Charles V. Biscotti

Gorham's syndrome: A case report and review of the literature

Gorhams syndrome is a rare disorder involving a proliferation of vascular channels associated with extensive loss of bony matrix. A case report is presented with a review of the 97 previously reported cases. The age of patients at presentation has ranged from less than one to 75 years (mean: 27 years). Sixty-four percent have been men. Fifty-seven percent have had a history of prior trauma. Laboratory values for systemic measures have usually been normal. The disease usually arrests spontaneously, but this is unpredictable. Sixteen patients (16 percent) have died of the disorder, with 10 deaths due to chest wall involvement, three to spinal cord transection, two to sepsis, and one to asphyxia and aspiration. Although the mechanism of bone loss is unknown, osteoclasts were focally increased in the case described herein. Further information and investigation are needed to better understand this unusual disorder.

Restoration of ovarian function after autotransplantation of intact frozen-thawed sheep ovaries with microvascular anastomosis

OBJECTIVE To test the feasibility of transplanting an intact frozen-thawed ovary with microvascular anastomosis of the ovarian vascular pedicle to the deep inferior epigastric vessels. DESIGN Chronic survival study. SETTING Biological Resources Unit, The Cleveland Clinic Foundation. ANIMAL(S) Adult merino ewes. INTERVENTION(S) Bilateral laparoscopic oophorectomy was performed on 17 synchronized ewes. In one group of animals (Group I, n = 11), both ovaries were cryopreserved intact with their vascular pedicles. In another group of animals (Group II, n = 6), ovarian cortical strips were prepared from each ovary and cryopreserved. After thawing, follicular viability and apoptosis rates were assessed using one ovary. The other ovary was transplanted to the abdominal wall with microvascular anastomosis (Group I). In Group II, the ovarian cortical strips were placed in the anterior abdominal wall. Ovaries were harvested after 8-10 days in situ and subjected to histological evaluation. MAIN OUTCOME MEASURE(S) Blood flow, apoptotic signals, follicular viability, serum estradiol (E(2)), follicle-stimulating hormone (FSH), and histology. RESULT(S) No significant differences were found in the mean values of apoptosis (mostly in the atretic and some secondary follicles) and follicular viability in both groups. In Group I, immediate and long-term patency were documented in 100% and 27% (3/11) of the grafts, respectively; and postoperative FSH levels were similar to preoperative values in animals with patent vessels. In Group II, postoperative FSH levels were significantly higher than the preoperative ones (P=.03). CONCLUSION(S) Transplantation of an intact frozen-thawed ovary is technically feasible. Using this approach, immediate restoration of vascular supply and ovarian hormonal functions is possible.

Heterotopic autotransplantation of the ovary with microvascular anastomosis: A novel surgical technique

OBJECTIVE To test the feasibility of transplanting an entire ovary with anastomosis of the ovarian vascular pedicle. DESIGN Long-term survival study. SETTING Biological Resources Unit, Cleveland Clinic Foundation. ANIMAL(S) Five adult, nonpregnant ewes. INTERVENTION(S) Laparoscopic bilateral oophorectomy was performed. Ovaries were autotransplanted into the abdominal wall, and microsurgical vascular anastomosis of the ovarian to the inferior epigastric vessels was performed. The transplant was removed and evaluated after 7 +/- 1 days. MAIN OUTCOME MEASURE(S) Blood flow, serum E2 and FSH levels, and histologic characteristics. RESULT(S) At follow-up three transplants were viable; they showed no signs of necrosis, and patency of the vascular anastomosis was confirmed. Serum E2 levels did not change significantly after transplantation in the patent vessel group (155.3 +/- 46.1 vs. 125.7 +/- 44.6 pg/mL) or the nonpatent vessel group (99 vs. 158 pg/mL). Serum FSH level in the patent vessel group did not change significantly from before to after transplantation (70.6 +/- 37.2 ng/mL vs. 95.1 +/- 17.7 ng/mL), whereas a large increase in FSH level was observed in the nonpatent vessel group (52.3 ng/mL vs. 522 ng/mL). The patent vessel group had significantly more follicles after transplantation than did the nonpatent vessel group (6 +/- 1 vs. 1 +/- 1). CONCLUSION(S) In conjunction with improved protocols for cryopreservation, ovarian autotransplantation with vascular anastomosis may be superior to current ovarian tissue banking and grafting techniques.

Peritoneal serous micropapillomatosis of low malignant potential (serous borderline tumors of the peritoneum). A clinicopathologic study of 17 cases.

Primary peritoneal serous micropapillomatosis of low malignant potential, or serous borderline tumor of the peritoneum, is a relatively rare lesion that is histologically indistinguishable from peritoneal “implants” associated with ovarian papillary serous tumors of low malignant potential. We analyzed 17 cases to further define the pathologic features and prognosis of this entity. The ages of the patients ranged from 16 to 67 years (mean, 33 years). Eight patients were symptomatic with chronic pelvic or abdominal pain (five patients), adnexal mass (one patient), small-bowel obstruction (one patient), and possible endometriosis (one patient). In nine cases (53%), peritoneal serous micropapillomatosis of low malignant potential was an incidental finding discovered during evaluation or treatment of other conditions. Grossly, the peritoneal lesions were focal or diffuse. They commonly appeared as miliary granules and often were believed to be peritoneal carcinomatosis. Microscopically, peritoneal serous micropapillomatosis of low malignant potential had all of the patterns seen in superficial (“noninvasive”) peritoneal implants of ovarian serous borderline tumors. Psammoma bodies were a prominent feature of all cases. Twelve patients also had typical endosalpingiosis. Most patients were treated by hysterectomy and bilateral salpingo-oophorectomy. Surgical treatment in seven patients consisted only of biopsy. Ten patients had residual unresected disease at the time of their initial operation. Several patients received adjuvant chemotherapy. Follow-up was available for 14 of the 17 patients. One patient died of metastatic breast carcinoma at 3.8 years; another patient died 7 weeks after operation, possibly as a complication of therapy. The other 12 patients were alive at last known contact after follow-up intervals of 8 months to 16.2 years (mean, 7.5 years). Two of these 12 patients developed multiple episodes of small-bowel obstruction due to persistent peritoneal serous micropapillomatosis of low malignant potential; neither received adjuvant chemo- or radiotherapy. Both were alive without progressive disease 10.9 and 16.2 years after initial diagnosis, respectively. This excellent prognosis supports a regimen of conservative therapy for these patients.

Implementation of tumor testing for lynch syndrome in endometrial cancers at a large academic medical center

OBJECTIVES Lynch syndrome (LS) is a hereditary condition that increases the risk for endometrial and other cancers. Recognizing women at risk for LS based on personal/family history is burdensome and imprecise. Tumor testing using microsatellite instability (MSI) testing and immunohistochemistry (IHC) for mismatch repair protein expression can be an effective strategy for identifying potential LS in patients presenting with colorectal or endometrial cancer. Here we describe our experience implementing a screening program for endometrial cancers. METHODS Endometrial cancers diagnosed ≤50 years or those with suspicious personal history or histopathologic features were screened with MSI/IHC, June 2009-June 2011. Criteria were later (July 2011-July 2012) expanded to patients diagnosed <60 years, or at any age with suspicious features, and finally (after August 2012) universal screening was implemented. Screening techniques began with both MSI and IHC for every tumor, and later converted to IHC for two proteins, and MLH1 promoter methylation analysis when indicated. A genetic counselor contacted patients directly to offer genetic counseling appointments. RESULTS Two hundred and forty-five endometrial cancers (average age, 57 years) were screened. Sixty-two patients (25%) had abnormal results, and 42 patients were referred for genetic counseling. Of the 42 patients, 34 underwent genetic counseling, 28 pursued genetic testing, and 11 were diagnosed with LS. When age and pathology criteria were used, 27 eligible cases were overlooked for screening and 3 cases of LS were found only because a clinician requested screening. CONCLUSIONS Universal screening of endometrial cancers for LS is practical and successfully implemented with collaboration among genetic counselors, gynecologic oncologists, and pathologists.

Histopathologic findings in 107 uterine leiomyomas treated with leuprolide acetate compared with 126 controls.

The reported histopathologic findings in leiomyomas treated with leuprolide acetate (LA) differ. We examined 233 myomectomy specimens, including 107 myomas from 30 patients (mean age, 34.7 +/- 4.6 years) treated with LA. Their histopathologic findings were compared with those from a control group of 126 myomas from 30 untreated patients (mean age 32.7 +/- 5.3 years). The LA-treated leiomyomas had myxoid change (n = 2; 1.9%), total necrosis (n=4; 3.7%), focal necrosis (n = 5; 4.7%), calcifications (n = 5; 4.7%), hemorrhage (n = 8, 7.5%), vascular changes (n = 12; 11.2%), hydropic degeneration (n = 22; 20.5%), and hyalinization (n = 61; 57.0%). None of these changes differed significantly from the untreated controls. None of the LA-treated leiomyomas had nuclear atypia, whereas nuclear atypia occurred in four (3.2%) of the untreated leiomyomas; this difference was also not significant. Mitotic figures were present in 8.4% of the LA-treated myomas and 8.5% of untreated controls. The number of mitotic figures per 10 high-power fields was slightly higher in the untreated myomas, but the difference was not statistically significant (range, 0-3 for treated, 0-5 for controls). The degree of cellularity did not differ between the two groups. In conclusion, (a) LA-treated myomas do not significantly differ from untreated myomas with respect to nuclear atypia, calcification, total coagulative necrosis, focal coagulative necrosis, hemorrhage, vascular changes, myxoid change, hydropic degeneration, hyalinization, mitotic activity, or cellularity; and (b) the mechanism leading to a reduction in the size of myomas treated with LA is not apparent from routine histologic examination.

Apoptotic bodies: a consistent morphologic feature of endocervical adenocarcinoma in situ.

To evaluate the occurrence of apoptotic bodies in endocervical adenocarcinoma in situ (AIS) and investigate the relationship of apoptosis to mitotic activity, we performed counts of apoptotic bodies and mitotic figures in 43 patients with AIS and in a comparable control group with nonneoplastic endocervical glandular epithelium. The ages of the patients with AIS ranged from 27 to 74 years (mean = 40). Mitotic figures were present in all AIS cases, and apoptotic bodies were seen in all but two extremely small lesions. In 28 AIS cases in which lesions were large enough to count 10 consecutive high-power fields (HPF), counts of apoptotic bodies ranged from 1 to 36/10 HPF (mean and median = 16), and counts of mitotic figures ranged from 1 to 53 mitotic figures/10 HPF (mean and median = 18). Counts of apoptotic bodies correlated directly with counts of mitotic figures. The ages of the 28 control patients ranged from 32 to 56 years (mean = 43). Counts of apoptotic bodies in the control cases ranged from 0 to 10 per case (mean = 1.1). Apoptotic bodies were present in only 13 (46%) control cases. The highest counts in these cases ranged from 1 to 6 apoptotic bodies/10 HPF (mean = 2.3). Mitotic figures were present in only 4 (14%) control cases. The counts in these cases ranged from 1 to 3 mitotic figures/10 HPF (mean = 1.8). Counts per 10 HPF were significantly (p < 0.001) more for AIS cases than for controls for apoptotic bodies and mitotic figures. Our results indicate that apoptotic bodies, as well as mitotic figures, occur almost universally in AIS. Both occur significantly more often and in greater numbers in AIS than in nonneoplastic endocervical glandular epithelium. Apoptotic bodies are a consistent morphologic feature of AIS, and their identification may be diagnostically useful.

Assessment of tissue injury in cryopreserved ovarian tissue

Ovarian tissue banking is a developing technique aimed to preserve fertility in women at risk for premature ovarian failure (1–3). It entails cryopreservation of ovarian tissue with the option of autografting. Reports on the autografting of cryopreserved ovarian cortex segments describe the resumption of steroid production (4), follicle development (5, 6), and (in sheep) model successful pregnancies (7, 8). However, tissue loss due to procedural steps is expected to have detrimental effects on the reproductive potential of frozen-thawed ovarian grafts. We conducted a study in a porcine model to investigate how freezing and thawing affects ovarian tissue and whether warm ischemia time before the cryopreservation process has any added detrimental effects.

Pancreatic cyst aspiration analysis for cystic neoplasms: Mucin or carcinoembryonic antigen—Which is better?

BACKGROUND Differentiation between the various pathologies presenting as a cystic pancreatic lesion is clinically important but often challenging. We have previously advocated the performance of endoscopic ultrasound (EUS) with aspiration and determination of mucin and carcinoembryonic antigen (CEA) content. We sought to report the results of this ongoing protocol and determine the relative importance of cyst fluid mucin and CEA for the diagnostic process. METHODS The institutions prospectively maintained pancreatic cyst database was accessed to identify patients who had undergone pancreatic EUS and cyst aspiration as part of their evaluation. Only those patients who had subsequently undergone resection were selected, with histopathology being the gold standard for comparison. RESULTS From January 2000 to July 2009, 174 patients with pancreatic cystic disease underwent surgery, 121 of whom had an EUS with aspiration attempted at our institution with specimens sent for mucin and CEA. Based on histopathology, 86 mucinous lesions were identified, including 44 cystadenomas, 34 intraductal papillary mucinous neoplasms, 7 mucinous adenocarcinomas, and 1 intraductal oncocytic papillary neoplasm; 42 were nonmucinous lesions. The median cyst CEA levels were significantly higher in the mucinous lesions group at 850 versus 2 ng/mL (P = .001). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive diagnostic likelihood ratio, and negative diagnostic likelihood ratio (NDLR) were calculated respectively for mucin alone (0.80, 0.40, 0.61, 0.63, 1.33, 0.68); CEA alone (0.93, 0.43, 0.51, 0.91, 1.63, 0.16); cytology alone (0.38, 0.9, 0.92, 0.31, 3.67, 0.69); mucin or CEA (0.83, 0.65, 0.87, 0.57, 2.51, 0.26); mucin or CEA or cytology (0.92, 0.52, 0.86, 0.68, 1.91, 0.15); mucin plus CEA (0.96, 0.34, 0.25, 0.97, 1.45, 0.12); mucin plus cytology (0.25, 0.97, 0.96, 0.29,7.25, 0.78); CEA plus cytology (0.12, 1.00, 1.00, 0.26, ∞, 0.88); and mucin plus CEA plus cytology (0.08, 1.00, 1.00, 0.25, ∞, 0.92). CONCLUSION Assessment of cyst mucin and CEA are complementary, with the best profile obtained when both markers are determined along with cytology. This combination provides a good sensitivity, PPV, and NDLR, as well as reasonable PPV and PDNR.

Primary screening with liquid-based cytology in an unscreened population in rural China, with an emphasis on reprocessing unsatisfactory samples

OBJECTIVE To determine the sensitivity and specificity of liquid-based cytology in a high-risk, unscreened population. STUDY DESIGN A cross-sectional comparative trial of multiple screening techniques. This report focuses on the performance of liquid-based cytology using biopsy as the standard. RESULTS In total, 1,997 women were screened. All subjects had a minimum of five cervical biopsies. Of the subjects, 4.3% had CIN 2 on biopsy. The ThinPrep Pap with ASCUS as positive had a sensitivity for CIN 2 of 94% and specificity of 78%; the sensitivity for CIN 3 was 98% and for cancer, 100%. The unsatisfactory rate due to bloody specimens was 7.9% (158/1,997). After reprocessing, the unsatisfactory rate was 0.15% (3/1,997). CONCLUSION Reprocessing effectively recovers ThinPrep samples otherwise unsatisfactory due to blood and mucus. The ThinPrep Pap test is a highly sensitive screening test when used in a high-risk, unscreened population.