Pain Management During Office Hysteroscopy: A Survey of Hysteroscopists.

OBJECTIVE: Outpatient hysteroscopy can be a painful procedure for some patients and there is still no consensus regarding analgesia use. We evaluated which types and modalities of analgesia are most commonly used in a select group of hysteroscopists. STUDY DESIGN: A 15-item questionnaire was created to assess the use of routine analgesia during office hysteroscopy. The SurveyMonkey portal (https://www.surveymonkey.com/) was used to administer the questionnaire. Of the 400 hysteroscopists who were approached, 229 replied. RESULTS: Routine pre-procedural or intra-procedural analgesia was used by 34% of hysteroscopists (67% of these reported using NSAIDs, 12% paracetamol, 7% opioids 13.5% other). Among hysteroscopists who routinely used intra-procedural analgesia, 46.1% reported using a paracervical block, 15.4% used an intracervical blockage, 15.4% had the patient listen to music during the procedure, 3.8% used local anesthetics, as in a spray or gel on the surface of the cervix, and 19.2% used some other method. Regarding misoprostol use, 75% of hysteroscopists reported not using it routinely. CONCLUSION: Our results are consistent with poor evidence from published studies that there is a low prevalence of routine analgesia use during outpatient hysteroscopy.

Synovial sarcoma of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 10 cases.

Only a few synovial sarcomas arising in the gastrointestinal tract have been reported, most of them are from the esophagus. We report clinical, histopathologic, and immunohistochemical features of 10 gastric synovial sarcomas. These tumors occurred in 4 males and 6 females with mean and median age of 52 years (range, 29 to 68 y). None of the patients had evidence of synovial sarcoma elsewhere. The tumor sizes ranged from 0.8 to 15 cm (mean, 3 cm). Two tumors were large transmural masses of 8 and 15 cm, and 8 were 0.8 to 6 cm, ulcerated cuplike or plaquelike or oval lesions predominantly involving the luminal side. Histologically, 9 tumors were monophasic one also having a poorly differentiated round cell component, and one was biphasic. Microscopic calcifications were present in 2 tumors. At least focal keratin (AE1/AE3 cocktail, keratin 7) and/or epithelial membrane antigen-positivity were detected in all tumors, and there was no CD34 or KIT-immunoreactivity. SYT-SSX fusion transcripts were demonstrated in 7 cases studied by a polymerase chain reaction-based fusion transcript assay. Five patients had a partial gastrectomy, and 5 underwent wedge or segmental resections. Two patients had received chemotherapy after surgery, but none had postoperative radiation. Four patients with plaquelike or cuplike tumors < or =3 cm were alive and well 1, 2, 2, and 18.5 years after surgery. Two patients died of tumor 25 and 29 months after surgery. One of them had a large 8-cm tumor, and another had a 2-cm tumor with a poorly differentiated component. Two patients were alive with recurrences 6 and 48 months after diagnosis. Synovial sarcoma rarely occurs as a gastric primary tumor. It has a variable prognosis depending on tumor size and differentiation, and should be considered in the differential diagnosis of KIT-negative gastric spindle cell neoplasms.

Familial thyroid carcinoma: a diagnostic algorithm.

Thyroid carcinomas derived from follicular cells are the most common endocrine malignancies, and papillary thyroid carcinoma (PTC) is the most common type. Although, the majority of papillary and follicular thyroid carcinomas (FTCs) are sporadic, familial forms have been described in recent years. Familial syndromes are classified into familial medullary thyroid carcinoma and familial nonmedullary thyroid carcinoma. Multifocal papillary carcinoma is the most frequent presentation of familial nonmedullary thyroid carcinoma, and based on clinico-pathologic findings it is divided into 2 groups. The first includes familial syndromes characterized by a predominance of nonthyroidal tumors, such as familial adenomatous polyposis, PTEN-hamartoma tumor syndrome, Carney complex type 1, and Werner syndrome. The second group includes familial syndromes characterized by a predominance of NMTC, such as pure familial (f) PTC with or without oxyphilia, fPTC with papillary renal cell carcinoma, and fPTC with multinodular goiter. Medullary thyroid carcinoma is derived from calcitonin-producing C cells. The familial form accounts for 20% to 25% of cases, and is usually a component of multiple endocrine neoplasia (MEN) IIA or IIB, or presents as pure familial medullary thyroid carcinoma syndrome. C-cell hyperplasia is the precursor lesion of these heritable syndromes. Some characteristic morphologic findings should alert the pathologist of a possible familial cancer syndrome, which may lead to further molecular genetic evaluation.

Lack of genetic association between exaggerated placental site reaction and placental site trophoblastic tumor.

Exaggerated placental site (EPS) reaction is a reactive or an exuberant physiologic process involving intermediate trophoblasts infiltrating the underlying endomyometrium at the implantation site. Sharing similar cytological and immunohistochemical features with the tumor cells of placental site trophoblastic tumor, a biological link between the 2 lesions can be speculated. Because placental site trophoblastic tumor has a unique sex chromosomal requirement in its genome that requires a paternal X chromosome (i.e. a female antecedent gestation), we investigated whether EPS carries the similar genetic profile by DNA genotypic analysis. Twenty cases of EPS were reviewed and analyzed by AmpFlSTR Identifiler polymerase chain reaction amplification system (Applied Biosystems, Inc., Foster City, CA). The genetic profile of all cases demonstrated unique paternal alleles to that of the paired maternal tissue, confirming the trophoblastic origin of EPS. The presence of an XY genome (male) was identified in 11 cases (55%), and an XX genome (female) was seen in the rest of 9 cases (45%). Therefore, EPS is a trophoblastic lesion that can arise from either male or female gestations. The assignment of sex chromosomes in our study (XY, 55% and XX, 45%) does not support a neoplastic association between placental site trophoblastic tumor and EPS.

Frequency of clinically occult intraepithelial and invasive neoplasia in reduction mammoplasty specimens: a study of 516 cases.

Reduction mammoplasty is a frequently performed procedure for the treatment of macromastia and for the achievement of symmetry in breast cancer patients following lumpectomy. Slides from 516 consecutive bilateral reduction mammoplasties performed for macromastia over 15 years were reviewed. Among these, 92 (18%) low-risk ductal intraepithelial neoplasia/intraductal hyperplasia, 28 (5%) ductal intraepithelial neoplasia 1 (1 low-grade ductal carcinoma in situ, 11 atypical intraductal hyperplasia, and 16 flat type), 17 (3%) lobular intraepithelial neoplasia, and 1 (0.2%) tubular carcinoma were identified. The patients were categorized into 3 age groups: <40 (n=352), 40 to 50 (n=107), and over 50 years (n=57); the frequency of the lesions increased with age. These data confirm the low frequency of clinically occult malignancies identified in reduction mammoplasty specimens and provide substantial information about the frequency of a variety of intraepithelial proliferations. Preoperative mammography, specimen orientation, and inking of margins with 1 color are advised when reduction mammoplasty is scheduled for women>or=40 years of age.

Expression of p63 in thymomas and normal thymus.

The p63 gene, a member of the p53 family, is an epithelial marker expressed in embryonic ectoderm, breast myoepithelium, prostate, oral epithelium, epidermis, and urothelium. The DeltaN-p63 isoforms of p63, which are believed to behave as oncogenes, are expressed in squamous cell carcinoma, basal cell carcinoma, and transitional cell carcinoma. Only a few authors have looked for p63 expression in thymomas and normal thymus. We, therefore, thought of undergoing such a search by taking advantage of our archival material. We studied 66 cases of thymoma (1 type A, 8 type AB, 12 type B1, 19 type B2, 12 type B3, and 14 type C/thymic carcinoma) and 10 specimens of normal human thymus arranged in tissue microarrays. All thymomas (including thymic carcinomas) were positive for p63 regardless of type. Most of the epithelial cells of the normal thymus were also positive for this marker.

Flat DIN 1 (flat epithelial atypia) on core needle biopsy: 63 cases identified retrospectively among 1,751 core biopsies performed over an 8-year period (1992-1999).

Uniform management of flat DIN 1 (flat epithelial atypia) on core needle biopsy (CNB) concerning surgical excision or clinical follow-up are lacking. In a retrospective review of 1,751 CNB over an 8-year period, we found 63 cases with flat DIN 1 as the most advanced lesion; follow-up was available in 55 cases. Of the 63 patients, 24 had a subsequent biopsy for 15 days to 10 years after the initial CNB, an infiltrating carcinoma was found in nine (14.3%) patients, seven (11.1%) in the ipsilateral, and two (3.2%) in the contralateral breast. Five underwent an excisional biopsy of the ipsilateral breast within less than 3 months of the initial CNB; none had either an invasive or intraepithelial carcinoma. Based on our findings, we consider flat DIN 1 a marker of slightly increased risk for subsequent development of invasive breast carcinoma. When flat DIN 1 is found on CNB as the most advanced lesion after mammographic correlation, an excisional biopsy is not mandatory; however, close follow-up is advised with repeat mammograms for early detection of any clinically occult carcinoma in the vicinity of flat DIN 1 that may have been missed by the CNB.

Primary malignant melanoma of the transverse colon: report of a case and review of the literature.

Gastrointestinal involvement by malignant melanoma is predominantly a metastatic phenomenon. Although primary malignant melanoma of the gastrointestinal tract has been documented in the esophagus, stomach, small bowel, and anorectum, the incidence of primary melanoma of the colon is rare and remains controversial in most cases. We present a case of solitary malignant melanoma of the transverse colon occurring in a 64-year-old African American male patient. Complete dermatologic and ophthalmologic examinations revealed no evidence of a cutaneous or an ocular primary lesion. Microscopic examination of the resection specimen revealed malignant melanoma, which was confirmed by immunohistochemical positivity for S100 and melan-A. We believe that this tumor represents a primary colonic malignant melanoma.

Hypercalcemia of malignancy due to ectopic transactivation of the parathyroid hormone gene.

CONTEXT: The physiology of PTH is well described, but regulation of PTH gene expression remains enigmatic. This is, at least in part, because of a lack of suitable cell culture systems. OBJECTIVE, DESIGN, SETTING, PATIENTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: We report a case of severe hyperparathyroidism resulting from the ectopic production of PTH by a pancreatic malignancy. Cells from the primary tumor (PEPP1 cells) were established in culture to examine the etiology of ectopic PTH gene expression in this patient. RESULTS AND CONCLUSIONS: We failed to find amplification or rearrangement of the PTH gene but documented hypomethylation of the PTH promoter in tumor tissue. We found that PEPP1 cells support expression of a reporter gene containing regulatory sequences from the human PTH gene promoter. Therefore, this is the first report documenting ectopic PTH production by a tumor as the result of transactivation of the PTH gene. PEPP1 cells may be useful for future studies aimed at elucidating the details of PTH gene regulation.

High grade cervical intraepithelial neoplasia and viral load of high-risk human papillomavirus: significant correlations in patients of 22 years old or younger.

High-risk human papillomavirus (HR-HPV) is recognized as the primary cause for the development of cervical cancers and their precursor lesions. We investigated whether high-grade cervical dysplasia correlates with high viral load of HR-HPV in an age-dependent manner. Cases were retrospectively selected to include patients with a prior cytological diagnosis of ASCUS or higher grade squamous intraepithelial lesions, and a positive Digene Hybrid Capture II (HC-II) HR-HPV testing within 2 months before or after cervical biopsy. The quantitative viral load data was classified as negative, low, moderate and high according to the manufacturer's instruction. Cases were then stratified into 4 age groups: 40 years. Chi-Square analysis and logistic regression were performed where appropriate. A total of 995 patients were identified. Age categories were significantly associated with HPV loads (p=0.046). Moderate to high viral loads of HPV were significantly related to the histological grade of dysplasia (p=0.029). Logistic regression analysis further confirmed the association of HPV with histological grades, even after adjusting for age factor. In particular, high-grade dysplasia (p=0.011) but not low grade dysplasia (p=0.140) was significantly associated with moderate to high HPV loads. Patients of 22 years old or younger were the only group found significantly correlated with high viral loads of HPV (p=0.015). In conclusion, high-grade squamous intraepithelial lesions and patients' age of 22 years old or younger are significantly associated with a moderate to high viral load of HR-HPV.

Primary or secondary? Genotyping confirmation of an ovarian primary carcinoid tumor.

Ovarian primary carcinoid tumors of pure histological type can pose a significant diagnostic challenge in its separation from metastatic carcinoids from the gastrointestinal tract. Yet, their clinical management and prognosis are drastically different. At the molecular level, ovarian primary carcinoid tumors are thought to be of germ cell origin, frequently after the first meiotic division. We report a 21.5-cm ovarian insular carcinoid tumor in a 50-year-old woman who had no evidence of extraovarian tumor. The absence of teratomatous components and the presence of lymphovascular invasion prompted additional studies to rule out a metastatic tumor. The nature of this primary ovarian tumor was eventually confirmed by demonstration of its germ cell origin through DNA genotyping.

p63 is a useful marker for cutaneous spindle cell squamous cell carcinoma.

BACKGROUND: Cutaneous spindle cell squamous cell carcinoma (SCSCC) is a rare variant of SCC. This lesion is sometimes difficult to diagnose based purely on morphologic features. p63 is a member of the p53 gene family that can be identified in epithelial malignancies. METHODS: Thirteen cases of spindle SCC were stained with p63, CK34betaE12, MNF116, vimentin, and S100. Control cases included desmoplastic melanoma (eight cases), atypical fibroxanthoma (AFX) (10 cases), dermatofibrosarcoma protuberans (eight cases), and cutaneous leiomyosarcoma (LMS) (four cases). RESULTS: p63 was expressed diffusely in the nuclei of 100% (13/13) of SCSCCs. Of controls, p63 showed focal labeling of two LMS and two AFX. MNF116 and CK34betaE12 were positive in 13/13 SCSCCs. Of controls, one LMS was focally positive for MNF116. All SCSCCs and all control cases were positive for vimentin. CONCLUSIONS: In the given differential diagnosis, p63 appears relatively specific to SCSCC and adds a useful nuclear marker to the available repertoire. The findings also suggest that cytokeratins MNF116 and CK34betaE12 may be more useful than standard cytokeratins in labeling SCSCC.

Solitary fibrous tumor of the larynx: a case report and review of the literature.

Solitary fibrous tumors are relatively rare mesenchymal neoplasms that were originally described as pleural- or peritoneal-based lesions. Although they were considered a form of mesothelioma, subsequent investigation failed to reveal mesothelial differentiation. Characterization of their histologic and immunohistochemical features, as well as identification in a multitude of nonmesothelial-based locations has further served to distinguish these lesions from the more diffuse and aggressive mesothelioma. Reports of solitary fibrous tumor in the larynx are extremely rare. We report a case of solitary fibrous tumor of the larynx in a 38-year-old man.

Squamous cell carcinoma of the pancreas.

Squamous cell carcinoma of the pancreas is a rare condition. The incidence has been estimated at approximately 1% of all pancreatic malignancies. The histogenesis is uncertain, but it has been proposed to originate from areas of squamous metaplasia of pancreatic ductal epithelium. We present a case of a 56-year-old man who presented with back pain and was found to have a squamous cell carcinoma of the pancreas without evidence of metastatic disease. Three months after en bloc resection with negative margins and lymph nodes, he presented with widely metastatic disease. A review of the literature on the topic is presented, and the poor prognosis of this rare tumor, despite complete surgical resection, is discussed.

Classification of microhysteroscopic images and their correlation with histologic diagnoses.

STUDY OBJECTIVE: To confirm that images observed at hysteroscopy correlate with histopathologic diagnoses. DESIGN: Double-blind study (Canadian Task Force classification II-2). SETTING: Gynecologic cancer center, private institute. SUBJECTS: One thousand four hundred thirty-six uterine cavities. INTERVENTION: Hysteroscopy. MEASUREMENTS AND MAIN RESULTS: Images were classified as normal hysteroscopy, benign lesion, low-risk hyperplasia, high-risk hyperplasia, and carcinoma. A hysteroscopic diagnosis was made and biopsy specimens were obtained with Kevorkian-type curettes or Sims curettes. Tissues were studied by a pathologist, after which we compared endoscopic diagnoses with anatopathologic diagnoses. Significant correlation was found between suspicion based on images and histologic confirmation (p = 0.001). The Cramer V coefficient, which measures the relationship between both methods, was high: 0.925. The Cramer V coefficient takes values ranging from zero, to indicate lack of correlation, to 1, to indicate perfect correlation. A lambda symmetry coefficient of 0.96 is interpreted as probable improvement in the prediction of histologic diagnosis based on images. CONCLUSION: This classification system can be useful for a systematic approach to hysteroscopic findings and to improve communication among specialists. It is based on the degree of hysteroscopic suspicion aimed at early detection of endometrial cancer and its precursor lesions.