell carcinoma were lower compared to that cervical intraepithelial neoplasia-grade 3 without invasive squamous cell carcinoma. These findings suggest that maspin likely plays a role in disease progression from in situ to invasive carcinoma. Virtual absence of maspin immunopositivity in tumor emboli indicates that maspin may also play a role in metastasis.

The expression of selenium-binding protein 1 is decreased in uterine leiomyoma

BackgroundSelenium has been shown to inhibit cancer development and growth through the mediation of selenium-binding proteins. Decreased expression of selenium-binding protein 1 has been reported in cancers of the prostate, stomach, colon, and lungs. No information, however, is available concerning the roles of selenium-binding protein 1 in uterine leiomyoma.MethodsUsing Western Blot analysis and immunohistochemistry, we examined the expression of selenium-binding protein 1 in uterine leiomyoma and normal myometrium in 20 patients who had undergone hysterectomy for uterine leiomyoma.Results and DiscussionThe patient age ranged from 34 to 58 years with a mean of 44.3 years. Proliferative endometrium was seen in 8 patients, secretory endometrium in 7 patients, and atrophic endometrium in 5 patients. Two patients showed solitary leiomyoma, and eighteen patients revealed 2 to 5 tumors. Tumor size ranged from 1 to 15.5 cm with a mean of 4.3 cm. Both Western Blot analysis and immunohistochemistry showed a significant lower level of selenium-binding protein 1 in leiomyoma than in normal myometrium. Larger tumors had a tendency to show a lower level of selenium-binding protein 1 than smaller ones, but the difference did not reach a statistical significance. The expression of selenium-binding protein 1 was the same among patients with proliferative, secretory, and atrophic endometrium in either leiomyoma or normal myometrium. Also, we did not find a difference of selenium-binding protein 1 level between patients younger than 45 years and older patients in either leiomyoma or normal myometrium.ConclusionsDecreased expression of selenium-binding protein 1 in uterine leiomyoma may indicate a role of the protein in tumorigenesis. Our findings may provide a basis for future studies concerning the molecular mechanisms of selenium-binding protein 1 in tumorigenesis as well as the possible use of selenium in prevention and treatment of uterine leiomyoma.

High-grade serous carcinoma arising in a low-grade serous carcinoma and micropapillary serous borderline tumour of the ovary in a 23-year-old woman.

but so far no data about this transcriptional factor have been published for malignant plasma cells. FOXP1 is considered a potential therapeutic target in a variety of cancers. Koon et al. wrote a review in 2007 about FOXP1 changes in gastrointestinal, lung, head, neck and breast cancer, genitourinary malignancies and B-cell lymphomas. They stated that FOXP1-directed therapy could have significant potential, but that many data about FOXP1 function are still missing. It is still not clear whether FOXP1 acts as an oncogene or tumour suppressor, or if there are other, as yet uninvestigated malignancies in which it has prognostic value. Our data describe a case of MM with hyperploidy, multiple IgH translocations and FOXP1 expression; to our knowledge this is the first reported case with six translocated genes as well as the first reported case of FOXP1 expression in malignant plasma cells. It demonstrates the need for further investigation into the prognostic value of FOXP1 protein expression in MM.