Kelley S. Carrick

In situ and invasive adenocarcinomas of the gallbladder extending into or arising from Rokitansky-Aschoff sinuses: a clinicopathologic study of 49 cases.

We report 49 cases of gallbladder carcinomas that extended into or originated from Rokitansky-Aschoff sinuses (RAS), all of which were resected by laparoscopic cholecystectomy. Twenty-one tumors were in situ carcinomas that extended along RAS; six in situ carcinomas arose in adenomyomatous hyperplasia and 22 were invasive adenocarcinomas with extension into RAS. Thirty-seven patients were women and 12 men. Forty patients had cholelithiasis. The age of the patients ranged from 55 to 84 years (mean 67 years). All in situ carcinomas were incidental microscopic findings in gallbladders removed for cholelithiasis and/or cholecystitis. No patient with in situ carcinoma died as a result of the tumor, including two with in situ carcinoma that originated in adenomyomatous hyperplasia and showed microinvasion. In contrast, of 15 patients with invasive well to moderately differentiated adenocarcinoma extending into RAS and invading the muscle layer or subserosal connective tissue, 8 died 2 to 4 years after surgery. Seven patients survived 1 to 8 years after cholecystectomy. Useful clues to separate RAS with in situ carcinoma from tubular neoplastic invasive glands were the following: connection of the epithelial invaginations to the surface epithelium, recognition of normal biliary epithelium admixed with neoplastic epithelium, presence of inspissated bile in long dilated spaces, and lack of invasion to the smooth muscle bundles. In situ carcinoma spreading along RAS consisted of long tubular often dilated structures extending through the intermuscular connective tissue, whereas neoplastic glands were usually small or of medium size that invaded smooth muscle bundles or intermuscular connective tissue. Perineural invasion was seen only in invasive glands located in the subserosal connective tissue. Two cases of in situ carcinoma that arose in adenomyomatous hyperplasia and three invasive adenocarcinomas that were composed predominantly of tall columnar mucin containing cells similar to gastric foveolar cells with varying degrees of atypia and cells with biliary phenotype bear some resemblance to intraductal papillary mucinous carcinoma of the pancreas or to mucinous cystic pancreatic neoplasm. Metaplastic pyloric glands often seen in the muscle layer and subserosal connective tissue maintain their lobular pattern and should not be confused with invasive glands. Our findings indicate that distinction of in situ carcinoma spreading into RAS from tubular neoplastic glands of invasive adenocarcinomas is crucial to determine prognosis in this group of patients with gallbladder carcinoma.

Comparison of ThinPrep and Conventional Smears in Detecting Carcinoma in Bile Duct Brushings

Bile duct brushing cytology is a common procedure for the exclusion of adenocarcinoma in the bile duct. The authors evaluated the use of ThinPrep® (TP) to determine whether the information obtained is equivalent to that found with conventional smear cytology (CS).

CD56 reactivity in small cell carcinoma of the uterine cervix

Small cell carcinoma (SCC) of the uterine cervix, like its pulmonary counterpart, is a rare but distinctive neoplasm that should be separated from nonendocrine carcinomas because of its highly aggressive clinical course and response to chemotherapy and irradiation. CD56 (neural cell adhesion molecule) has recently been shown to be the best marker for the diagnosis of pulmonary SCC. In this study, we assessed the sensitivity and specificity of CD56 in the diagnosis of SCC of the uterine cervix compared with those of chromogranin and synaptophysin. Twenty-two (88%) of 25 SCCs of the uterine cervix labeled with CD56 in a predominantly membranous and diffuse pattern, whereas 16 of 25 (64%) stained with synaptophysin in a predominantly diffuse pattern and 8 of 25 (32%) showed predominantly focal immunoreactivity for chromogranin. In contrast, 3 of 21 (14%) moderately to poorly differentiated squamous cell carcinomas and 1 of 16 (6%) moderately differentiated adenocarcinomas showed focal immunoreactivity for CD56. Although not specific, CD56 seems to be the most sensitive marker for the diagnosis of SCC of the uterine cervix. Moreover, its diffuse reactivity reduces the possibility of obtaining negative results in small biopsy samples.

Papillary carcinomas of the gallbladder: analysis of noninvasive and invasive types.

CONTEXT Although papillary carcinomas have been recognized as distinct morphologic variants of gallbladder neoplasms, they have been lumped together in a single group despite the recognition of noninvasive and invasive types. As a result, the biologic behavior of each type remains undescribed. OBJECTIVE To compare the biologic behavior of noninvasive and invasive papillary carcinomas of the gallbladder. DESIGN The clinical and morphologic features of 16 noninvasive papillary carcinomas (>1 cm) of the gallbladder were analyzed, and their clinical behavior was compared with that of 370 invasive papillary carcinomas recorded in the Survey Epidemiology and End Results (SEER) Program of the National Cancer Institute from 1973 through 2001. The biologic behavior of invasive papillary carcinomas was compared with that of invasive nonpapillary carcinomas of the gallbladder recorded in SEER. Hematoxylin-eosin-stained sections were available for review in the 16 noninvasive papillary carcinomas. The number of slides examined per case varied from 3 to 16, with an average of 7. RESULTS The 16 patients with noninvasive papillary carcinomas included 11 women and 5 men, aged 34 to 83 years (mean age, 61 years). Thirteen patients had cholelithiasis. Laparoscopic cholecystectomy was performed on 12 patients and open cholecystectomy on 4. The tumors measured from 1.3 to 8.6 cm and were well to moderately differentiated. Fourteen noninvasive papillary carcinomas showed biliary phenotype, and 2 showed intestinal phenotype. Follow-up was obtained in 11 patients; 6 were asymptomatic 5 to 11 years after surgery, 2 were symptom free 9 months to 4 years following cholecystectomy, and 3 died of unrelated causes 2 to 3 years after surgery. Three hundred seventy cases of invasive papillary carcinomas were recorded in SEER. The 10-year relative survival rate for 225 patients with invasive papillary carcinomas confined to the gallbladder wall was 52%, while the 10-year relative survival rate for 83 patients with papillary carcinomas that had spread to the lymph nodes was less than 10%. Of the remaining 62 invasive papillary carcinomas, 58 had distant metastases and 4 were not staged. The 10-year relative survival rate for invasive nonpapillary carcinomas confined to the gallbladder wall was 30%. CONCLUSION Noninvasive papillary carcinomas of the gallbladder-regardless of size, cell phenotype, and degree of differentiation-do not metastasize, and a simple cholecystectomy appears to be a curative procedure. In contrast, invasive papillary carcinomas do metastasize and are associated with a poor prognosis (10-year relative survival rate for tumors confined to the gallbladder wall was 52%, while the 10-year relative survival rate for tumors with lymph node metastasis was <10%). The separation of papillary carcinomas into noninvasive and invasive types is clinically relevant and therefore fully justified.

Where to set the threshold between well differentiated and poorly differentiated follicular carcinomas of the thyroid

A critical review of the literature reveals that different types of thyroid carcinomas have been interpreted as poorly differentiated, including the tall and columnar cell variants as well as carcinomas with insular, trabecular, and solid growth patterns. In some publications the growth patterns have been emphasized, while in others histologic patterns and cytologic features are considered important for identification. However, insular, trabecular, nodular, and solid growth patterns lack specificity because they can be observed in hyperplastic lesions and benign thyroid tumors. The cytologic features of the vast majority of poorly differentiated thyroid carcinomas are similar to or overlap with those of papillary or follicular carcinomas. Cytologic atypia, mitotic activity, and necrosis—believed by some investigators to be useful clues in the diagnosis of poorly differentiated carcinomas—do not reflect cell differentiation, especially in endocrine organs. It is therefore not surprising that the immunohistochemical profile and the molecular abnormalities described in this heterogeneous group of carcinomas lack specificity and are not useful diagnostic tools. Because poorly differentiated thyroid carcinomas have not been well defined, currently it is not possible to set the threshold between well-differentiated and poorly differentiated thyroid carcinomas with follicular phenotype. The authors believe that the vast majority of poorly differentiated thyroid carcinomas are in fact examples of papillary or follicular carcinomas with unusual growth patterns.

Optimal location and orientation of suture placement in abdominal sacrocolpopexy.

OBJECTIVE: To estimate the strongest location and optimal orientation of suture placement in the anterior longitudinal ligament for abdominal sacrocolpopexy in female cadavers. METHODS: The anterior longitudinal ligament was exposed below the level of the aortic bifurcation in 23 unembalmed female cadavers. To the right of midline of the vertebral column, sutures were placed in a horizontal orientation into the ligament at the sacral promontory, 1 and 2 cm above (sacral promontory+1 and sacral promontory+2), and 1, 2, and 3 cm below (sacral promontory–1, sacral promontory–2 and sacral promontory–3). At these same locations, but to the left of midline, sutures were placed in a vertical orientation. Pull-out force and ligament thickness at each level of testing were measured. Data were analyzed using Student t test and repeated measures analysis of variance. RESULTS: Sutures (either horizontally or vertically placed) had greater pull-out strengths at or above, compared with those placed below, the level of the sacral promontory. At sacral promontory and sacral promontory+1, there were no differences in the pull-out strengths of the ligament when sutures were placed in either orientation. However, horizontally placed sutures had significantly greater pull-out strengths than vertically placed sutures at sacral promontory+2, sacral promontory–1 and sacral promontory–2. Ligament thickness decreased from 2 cm above (mean±standard error of the mean sacral promontory+2, 1.8±0.1 mm) to 3 cm below (sacral promontory–3, 1.3±0.1 mm) the sacral promontory. CONCLUSION: Sutures placed in the anterior longitudinal ligament at or above the sacral promontory are more secure than those placed below. Horizontally oriented sutures should be considered for mesh attachment below the sacral promontory because they are significantly stronger when compared with vertically placed sutures. LEVEL OF EVIDENCE: III

Clinical, Biochemical, and Molecular Characterization of Macronodular Adrenocortical Hyperplasia of the Zona Reticularis: A New Syndrome

CONTEXT Macronodular adrenocortical hyperplasia classically presents with progressive hypercortisolemia and Cushing syndrome. We describe a 29-yr-old man with massive macronodular adrenocortical hyperplasia without hypercortisolemia but rather markedly elevated and nonsuppressible production of dehydroepiandrosterone (DHEA) and its sulfate (DHEAS). OBJECTIVE To characterize the clinical and molecular features of this case and to determine whether the tissue biochemically resembles the zona reticularis or fetal adrenal. SETTING University clinic, hospital, and laboratories. DESIGN Static and dynamic blood and urine testing were performed preoperatively. Tissue was studied by light microscopy, immunoblot, RNA microarray, and enzyme assay. PARTICIPANT A 29-yr-old man with incidentally discovered bilateral adrenal enlargement. INTERVENTION Bilateral adrenalectomy. MAIN OUTCOME MEASURES Molecular studies compared with control samples. RESULTS Hypercortisolism and 21-hydroxylase deficiency were excluded. DHEA, DHEAS, and 17-hydroxypregnenolone were markedly elevated and did not suppress with dexamethasone 2 mg/d for 4 d. Homogenates of the adrenals demonstrated high 17-hydroxylase, good 17,20-lyase, and low or absent 21-hydroxylase and 3β-hydroxysteroid dehydrogenase activities. Immunoblots confirmed robust expression of cytochrome P450c17 and AKR1C3 but not P450c21. Microarray analysis demonstrated high CYP11A1 and CYP17A1 expression but low or absent HSD3B1, HSD3B2, and CYP21A2 expression. Expression of mRNA for cytochrome b(5) (CYB5A) and AKR1C3, markers of the zona reticularis, were markedly elevated. CONCLUSION This is the first case of macronodular hyperplasia of the adrenal zona reticularis confirmed with studies of enzyme activity, mRNA expression, and protein identification. We speculate that this condition can be clinically silent in men but might cause severe hyperandrogenemia in women.

Giant myxomas of the maxillofacial skeleton and skull base

OBJECTIVES: To review our experience with patients diagnosed with giant myxomas of the maxillofacial skeleton. STUDY DESIGN: All patients undergoing excision of myxomas of the head and neck from September 1998 through September 2003 with a minimum follow-up of 1 year by the senior author (YD) were included in the study. METHODS: A retrospective chart review was conducted to select all patients who met the inclusion criteria. Clinical presentation, preoperative radiology findings, excisions performed, reconstruction, and follow-up were recorded and reported. RESULTS: Four patients were identified who met the inclusion criteria. All underwent wide en bloc excision of the tumor with various reconstructions. Complete resection was achieved in each case, and no patients have had evidence of recurrence. CONCLUSIONS: Giant myxomas of the maxillofacial skeleton have been reported to have significant rates of recurrence. Wide en bloc resection with appropriate reconstruction can result in excellent quality of life postoperatively and minimize the risk of recurrence. Lesser resections may not be appropriate especially in giant myxomas because of the potential morbidity that would be associated with a multifocal recurrence.

Anatomic relationships of the pelvic autonomic nervous system in female cadavers: clinical applications to pelvic surgery

BACKGROUND: The integrity of the pelvic autonomic nervous system is essential for proper bowel, bladder, and sexual function. OBJECTIVE: The purpose of this study was to characterize the anatomic path of the pelvic autonomic system and to examine relationships to clinically useful landmarks. STUDY DESIGN: Detailed dissections were performed in 17 female cadavers. Relationships of the superior hypogastric plexus to aortic bifurcation and midpoint of sacral promontory were examined; the length and width of plexus was documented. Path and width of right and left hypogastric nerves were recorded. The origin and course of the pelvic splanchnic nerves were documented. Individual nerve tissue that contributed to the inferior hypogastric plexus was noted. Relative position of nerves to arteries, viscera, and ligaments was documented. In a subset of specimens, biopsy specimens were obtained to confirm gross findings by histologic analysis. Descriptive statistics were used for data analyses and reporting. RESULTS: In all specimens, the superior hypogastric plexus was embedded in a connective tissue sheet within the presacral space, just below the peritoneum. In 14 of 17 specimens (82.4%), the plexus formed a median distance of 21.3 mm (range, 9–40 mm) below aortic bifurcation; in the remaining specimens, it formed a median distance of 25.3 mm (range, 20.5–30 mm) above bifurcation. In 58.8% of specimens, the superior hypogastric plexus was positioned to the left of midline. The median length and width of the plexus was 39.5 (range, 11.5–68) mm and 9 (range, 2.5–15) mm, respectively. A right and left hypogastric nerve was identified in all specimens and formed a median distance of 23 mm (range, 5–32 mm) below the promontory. The median width of the hypogastric nerve was 3.5 mm (range, 3–4.5 mm) on the right and 3.5 mm (range, 2–6.5 mm) on the left. The median distance from midportion of uterosacral ligament to the closest nerve branch was 0.5 mm (range, 0‐4.5 mm) on right and 0 mm (range, 0‐27.5 mm) on left. In all specimens, the inferior hypogastric plexus was formed by contributions from the hypogastric nerves and branches from S3 and S4. In 47.1% of hemipelvises, S2 branches contributed to the plexus. The sacral sympathetic trunk contributed to the plexus in 16 of 34 hemipelvises where this structure was identified. The inferior hypogastric plexus formed 1–3 cm lateral to the rectum and upper third of the vagina. From this plexus, 1–3 discrete branches coursed deep to the ureter toward the bladder. A uterine branch that coursed superficial to the ureter followed the ascending branch of the uterine artery. An S4 branch was found directly attaching to lateral walls of the rectum in 53% of specimens. Pelvic splanchnic nerves merged into the inferior hypogastric plexus on the lower and medial surface of the coccygeus muscle. Histologic analysis confirmed neural tissue in all tissues that were sampled. CONCLUSION: Anatomic variability and inability to visualize the small caliber fibers that comprise the inferior hypogastric plexus grossly likely underlines the reasons that some postoperative visceral and sexual dysfunction occur in spite of careful dissection and adequate surgical technique. These findings highlight the importance of a discussion with patients about the risks that are associated with interrupting autonomic fibers during the preoperative consent.

Giant cell arteritis of the female genital tract: report of a case and review of the literature.

A 65-year-old female presented with constitutional symptoms of fever and weight loss with bilateral adnexal masses on physical examination. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed and subsequently revealed giant cell arteritis involving numerous small arteries in the ovaries, fallopian tubes, paraovarian and paratubal soft tissues, myometrium, and cervix. After surgery, the patient continued to have constitutional symptoms. Corticosteroid therapy led to a significant improvement and eventual resolution of symptoms. Several similar cases of giant cell arteritis of the female genital tract have been described, both with and without concomitant temporal arteritis. Implications for diagnosis and treatment are discussed.