Pituitary adenoma: a DNA flow cytometric study of 192 clinicopathologically characterized tumors.

A clinically, immunohistochemically and ultrastructurally characterized series of 192 pituitary adenomas was analyzed for DNA content by flow cytometry. Results were assessed not only relative to tumor immunotype, size, and invasiveness, but also with frequency of recurrence. Case selection was non-random; males predominated (1.8:1) and the ratio of macro-to-microadenomas was 4.2:1. Female patients were slightly younger and, in all adenoma categories, less often had invasive tumors: PRL (15%/30%), ACTH (17%/44%), LH/FSH (8%/27%) and null cell adenomas (0%/27%). With the exception of prolactin cell adenomas, similar proportions of macroadenomas and invasive tumors in all tumor subtypes were diploid and non-diploid. Prolactin adenomas differed in that tumors of males showed a high rate of non-diploidy (65%); such tumors were predominantly macroadenomas, but only 28% were invasive. Among GH-containing tumors 78% were macroadenomas, 40% were nondiploid, and the frequency of invasive macroadenomas was higher (49%) than in PRL tumors (21%). ACTH adenomas were mainly microadenomas (81%), their rate invasion (29%) and of non-diploidy being low (14%). Among "non-functioning" (LH/FSH, null cell adenomas), LH/FSH-producing tumors were all macroadenomas, but with low rates of invasion (23%) and non-diploidy (9%). Null cell adenomas, nearly all macroadenomas, had similar low invasion rate (21%), but were more often non-diploid (39%). In all adenoma subgroups S-phase fractions were higher in non-diploid adenomas by an overall ratio of 2.1:1. Prolactin adenomas showed the highest (15.2%) and LH/FSH adenomas the lowest (5.6%) mean S-phase fraction. When compared to long-term follow-up, neither this parameter nor ploidy correlated with tumor size or invasiveness. Lastly, long-term follow-up showed ploidy to be an unreliable predictor of tumor persistence or recurrence.

Polymorphous low-grade adenocarcinoma of the major salivary glands: report of three cases in an unusual location.

AIMS: Polymorphous low-grade adenocarcinoma (PLGA) is the second most common type of malignant neoplasm in minor salivary glands. Its origin in major salivary glands is considered exceedingly rare. Herein, we present three cases of de novo PLGA arising in major salivary glands. METHODS AND RESULTS: Three cases of PLGA were identified in a large series of primary tumours of major salivary glands. We investigated their clinicopathological profiles, including immunohistochemical features. The three patients (two men and one woman) were 51, 65, and 79 years old. The tumours were 20-30 mm large; two were in the parotid gland and one in the submandibular gland. Histologically, all the tumours had a polymorphous architectural pattern showing predominantly solid, tubular, and cribriform features and invasive growth. Papillary areas were observed focally in two tumours and an 'Indian-file' array in one. The tumour cells had a bland cytological appearance and low mitotic count. Two tumours showed perineural invasion. No preexisting pleomorphic adenoma component was identified. In all cases, tumour cells were positive for epithelial markers, S100 protein, and vimentin but negative for alpha-smooth muscle actin, muscle-specific actin, and glial fibrillary acidic protein. Proliferative activities assessed with the Ki67 labelling index were 4.3%, 7.1%, and 7.6%; no p53 overexpression was observed. Two patients had local recurrence, but none had metastasis or died of tumour. CONCLUSIONS: PLGAs arising in major salivary glands and those in minor salivary glands have similar clinicopathological and immunohistochemical characteristics. It is important to recognize that PLGA can occur ab initio in the major salivary glands, although it is extremely rare.

Extraskeletal myxoid chondrosarcoma: a clinicopathologic, immunohistochemical, and ploidy analysis of 23 cases.

Twenty-three cases of extraskeletal myxoid chondrosarcoma, evaluated at the Mayo Clinic between 1968 and 1996, were studied for clinicopathologic features, immunohistochemical profile, Ki-67 activity, and ploidy status to identify adverse prognostic factors. Females and males were equally affected, and the median age at diagnosis was 50 years. The tumors were located mainly in the lower extremities (83%), and the median tumor size was 9.5 cm. Sixteen tumors showed low cellularity (70%), and eight tumors had high mitotic activity (more than two per 10 high-power fields). The tumors were immunoreactive for vimentin (89%), synaptophysin (72%), epithelial membrane antigen (28%), and S-100 protein (17%). Nine tumors were diploid, three aneuploid, and one tetraploid. Mean Ki-67 activity was 11% (range, 1 to 45%). The 10-year overall survival rate was 78%. On univariate analysis, tumor size > or = 10 cm, high cellularity, presence of anaplasia or rhabdoid features, mitotic activity more than two per 10 high-power fields, Ki-67 > or = 10%, and Ki-67 "hot spot" > or = 25% were associated with decreased metastasis-free or overall survival. Ploidy status was not associated with any adverse outcome. The presence of any of these adverse prognostic factors can indicate the possibility of a more aggressive behavior in extraskeletal myxoid chondrosarcoma, and a closer follow-up is suggested.

Myxoid neoplasms of the adrenal cortex: a rare histologic variant.

The myxoid variant of adrenocortical carcinoma is a rare neoplasm described previously in only two case reports. Because of the rarity of these lesions, the presence of myxoid changes in adrenal cortical neoplasms usually raises the possibility of malignancy. We studied the histopathologic features of 14 cases of myxoid adrenocortical neoplasms, including six adenomas and eight carcinomas. All patients with adenomas with sufficient follow-up (n = 5) were alive with no recurrence of their tumors or evidence of metastatic disease. Four patients with carcinomas died of their disease, two were alive with metastatic disease, and one was alive with no evidence of recurrence or metastatic disease. Histologically, the 14 tumors varied in their myxoid composition, ranging from 10% to 95%. The myxoid foci stained positively with Alcian blue and were usually negative with periodic acid-Schiff and mucicarmine stains. As a group, the immunophenotype of the lesions was typical of other adrenal cortical neoplasms, with positive immunostaining for vimentin, synaptophysin, and alpha-inhibin. One tumor was focally positive for keratin. Myxoid adrenal cortical neoplasms should be included in the differential diagnosis of myxoid retroperitoneal neoplasms. Myxoid changes in adrenal cortical neoplasms may be present in both adenomas and carcinomas, and the usual clinical and histopathologic features for adrenocortical neoplasms should be used to diagnose these neoplasms.

Squamous cell carcinoma of the vulva stage IA: long-term results.

OBJECTIVE: The aim of this study was to evaluate the risk of metastases to lymph nodes and long-term results of radical and modified radical surgery in patients with a T1 squamous cell carcinoma of the vulva and

The diagnosis and incidence of allergic fungal sinusitis.

OBJECTIVE: To reevaluate the current criteria for diagnosing allergic fungal sinusitis (AFS) and determine the incidence of AFS in patients with chronic rhinosinusitis (CRS). METHODS: This prospective study evaluated the incidence of AFS in 210 consecutive patients with CRS with or without polyposis, of whom 101 were treated surgically. Collecting and culturing fungi from nasal mucus require special handling, and novel methods are described. Surgical specimen handling emphasizes histologic examination to visualize fungi and eosinophils in the mucin. The value of allergy testing in the diagnosis of AFS is examined. RESULTS: Fungal cultures of nasal secretions were positive in 202 (96%) of 210 consecutive CRS patients. Allergic mucin was found in 97 (96%) of 101 consecutive surgical cases of CRS. Allergic fungal sinusitis was diagnosed in 94 (93%) of 101 consecutive surgical cases with CRS, based on histopathologic findings and culture results. Immunoglobulin E-mediated hypersensitivity to fungal allergens was not evident in the majority of AFS patients. CONCLUSION: The data presented indicate that the diagnostic criteria for AFS are present in the majority of patients with CRS with or without polyposis. Since the presence of eosinophils in the allergic mucin, and not a type I hypersensitivity, is likely the common denominator in the pathophysiology of AFS, we propose a change in terminology from AFS to eosinophilic fungal rhinosinusitis.

Primary squamous cell cancer of the vulva: radical versus modified radical vulvar surgery.

OBJECTIVE: To evaluate the results of surgical therapy and to specifically compare radical and modified radical vulvar surgery relative to survival, recurrence, metastasis, and complications. METHODS: A retrospective review of 225 patients with primary squamous cell cancer of the vulva was performed. Clinical, pathologic, surgical, and follow-up data were collected from the patient records. All pathology slides were reviewed with a pathologist. Radical surgery included 134 patients treated by the Basset operation. Modified radical surgery accounted for 91 patients with vulvar excision alone (65) or with lymphadenectomy (26) via separate groin incisions. RESULTS: The 5-year recurrence rate was 14%. The overall and disease-free survival rates at 5 years were 76. 1 and 83.4%, respectively. There were no statistically significant differences between the two procedures regarding overall survival, disease-free survival, or the development of recurrence, even after adjusting for stage (P > 0.05). Patients undergoing radical vulvar surgery were more likely to develop surgical complications and sequelae than patients having modified radical surgery, even after adjusting for stage. CONCLUSIONS: Modified radical vulvar surgery is associated with decreased complications and 5-year overall and disease-free survival and recurrence rates similar to those of radical vulvar surgery.

Eclampsia complicating hydatidiform molar pregnancy with a coexisting, viable fetus. A case report.

BACKGROUND: Eclampsia is a rare and serious complication of pregnancy. The occurrence of preeclampsia prior to the 20th week of gestation has been associated with concurrent hydatidiform molar pregnancy. We present a case of eclampsia complicating a partial molar pregnancy associated with a viable fetus. CASE: A 22-year-old white woman, gravida 1, para 0, at 14 weeks' gestation, presented with an excruciating headache associated with hypertension, proteinuria and a viable intrauterine fetus with gastroschisis. Subsequently the patient had a generalized tonic-clonic seizure which resolved with magnesium sulfate therapy. Markedly elevated quantitative human chorionic gonadotropin and a moderately thickened placenta were the sole clinical features suggestive of a molar gestation. Dilation and evacuation was performed revealing unremarkable products of conception. Pathologic and cytogenetic analyses revealed a triploid fetus (69,XXX) consistent with partial molar pregnancy. CONCLUSION: Development of preeclampsia/eclampsia prior to 20 weeks of gestation should prompt a clinical evaluation to exclude the possibility of an underlying hydatidiform molar pregnancy.

Postsurgical changes of the breast that mimic inflammatory breast carcinoma.

OBJECTIVE: To characterize a clinical syndrome that occurs in some women who have undergone breast or axillary lymph node biopsy or partial mastectomy. MATERIAL AND METHODS: Six case reports are presented, the clinical and histopathologic findings are described, and the implications for recognition of this entity are discussed. RESULTS: Patients who had undergone partial mastectomy, breast biopsy, or axillary lymph node excision shortly thereafter had clinical signs (most notably, erythema and edema) suggestive of infectious mastitis or inflammatory breast cancer. Representative histologic sections of involved skin revealed dilated dermal vessels without specific evidence of infection or cancer. Although antibiotic therapy was generally ineffective, the clinical findings resolved with time (from 2 months to 1 year). This condition should be considered in the differential diagnosis when this circumscribed patient population has such intervention-related symptoms. CONCLUSION: This clinical syndrome may mimic an infectious or neoplastic process, but we hypothesize that it is due to interruption of lymphatic vessels. Appropriate recognition may alter the use of antibiotic therapy or surgical intervention.

DNA ploidy of ovarian granulosa cell tumors. Lack of correlation between DNA index or proliferative index and outcome in 40 patients.

BACKGROUND: Most cases of granulosa cell tumor of the ovary are characterized by relatively good outcome; however, some tumors behave aggressively, and some tend to recur many years after the initial diagnosis. Because DNA ploidy has been shown to predict biologic behavior better than conventional prognostic variables in many types of genitourinary tumors, the DNA ploidy of granulosa cell tumors was studied to determine if this test correlates with recurrence or survival. METHODS: Paraffin embedded tissue blocks were available from the primary ovarian tumors of 40 patients. DNA ploidy, percent S-phase fraction, and proliferative index were determined for each sample and were compared with patient outcome. RESULTS: Of the 40 tumors, 33 were DNA diploid, 5 were DNA near diploid/aneuploid, and 2 were aneuploid. The Kaplan-Meier estimate of the probability of tumors not recurring within 5 years postoperatively was 0.907 (95% confidence interval: 0.811, 1.00). CONCLUSIONS: There is insufficient evidence to claim that the DNA pattern is associated with morphology, stage of disease at diagnosis, or tumor size or that either survival or progression free survival differs with respect to any of the conventional prognostic factors considered. However, progression free survival tends to be shorter for those whose maximal tumor dimension was at least 10 cm (borderline significance, P = 0.0597), and survival time tends to be shorter for those with a high proliferative index (P = 0.0008).

Constriction of the umbilical cord by an amniotic band, with fetal compromise illustrated by reverse diastolic flow in the umbilical artery. A case report.

Constriction of the umbilical cord by an amniotic band is a rare entity, associated with a high rate of fetal mortality and congenital anomalies. A case occurred with early detection and successful intervention for fetal compromise caused by the amniotic band, which was associated with first-trimester amniocentesis. This is the first known report of ultrasound Doppler flow studies in a case of umbilical cord constriction by an amniotic band, showing reverse diastolic flow in the umbilical arteries.

Idiopathic inflammatory myopathy of the antisynthetase (Jo-1) type associated with noncaseating granulomas.

The idiopathic inflammatory myopathies are a heterogeneous group of syndromes that share the finding of chronic muscle inflammation. Recently, serologic subtyping of autoantibodies found in patients with these syndromes has been used to identify distinct clinical entities. We describe a 36-year-old woman who, based on the findings of polymyositis documented by both electromyography and muscle biopsy, features of Raynaud's phenomenon, symmetric polyarthritis, "mechanic's hands," and Jo-1 antibody positivity, was considered to have the antisynthetase subset of idiopathic inflammatory myopathy. In addition, the patient had granulomatous synovitis, and noncaseating granulomas were found in a breast nodule. This is the first published report of granuloma formation in the antisynthetase syndrome.

Deoxyribonucleic acid analysis facilitates the pretreatment identification of high-risk endometrial cancer patients.

OBJECTIVE: Our purpose was to assess the proficiency with which cytometrically determined deoxyribonucleic acid variables from pretreatment curettage specimens identify patients at high risk for extrauterine disease or posttreatment relapse. STUDY DESIGN: Flow cytometrically determined deoxyribonucleic acid ploidy, S-phase fraction, deoxyribonucleic acid index, and proliferative index were assessed in 140 paraffin-embedded curettage specimens containing endometrial carcinoma. RESULTS: Although clinical staging identified only 19% of patients with advanced disease, 46% of surgical stages III and IV were aneuploid, 69% had an S-phase fraction > or = 9%, and 69% had a proliferative index > or = 14%. Documented recurrences and cancer-related deaths correlated with nondiploid patterns (29% of 140, 50% of recurrences, 54% of deaths), S-phase fraction > or = 9% (41% of 140, 67% of recurrences, 75% of deaths), and proliferative index > or = 14% (45% of 140, 73% of recurrences, 79% of deaths). Deoxyribonucleic acid index (< 1.5 vs > 1.5) provided additional stratification of aneuploid tumors (p < 0.01). Multivariate analysis identified the proliferative index as the most cogent independent prognostic factor (p < 0.01). CONCLUSION: Deoxyribonucleic acid ploidy and proliferative activity in pretreatment curettage specimens identified the majority of patients at high risk for extrauterine metastasis and relapses.

Peripheral T-cell lymphoma involving the placenta.

BACKGROUND: Placental involvement by maternal malignant lymphoma is a rare complication of pregnancy. METHODS: The case of a 29-year-old woman found to have placental involvement by peripheral T-cell lymphoma (PTCL) diagnosed by morphologic study, immunoperoxidase stains, and molecular genetic studies is reported. RESULTS: The lymphoma was pathologic Stage IVB and although there were no adverse consequences for the child, but the neoplasm progressed rapidly during the postpartum period. CONCLUSIONS: The clinical course suggested that the immunologic changes of the pregnancy exerted a lymphoma-suppressive effect on the lymphoma. The authors know of no other report of a patient with placental involvement by PTCL.

Humoral hypercalcemia associated with a dysgerminoma.

A 16-year-old girl sought medical attention at the Mayo Clinic because of a 4.5-kg weight loss, hypercalcemia, and a pelvic mass. Preoperatively, the level of the beta-subunit of human chorionic gonadotropin was 147 IU/liter. After a brief period for observation and hydration, abdominal exploration revealed a stage III dysgerminoma; total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. Within the dysgerminoma, syncytial giant cells expressed human chorionic gonadotropin-positive immunostaining in the cytoplasm. Postoperatively, the value of the beta-subunit of human chorionic gonadotropin decreased rapidly. The patient received whole-abdomen irradiation 4 weeks postoperatively, after which the level of calcium returned to normal. The patient has been free of disease for more than 7 years.

A genetic review of complete and partial hydatidiform moles and nonmolar triploidy.

Complete and partial hydatidiform moles are genetically aberrant conceptuses. Usually, complete moles have 46 chromosomes (diploidy), all of paternal origin. Most partial moles have 69 chromosomes (triploidy), including 23 of maternal origin and 46 of paternal origin. Triploidy that involves 23 paternal chromosomes and 46 maternal chromosomes is not associated with molar placental changes and, rarely, can result in a live-born infant with multiple birth defects. Herein we review the mechanisms of fertilization that may produce these unbalanced sets of parental chromosomes and the role of genomic imprinting as a possible explanation for these clinical conditions.

DNA ploidy of ovarian dysgerminomas: correlation with clinical outcome.

Abnormal nuclear DNA content, as determined by flow cytometry, when combined with conventional prognostic variables such as tumor grade or stage at diagnosis, appears to identify patients who are at increased risk for recurrence of disease. The DNA content of ovarian dysgerminoma, a tumor that is homologous to testicular seminoma and is found in young women of childbearing age, was studied to determine if there is a correlation between DNA content and outcome. Such information would be useful in selecting treatment regimens and making possible the preservation of childbearing potential in women who are likely to have a good outcome. The specimens from 23 cases of ovarian dysgerminoma seen at our institution between 1950 and 1985 were analyzed by DNA flow cytometry. Five of the tumors were diploid (21%) and nineteen were nondiploid (79%). Patient outcome was not predicted any better by nuclear DNA content than by conventional prognostic variables.

Renal cell carcinoma associated with sarcoidlike tissue reaction.

A 60-year-old man was referred to our institution with the diagnosis of sarcoidosis. Because of several months' complaint of right flank pain and weight loss, the patient had consulted his local physician. After an extensive workup revealed only cholelithiasis, he underwent a cholecystectomy for presumed chronic cholecystitis. At the time of operation, biopsy of several liver nodules and peripancreatic nodes revealed noncaseating granulomas, consistent with sarcoidosis. On initial examination at our institution, the patient had microhematuria. A chest roentgenogram demonstrated multiple pulmonary nodules, an abdominal computed tomographic scan showed an indeterminate left renal mass, and magnetic resonance imaging of the spine revealed abnormal signals in the body of T-12. Open-lung biopsy showed an adenocarcinoma with clear cell features, likely of renal origin. The patient was diagnosed as having a metastatic renal carcinoma associated with a sarcoidlike tissue reaction. Although noncaseating granulomas have been reported in association with other malignant lesions, to our knowledge this is the first report of such an association with renal carcinoma. In addition, this case illustrates several points. First, sarcoidosis is a multisystem disorder with protean extrapulmonary manifestations. In fact, all our patient's findings could have been attributed to sarcoidosis. Second, noncaseating granulomas occur with many types of processes, including infections, chemical exposures, and, as in this case, neoplasms. Thus, noncaseating granulomas are not pathognomonic for sarcoidosis. Third, sarcoidosis is a clinical diagnosis that cannot be based on histologic findings alone.

Primary pulmonary artery sarcoma. A method of resection.

Primary pulmonary artery sarcoma classically presents with symptoms and findings suggestive of acute pulmonary artery occlusion. An angiocentric mass or the finding of spindling neoplasm on needle biopsy should suggest this neoplasm. The rare unilateral location in the present case permitted resection by pneumonectomy. An endarterectomy technique was used to extract loosely adherent tumor-thrombus from the more proximal portions of the left pulmonary artery.