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.

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.

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.

Uterine leiomyosarcomas and benign smooth muscle tumors: usefulness of nuclear DNA patterns studied by flow cytometry.

Flow cytometry was used to determine the DNA ploidy pattern of paraffin-embedded archival tissue specimens from 90 surgically resected uterine smooth muscle tumors (49 leiomyosarcomas and 41 leiomyomas). The technique of Hedley was used for preparation of paraffin-embedded tissue into single dissociated nuclei, and the method of Vindeløv was used for staining with propidium iodide. Among the 41 leiomyomas, most tumors (88%) had a DNA diploid pattern; the exceptions were two DNA tetraploid/polyploid and three DNA aneuploid samples. The DNA histograms of the 49 leiomyosarcomas (including 6 epithelioid leiomyosarcomas) were classified as follows: 9 cases (18%) exhibited a DNA diploid pattern, 29 cases (59%) had a DNA tetraploid/polyploid pattern, and 11 cases (23%) had DNA aneuploid peaks. Although DNA ploidy pattern cannot be used diagnostically to distinguish malignant from benign uterine smooth muscle tumors, the nuclear DNA ploidy pattern is an easily measured, objective determination that may have important prognostic significance for patients with uterine leiomyosarcomas.

Immature ovarian teratoma: a review of 14 cases.

We conducted a clinical and pathologic review of 14 patients with immature ovarian teratoma. In this series of patients, one had monodermal malignant neuroectodermal teratoma and two others had immature ovarian teratoma in association with immature presacral teratoma. Because of the small number of cases of immature ovarian teratoma and the diverse therapeutic modalities used in this study, we cannot recommend a specific treatment for patients with this tumor on the basis of our findings. The histologic grade of the tumor seemed to be a reliable indicator of prognosis. Grade 0 metastatic lesions should be considered benign and are associated with a favorable prognosis.

Small-bowel obstruction secondary to endometriosis.

Though endometriosis is a frequent finding in females, it rarely causes obstruction of the small bowel. However, 11 patients with such obstruction were seen at the Mayo Clinic in the years 1950 through 1970. Their ages ranged from 27 years to 51. A portion of involved bowel had to be resected in every case, but most of the lesions were single. Generally the obstructions were subacute and did not produce surgical emergencies. But because the symptoms were neither specific nor acute, the diagnosis seldom was established prior to laparotomy and the majority of the resections were performed without bowel preparation. Nevertheless, morbidity was minor in most cases and there was no mortality. Small-bowel obstruction has not recurred. Endometriosis of the small bowel tends to be limited to the serosa and the muscular coats, not penetrating the mucosa; and obstruction is due to fibrosis and kinking of the bowel. The obstructed segment usually must be resected. If pelvic endometriosis is minimal, no further surgery is necessary. But if the pelvic lesions are extensive, or if multiple sites in the small and large intestines are involved, then more radical resection and bilateral oophorectomy are indicated.

Linitis plastica caused by metastatic lobular carcinoma of the breast.

We describe herein the syndrome of linitis plastica caused by metastatic lobular carcinoma of the breast. In 14 of our 31 patients, gastric involvement, alone or concurrent with other metastasis, provided the first sign of tumor dissemination. The distinction of primary and secondary gastric malignancies in patients with a history of breast cancer is most important for successful management of patients. At a time when primary gastric carcinoma is decreasing nationally, an awareness of the association of lobular breast tumors with linitis plastica due to metastases may modify diagnostic evaluation and treatment planning in patients who present with symptoms of this syndrome.

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.

The primary surgical treatment of carcinoma of the breast: a changing trend toward modified radical mastectomy.

To study the effectiveness of a trend at the Mayo Clinic toward modifying the standard radical mastectomy, the 5-year survival of 873 women treated surgically for breast cancer from 1965 through 1968 was evaluated. The observed survival of 534 patients treated by the standard radical mastectomy was 85% when nodes were negative and 56% when nodes were positive. For 339 patients treated by the modified radical mastectomy, the observed survival was 80% and 48% when axillary nodes were negative and positive, respectively. In order to accomplish a more significant analysis of cancer risk and results of the two operative procedures, a relatively homogeneous group of 541 patients was established from the total group. In this homogeneous group, the observed survival of 336 patients treated by the standard radical mastectomy was 86% when nodes were negative and 66% when nodes were positive. For 205 patients treated by the modified radical mastectomy, the observed survival was 84% and 66% when axillary nodes were negative and positive, respectively. When patients were further analyzed and compared according to the extent of axillary-node involvement, age at the time of treatment, grade, size, location, and histopathologic type of tumor, and the use of postoperative irradiation, survival was essentially the same, irrespective of the type of mastectomy performed.

Ovarian leiomyoma with hilus cell hyperplasia that caused virilization.

A 68-year-old woman had noted gradual virilization and depression for 3 years. Examination revealed a 10-cm right pelvic mass. Plasma testosterone was substantially elevated (1,082 ng/dl), but urinary ketosteroid and ketogenic steroid excretion was normal. Laparotomy revealed a 10-cm mass that replaced the right ovary and weighed 210 g. Histologic analysis revealed a leiomyoma and proliferation of hilus cells in the periphery of the mass. The plasma testosterone decreased postoperatively to 45 ng/dl. We believe that this is the first report of an ovarian leiomyoma associated with hilus cell hyperplasia that caused virilization.

DNA ploidy in endometrial carcinoma: major objective prognostic factor.

Paraffin-embedded tissue samples from 256 patients who received primary treatment (surgical staging, reduction of tumor size, and adjuvant therapy based on surgical and pathologic risk factors) for endometrial carcinoma at the Mayo Clinic between 1979 and 1983 were analyzed by flow cytometry to determine DNA ploidy characteristics. Diploid patterns constituted 78% of the cases, whereas aneuploid and tetraploid patterns accounted for 17% and 5%, respectively. Only 10% of patients with diploid tumors had a relapse in comparison with 39% of those with nondiploid lesions (34% with aneuploid; 58% with tetraploid). Significant differences (P less than 0.001) were noted in estimated 4-year progression-free survivals--88% for patients with diploid and 57% for those with nondiploid tumors. Stage, grade, depth of myometrial invasion, histologic subtype, peritoneal cytology, and DNA ploidy all demonstrated independent prognostic significance (P less than 0.001) in this study population. When subjected to multivariate analysis, however, grade and depth of myometrial penetration failed to retain prognostic significance (P greater than 0.15) and surgical stage was marginally significant (P = 0.05), whereas histologic subtype and DNA ploidy maintained significant predictive powers (P less than 0.001 and P less than 0.01, respectively). We conclude that DNA ploidy is a major objective prognostic factor and therapeutic determinant for endometrial carcinoma.

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.

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.

Malignant nonfunctioning paraganglioma of the retroperitoneum producing renovascular hypertension.

Malignant nonchromaffin paraganglioma (chemodectoma) is an unusual tumor arising from chemoreceptor cells derived from the neural crest. Although these tumors generally occur in the head and neck, where the term "carotid body tumor" applies, more than 20 cases of retroperitoneal origin have been described. This case report presents the clinical, radiographic, and pathologic features of a chemodectoma arising in the retroperitoneal area that produced severe hypertension by unilateral real vascular compression. The patient underwent exploratory laparotomy, and a left nephrectomy was done. Follow-up examination 1 year after surgery disclosed no clinical evidence of disease, and he had normal blood pressures without medication.

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.

Ovarian dysgerminoma: a retrospective analysis of results of treatment, sites of treatment failure, and radiosensitivity.

Thirty-five patients with a diagnosis of pure ovarian dysgerminoma underwent assessment at our institution between 1950 and 1984. The median age of these patients was 21 years (range, 8 to 41 years). The surgical pathologic stages of the tumors were as follows: stage IA1 in 18 patients, stage IA2 in 2, stage IB1 in 2, stage IC in 1, stage IIB in 2, stage III in 9, and stage IV in 1. The overall survival at 5, 10, and 20 years was 94.3%, 82.9%, and 82.9%, respectively, for all 35 patients and 100%, 83.9%, and 83.9%, respectively, for the 18 patients with stage IA1 lesions. The maximum interval from diagnosis to relapse was 3.7 years. All patients were under surveillance for a minimum of 2 years (median follow-up, 15.9 years). Of the 18 patients with stage IA1 disease, 16 did not receive prophylactic radiation therapy to the para-aortic lymph nodes, and in 6 of the 16 (38%) recurrent disease developed in this region. Five of these patients were salvaged with radiation therapy and one with radiation therapy and subsequent chemotherapy. No definite correlation was noted between the size or mass of the resected unilateral encapsulated tumor and the risk of development of recurrent disease. For patients with stage IA1 dysgerminoma who have undergone unilateral oophorectomy, two treatment options seem reasonable: (1) observation, with radiation therapy reserved for subsequent recurrence, or (2) prophylactic radiation therapy (2,000 cGy) to para-aortic and ipsilateral common iliac lymph nodes, which would preserve fertility.

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.

Amyloid localized to tenosynovium at carpal tunnel release. Natural history of 124 cases.

One hundred fifty-two patients with amyloid in the tenosynovium who had carpal tunnel release were identified. Twenty-eight patients were excluded because of systemic amyloidosis: primary systemic amyloidosis (AL) in 24, secondary amyloidosis (AA) in 3, and familial amyloidosis (AF) in 1. The remaining 124 patients (82%) had carpal tunnel syndrome with local deposition of amyloid and no evidence of systemic amyloidosis. Median survival of the 124 patients from diagnosis of amyloidosis was 12 years. Only two patients had systemic amyloidosis develop--9 and 10 years after recognition of tenosynovial amyloid. Of particular interest were 12 patients who had an M-protein in the serum or urine. None of the 12 patients have had evidence of systemic amyloidosis or multiple myeloma during the median follow-up of 14 years. The authors conclude that amyloid may be localized to the tenosynovium and that systemic amyloidosis rarely develops during long-term follow-up.

Synchronous and metachronous carcinoma of the breast.

To determine the incidence of synchronous bilateral breast cancer, 100 women receiving their initial treatment for primary breast cancer prospectively underwent biopsy of the opposite breast. No patient had a clinically detectable abnormality in the contralateral breast, but 2% had unsuspected invasive ductal carcinomas. An additional 5% had premalignant lesions. To determine the incidence of the development of metachronous breast cancer, 153 women who underwent surgical treatment of primary breast cancer between 1955 and 1979 were followed from 2 months to 26 years, with an average of 3.6 years. During that time, 3.9% developed metachronous carcinomas of the contralateral breast.

Surgical considerations after chemotherapy and radiation therapy for inflammatory breast cancer.

Eighteen patients seen between 1974 and 1982 with the clinical diagnosis of inflammatory breast carcinoma underwent modified radical mastectomy after preoperative chemotherapy and radiation therapy. In 17 of the 18 patients (94%), residual carcinoma was detected in either the resected breast or the axillary nodes. All mastectomies were accomplished without major technical difficulty. Seven wound complications, including three infections, occurred. Local recurrence was noted in 29% (five of 17 patients) and distant metastasis was detected in 89% (16 of 18 patients). Only three patients are presently alive without evidence of disease 19, 21, and 21 months since the onset of symptoms. Eleven patients have died, the median survival being 23 months since the development of symptoms, and four are alive with distant metastasis. Modified radical mastectomy can be accomplished in patients with inflammatory breast cancer after preoperative chemotherapy and radiation therapy and may have a role in reducing local tumor burden.