Zeina Ghorab

Adenomyosis is associated with myometrial invasion by FIGO 1 endometrial adenocarcinoma

Summary: Adenomyosis is commonly seen in hysterectomy specimens for endometrial adenocarcinoma where it could be involved with the tumor. When adenocarcinoma involves adenomyosis, the tumor may remain limited to the adenomyosis or proceeds to invade the adjacent myometrium. The purpose of this study was to investigate whether the risk of myometrial invasion by grade 1 endometrioid adenocarcinoma in cases with cancer-positive adenomyosis is different from that of cases where cancer occurs in the absence of adenomyosis. Forty-six consecutive hysterectomy specimens with International Federation of Gynecology and Obstetrics (FIGO) grade 1 endometrial endometrioid adenocarcinoma involving adenomyosis and 49 consecutive specimens with the same tumor occurring in the absence of adenomyosis were retrospectively studied by 4 experienced gynecologic pathologists. In cases with adenomyosis, myometrial invasion was confirmed by CD10-negative staining around glands with irregular outline surrounded by inflamed desmoplastic stroma. Myometrial invasion was found in significantly more adenomyosis cases (n = 42, 91.3%) than in cases without adenomyosis (n = 38, 77.5%) (&khgr;2 = 4.79, P = 0.03). In 16 cases of the former group, the invasion only occurred from the foci of adenomyosis. Although myometrial invasion in the outer half was more common in the adenomyosis group (n = 16, 34.8%) than in cases without adenomyosis (n = 9, 18.4%), the difference was not statistically significant (&khgr;2 = 3.29, P = 0.07). By involving coexistent adenomyosis, FIGO grade 1 endometrial endometrioid adenocarcinoma is associated with myometrial invasion, probably through increasing the surface area of its interface with the adjacent myometrium. When compared with their counterparts that occur in the absence of adenomyosis, these tumors are significantly more likely to invade the myometrium.

Immunophenotyping of serous carcinoma of the female genital tract

To update the data on the expression of ‘mesothelioma markers’ by serous carcinomas of various sites we have studied cases from ovary (n=56), endometrium (n=37), fallopian tube (n=6), primary peritoneum (n=5) and cervix (n=3) using a panel of antibodies (WT1, P53, estrogen receptors, HER2/neu, D2-40, cytokeratin 5/6 and E-cadherin). Ovarian carcinomas demonstrated D2-40 and cytokeratin 5/6 immunoreactivity in 23.2 and 55.4% of cases, respectively. Endometrial carcinomas demonstrated D2-40 and cytokeratin 5/6 immunoreactivity in 43.2 and 37.8% of cases, respectively. D2-40 staining pattern was predominantly focal; however, strong reactivity was identified in 16.2% of endometrial and 10.7% of ovarian carcinomas. HER2/neu oncoprotein overexpression was demonstrated in 7 of 37 (18.9%) uterine serous carcinomas. In contrast, all the serous carcinomas of the other sites were HER2/neu negative. The proportion of positive cases was significantly different in ovarian vs endometrial carcinomas regarding WT1 (P=0.0458), estrogen receptors (P<0.001) reactivity and HER2/neu overexpression (P=0.0025). D2-40 and cytokeratin 5/6 are expressed in a considerable proportion of serous carcinomas and should be used cautiously in a ‘mesothelioma panel’ in situations where serous carcinoma is in the differential diagnosis. HER2/neu was exclusively overexpressed in serous carcinomas of endometrial origin.

Melan A (A103) is expressed in adrenocortical neoplasms but not in renal cell and hepatocellular carcinomas.

Most adrenocortical neoplasms, renal cell carcinomas, and hepatocellular carcinomas are diagnosed by a combination of clinical and morphologic features. However, occasionally this histologic differential diagnosis requires additional ancillary tests, such as immunohistochemistry. The authors investigated the potential value of A103 in the differential diagnosis of these tumors. Thirty-two adrenocortical neoplasms, 86 renal cell carcinomas, and 57 hepatocellular carcinomas were evaluated by immunohistochemistry using a monoclonal antibody A103 and a standard ABC method. The adrenocortical neoplasms were 21 adenomas and 11 carcinomas. Thirty-one of the 32 adrenocortical neoplasms showed strong and diffuse granular cytoplasmic staining for Melan A. No nuclear reaction was observed. There were no differences in staining patterns between adrenocortical adenomas and carcinomas. With the exception of one clear cell renal cell carcinoma, all non-adrenocortical neoplasms were negative. The authors conclude that A103 is a useful addition to the immunohistochemical panel in the differential diagnosis of adrenocortical neoplasms from both renal cell and hepatocellular carcinomas. This marker, however, does not separate benign from malignant adrenocortical neoplasms.

Her2 Expression in Prostatic Cancer: A Comparison With Mammary Carcinoma

PURPOSE There is growing interest in HER2 and its downstream signaling pathway molecules as treatment targets in human malignancies, including prostatic carcinoma. We used a standard Food and Drug Administration approved HER2 immunohistochemical kit to study HER2 expression in prostate cancer. We compared the results with those reported for mammary carcinoma. MATERIALS AND METHODS For this study we selected 216 specimens obtained from patients who underwent radical prostatectomy for primary untreated prostatic carcinoma. Immunohistochemical staining was performed using the HercepTest kit (Dako Corp., Carpinteria, California) in strict fashion according to the technical and analytical protocols outlined in the kit. RESULTS Of the tumors 33 (15%) were positive for HER2, including 31 (94%) that were only weakly positive (2+). Of the HER2 positive tumors 97% were Gleason grade 7 or higher. Of the 33 positive cases 22 (67%) showed only a focal positive reaction for HER2 in discrete tumor areas. CONCLUSIONS HER2 is expressed in a minority of untreated primary prostatic carcinomas. Unlike in mammary carcinoma, HER2 positivity in prostatic cancer is usually weak in intensity and focal in distribution. While the former casts doubt on the usefulness of HER2 as a potential treatment target for most primary untreated prostatic cancer, the latter phenomenon may lead to false-negative results if the test is performed in small biopsies. Furthermore, HER2 staining of prostatic carcinoma can be technically and analytically reproducible provided that there is strict adherence to the outlined methodologies and interpretation.

Assessment of endometrial sampling as a predictor of final surgical pathology in endometrial cancer

Background:The histology and grade of endometrial cancer are important predictors of disease outcome and of the likelihood of nodal involvement. In most centres, however, surgical staging decisions are based on a preoperative biopsy. The objective of this study was to assess the concordance between the preoperative histology and that of the hysterectomy specimen in endometrial cancer.Methods:Patients treated for endometrial cancer during a 10-year period at a tertiary cancer centre were identified from a prospectively collected pathological database. All pathology reports were reviewed to confirm centralised reporting of the original sampling or biopsy specimens; patients whose biopsies were not reviewed by a dedicated gynaecological pathologist at the treating centre were excluded. Surgical pathology data including histology, grade, depth of myometrial invasion, cervical stromal involvement and lymphovascular space invasion (LVSI) as well as preoperative histology and grade were collected. Preoperative and final tumour cell type and grade were compared and the distribution of other high-risk features was analysed.Results:A total of 1329 consecutive patients were identified; 653 patients had a centrally reviewed epithelial endometrial cancer on their original biopsy, and are included in this study. Of 255 patients whose biopsies were read as grade 1 (G1) adenocarcinoma, 45 (18%) were upgraded to grade 2 (G2) on final pathology, 6 (2%) were upgraded to grade 3 (G3) and 5 (2%) were read as a non-endometrioid high-grade histology. Overall, of 255 tumours classified as G1 endometrioid cancers on biopsy, 74 (29%) were either found to be low-grade (G1–2) tumours with deep myometrial invasion, or were reclassified as high-grade cancers (G3 or non-endometrioid histologies) on final surgical pathology. Despite these shifts, we calculate that omitting surgical staging in preoperatively diagnosed G1 endometrioid cancers without deep myometrial invasion would result in missing nodal involvement in only 1% of cases.Conclusions:Preoperative endometrial sampling is only a modest predictor of surgical pathology features in endometrial cancer and may underestimate the risk of disease spread and recurrence. In spite of frequent shifts in postoperative vs preoperative histological assessment, the predicted rate of missed nodal metastases with a selective staging policy remains low.

In situ localization of follicular lymphoma: evidence for subclinical systemic disease with detection of an identical BCL-2/IGH fusion gene in blood and lymph node

In situ localization of follicular lymphoma: evidence for subclinical systemic disease with detection of an identical BCL-2/IGH fusion gene in blood and lymph node

Expression of TdT in Merkel cell carcinoma and small cell lung carcinoma.

Merkel cell carcinoma (MCC) is an uncommon tumor with indistinct clinical features. The differential diagnosis includes small cell lung carcinoma (SCLC). We characterized the expression of terminal deoxynucleotidyl transferase (TdT) and a panel of immunohistochemical markers in 40 MCC, 30 SCLC, and 6 pulmonary carcinoid tumor (PCT) cases. We used antibodies against TdT, thyroid transcription factor (TTF)-1, cytokeratins (CKs) 7 and 20, chromogranin, and synaptophysin. Immunostaining was recorded semiquantitatively. Of 40 MCC cases, 28 (70%) were positive for TdT, showing, on average, more than 25% of tumor cells reactive with moderate nuclear staining intensity. TTF-1 (1 [3%]), CK7 (2 [5%]), CK20 (35 [88%]), chromogranin (29 [73%]), and synaptophysin (39 [98%]) were expressed in the MCCs. Of the 5 CK20- MCC cases, 4 were positive for TdT. SCLC showed expression of TTF-1 (23/30 [77%]), CK7 (22/30 [73%]), chromogranin (16/30 [53%]), and synaptophysin (22 [73%]) and no CK20 (0%) expression. Of 30 SCLC cases, 2 (7%) were positive for TdT. TdT may be beneficial in rare cases of CK20- MCC and may assist in distinguishing between MCC and SCLC. There is significant immunohistochemical variability and overlap between these 2 tumors.

CDX2 as a marker for intestinal differentiation: Its utility and limitations

CDX2 is a nuclear homeobox transcription factor that belongs to the caudal-related family of CDX homeobox genes. The gene encoding CDX2 is a nonclustered hexapeptide located on chromosome 13q12-13. Homeobox genes play an essential role in the control of normal embryonic development. CDX2 is crucial for axial patterning of the alimentary tract during embryonic development and is involved in the processes of intestinal cell proliferation, differentiation, adhesion, and apoptosis. It is considered specific for enterocytes and has been used for the diagnosis of primary and metastatic colorectal adenocarcinoma. CDX2 expression has been reported to be organ specific and is normally expressed throughout embryonic and postnatal life within the nuclei of epithelial cells of the alimentary tract from the proximal duodenum to the distal rectum. In this review, the authors elaborate on the diagnostic utility of CDX2 in gastrointestinal tumors and other neoplasms with intestinal differentiation. Limitations with its use as the sole predictor of a gastrointestinal origin of metastatic carcinomas are also discussed.

Lymphovascular invasion is a significant predictor for distant recurrence in patients with early-stage endometrial endometrioid adenocarcinoma

To evaluate the value of lymphovascular invasion (LVI) in endometrial endometrioid adenocarcinoma (EEA) as a predictor for distant recurrence, we analyzed the histopathologic features of 513 consecutive cases of nonsurgically staged EEA limited to the uterus. Grade, myoinvasion, cervical involvement, and LVI were evaluated. With a median follow-up of 28 months (range, 2-144 months), 67 cases (13.1%) recurred, 37 (7.2%) had locoregional recurrence, and 30 (5.8%) developed distant recurrence. LVI was identified in 116 cases (22.6%) cases and was the only adverse histopathologic finding in 23 cases; 5 (22%) of the 23 recurred. Multivariate analysis demonstrated a significant association between any type of recurrence and cervical involvement (hazard ratio [HR], 2.760; 95% confidence interval [CI], 1.621-4.698) and LVI (HR, 2.717; CI, 1.568-4.707). Multivariate analysis revealed LVI as the only independent predictor for distant recurrence (HR, 2.841; CI, 1.282-6.297). Studies to examine the role of adjuvant systemic therapy in patients with early-stage disease should be considered.

Low Nuclear Proliferative Activity Is Associated With Nonmetastatic Islet Cell Tumors

CONTEXT Traditional morphologic features of tumor aggression are of limited value in predicting the malignant behavior of endocrine neoplasms. We explored the potential value of nuclear proliferative activity (using Ki-67 immunostaining with semiquantitative scoring) in predicting the clinical behavior of pancreatic islet cell tumors (ICTs), and we correlated this characteristic with hormone expression. OBJECTIVE To evaluate whether Ki-67 immunostaining using a semiquantitative scoring system has value in predicting the clinical behavior of pancreatic ICTs. DESIGN We studied 39 pancreatic ICTs from 39 patients. Twenty-two ICTs did not metastasize in a median follow-up period of 91 months. The remaining 17 neoplasms did produce metastases (8 in liver, 7 in regional lymph nodes, and 2 in peritoneum). Immunohistochemistry was performed using antibodies to Ki-67 and pancreatic hormones (insulin, glucagon, gastrin, somatostatin, pancreatic polypeptide, vasoactive intestinal polypeptide, and corticotropin). A semiquantitative Ki-67 grading system was followed. The nuclear proliferative activity, as determined by a positive reaction for Ki-67, was considered low (<5% of cells staining positively), intermediate (5%-25% of cells staining positively), or high (>25% of cells staining positively). RESULTS The majority of the nonmetastatic ICTs (16 cases, 73%) demonstrated either negative or low staining for Ki-67 (P <.001). Conversely, all metastatic ICTs expressed at least an intermediate-grade reaction. High nuclear proliferative activity was only seen in metastatic neoplasms (3 cases, 17%). There was no relationship between immunoexpression of pancreatic hormones and nuclear proliferative activity by either group of tumors. CONCLUSION An ICT with low nuclear proliferative activity is unlikely to metastasize, whereas high proliferative activity is associated with a metastatic phenotype. Immunohistochemical assessment of Ki-67 using a semiquantitative scoring system is a simple and reliable detection method of cellular proliferative activity in ICTs of the pancreas.