肾上腺皮质嗜酸细胞肿瘤7例临床分析

目的 探讨肾上腺皮质嗜酸细胞肿瘤的临床和病理学特点.方法 回顾性分析7例肾上腺嗜酸细胞肿瘤的临床资料.结果 7例患者中,1例表现为女性男性化,2例表现为皮质醇增多症,4例无特异表现,肿瘤大小1.5 cm×1.5 cm×2 cm～8 cm× 8cm×9 cm,包膜完整,与周围没有粘连.切面为灰黄色,光镜下胞质内含丰富的嗜酸颗粒,细胞无明显异型性和核分裂相.3例免疫组化NSE（＋）、VIM（＋）.7例均诊断为良性肿瘤,手术切除后未见肿瘤复发和转移.结论 肾上腺嗜酸细胞肿瘤有其自身的特点,大多是没有功能的,发现时一般肿瘤体积比较大,应该根据肿瘤的病理学特征进行良恶性鉴别,术后需要随访.     

Flow cytometric analysis of DNA aneuploidy in adrenal tumors]

Nuclear DNA content of paraffin-embedded tissue from 38 adrenal neoplasms and 9 histologically normal adrenal glands was analyzed using flow cytometry. Histological diagnosis of thirty-eight adrenal neoplasms were 3 adrenocortical carcinomas, 20 adrenocortical adenomas and 15 pheochromocytomas. In 33 cases (87%) of the 38 tumors the determination of DNA ploidy was possible. All 9 control specimens showed DNA diploid pattern in DNA histogram. In adrenocortical neoplasms the incidence of DNA aneuploidy was 0% (0 of 17) in adenomas and 100% (2 of 2) in carcinomas. All 17 adrenocortical adenomas which showed DNA diploid pattern are clinically benign. On the other hand, both 2 cases of adrenocortical carcinoma which showed DNA aneuploidy died within 1 year. These data suggest that DNA aneuploidy may be useful as a prognostic factor in adrenocortical neoplasm. With regard to pheochromocytoma, DNA aneuploidy was detected in 4 of 14 patients (29%). However, all 14 cases were clinically benign. In pheochromocytoma DNA aneuploidy was not found to be correlated with prognosis.     

Specificity of a new lipid mediator produced by testicular and peritoneal macrophages on steroidogenesis

Macrophage-derived factor (MDF) is a lipophilic factor produced by rat testicular and peritoneal macrophages that maximally stimulates testosterone production by rat Leydig cells through a steroidogenic acute regulatory protein independent mechanism. The purpose of the present study was to determine whether MDF is also produced by human macrophages, and/or if it acts on human steroidogenic cells. We also studied the tissue-specific functions of MDF by determining if it also acts on steroidogenic cells of the ovary and adrenal glands and, if so, does it require new protein synthesis. It was found that MDF was produced by human peritoneal macrophages, and was capable of stimulating human steroidogenic cells. In terms of tissue specificity, it was found that primary cultures of rat adrenocortical cells respond to MDF with increased secretion of aldosterone and corticosterone, as did rat granulosa cells by producing progesterone. MDF acted in the presence of cycloheximide, indicating that it does not require new protein synthesis. These results indicate that MDF may have significant therapeutic potential and provide a basis for future studies concerning its physiological role in humans. These results further suggest that MDF is not only involved in paracrine regulation of Leydig cells, but also has the potential for the local regulation of steroidogenesis in both granulosa and adrenal cortical cells.     

Virilizing adrenocortical adenoma: in vitro steroidogenesis, immunohistochemical studies of steroidogenic enzymes, and gene expression of corticotropin receptor

BACKGROUND: No reports have yet precisely determined corticotropin (ACTH) responsiveness in virilizing adrenocortical adenoma. METHODS: Five women with an androgen-secreting adrenal adenoma were reviewed. Three of them were examined by in vitro steroidogenesis. Two of these 3 patients were studied by immunohistochemistry of steroidogenic enzymes and for the gene expression of ACTH receptor by Northern blot analysis. RESULTS: In preoperative hormonal determinations plasma and urine androgens had increased. Dexamethasone did not suppress plasma and urinary androgens, nor did ACTH increase them. In vitro steroidogenesis revealed that the adenoma cells produced mainly dehydroepiandrosterone and a small amount of testosterone. ACTH did not increase the in vitro production of androgens. In immunohistochemical staining 5 enzymes involved in adrenal steroidogenesis were all expressed, especially 17 alpha-hydroxylase, which was strongly expressed in tumor cells. ACTH receptor messenger RNA was not detected in virilizing tumor tissues, whereas it was expressed in attached adrenal tissues. CONCLUSIONS: The lack of response to ACTH is the result of a deficiency of ACTH receptor expression in the virilizing tumor cells. Androgens were autonomously produced in adrenal adenoma cells without ACTH regulation.     

Paraganglioma of the ovary: report of three cases of a rare ovarian neoplasm, including two exhibiting inhibin positivity

Paraganglioma is one of the rarest neoplasms to involve the ovary, whether primary or metastatic, with only two previous reports. We describe three examples that occurred in patients 22, 58, and 68 years of age. Two patients had hypertension. Two tumors involved the left ovary and one the right ovary; they ranged from 8 to 22 cm, were solid, and were tan, brown, or yellow. One tumor was confined to the ovary; in the second case, there were tumor deposits on the posterior surface of the uterus and the contralateral ovary; in the other case, there was peri-aortic lymph node involvement and peritoneal deposits. In all cases, however, radiologic investigations did not reveal an alternative primary site. On microscopic examination, all three tumors showed a predominantly nested "zellballen" pattern with groups of cells surrounded by a vascular stroma. Tumor cells largely had abundant granular eosinophilic cytoplasm with, in 2 cases, focal clear cell areas. In 1 case, bizarre tumor giant cells were present. Immunohistochemically, all neoplasms were cytokeratin negative and diffusely positive with neuroendocrine markers. In 1 case, there was an S-100-positive population of sustentacular cells. Two cases were positive for inhibin, one focal and one diffuse, and the other was focally positive for calretinin. Electron microscopy performed in 2 cases revealed dense core neuroendocrine granules. One patient has been followed up for 15 years and is alive and well. Although metastatic spread from an undetected primary outside the ovary cannot be totally excluded for the 2 cases with extraovarian disease, we think that the neoplasms most likely represent primary ovarian paragangliomas. Because various neoplasms in the sex cord-stromal and steroid categories are likely to enter into the differential diagnosis, inhibin and calretinin positivity represents a significant potential diagnostic pitfall. The differential is broad and may include many other ovarian tumors, particularly those with an oxyphilic cell type. Possible theories of histogenesis of primary ovarian paraganglioma include an origin from extra-adrenal paraganglia in the region of the ovary or unidirectional differentiation within a teratoma.     

Adrenal myelolipomatous nodules mimicking adrenal neoplasms: report of three cases

The authors describe three cases of adrenal myelolipoma. In the first two, unilateral adrenal masses, assumed to represent adrenal neoplasms, were found during urologic examination; the correct diagnosis was made by frozen-section examination during operation. The third case involved bilateral adrenal lesions diagnosed at autopsy in a patient suspected to have metastatic cancer. Histologic, immunohistochemical and electron microscopic studies revealed polyclonal lesions composed of hematopoietic cells and fat cells. Radiologic recognition and fine-needle biopsy of these lesions are important to avoid unnecessary surgery in asymptomatic cases. Since the lesions cannot be regarded as true neoplasms, the authors suggest that the name myelolipoma should be replaced by the term myelolipomatous nodule.     

Chondroid chordomas and low-grade chondrosarcomas of the craniospinal axis. An immunohistochemical analysis of 17 cases.

The classification of cartilaginous neoplasms of the craniospinal axis is controversial. Indeed, the very existence of chondroid chordomas has recently been questioned. In an effort to clarify the direction of differentiation of cartilaginous neoplasms of this region, 17 neoplasms obtained from 17 patients with cartilaginous tumors of the craniospinal axis were examined by immunohistochemistry with a panel of antibodies. The panel included antibodies to cytokeratin (CK), epithelial membrane antigen (EMA), vimentin (VIM), S-100 protein, carcinoembryonic antigen (CEA), and type II collagen. Areas with cartilaginous differentiation were present in all 17 neoplasms. These areas were characterized by a matrix of amorphous blue ground substance with lacunae that contained enlarged and slightly atypical cells. This cartilaginous matrix stained strongly for type II collagen. Thirteen of the 17 neoplasms had a biphasic growth pattern in which areas with conventional chordoma were admixed with areas with cartilaginous differentiation. The cells within the cartilaginous components of these 13 neoplasms stained for CK (10 of 12 cases), EMA (10 of 13 cases), VIM (12 of 12 cases), S-100 protein (seven of 12 cases), and CEA (two of nine cases). Similarly, the conventional chordoma components of these same 13 neoplasms stained for CK (12 of 12 cases), EMA (13 of 13 cases), VIM (12 of 12 cases), S-100 protein (nine of 12 cases), and CEA (two of nine cases). The hyaline-appearing areas between the cords and sheets of cells of the conventional chordoma components of these 13 tumors also stained with type II collagen. These 13 tumors with both neoplastic cartilage and conventional chordoma were classified as chondroid chordomas. One of the 17 cases was composed entirely of neoplastic cartilage; however, the cells within the matrix of the cartilage of this neoplasm stained with the epithelial markers (CK and EMA). Based on the presence of epithelial differentiation within this otherwise cartilaginous neoplasm, it was also classified as a chondroid chordoma. In contrast, the remaining three cases without histologic evidence of chordoma differentiation did not stain for CK or EMA, but they did stain for S-100 protein (three of three cases) and VIM (three of three cases). These three tumors were therefore classified as chondrosarcomas. For purposes of comparison, 19 conventional chordomas without cartilage and 29 peripheral chondrosarcomas were also stained. The 19 conventional chordomas stained in a pattern similar to the conventional chordoma components of the chondroid chordomas, whereas the 29 peripheral chondrosarcomas stained in a pattern similar to the three chondrosarcomas of the craniospinal axis.(ABSTRACT TRUNCATED AT 400 WORDS)     

A Child with Adrenocortical Adenoma Accompanied by Congenital Hemihypertrophy: Report of a Case

We report herein the findings of a 7-year-old male child with a ruptured adrenocortical adenoma and congenital hemihypertrophy which was incidentally detected after suffering a trauma. A review of 21 pediatric cases of adrenocortical neoplasms in the literature was made. The patient showed precocious puberty such as pubis and advanced bone age, but an endocrinological examination revealed no definite abnormalities. The right adrenal tumor with hematoma was resected after these evaluations. Adrenocortical adenoma is considered to occur more frequently in female children. However, the incidence of adrenocortical tumors accompanied by congenital hemihypertrophy does not differ between males and females. The outcomes were relatively good, although the observation periods were short in some patients. A large number of patients presented with a tumor and hemihypertrophy on the same side. This finding is of interest when considering the possible association between hemihypertrophy of the organs and tumor proliferation. However, their association in terms of development was unclear. It is necessary for patients with hemihypertrophy to have regular examinations for the possible development of malignant tumors, especially in the kidney, adrenal gland, and liver. Received: November 1, 1999 / Accepted: March 24, 2000     

肾上腺皮质肿瘤212例临床分析

目的提高肾上腺皮质肿瘤的诊治水平。方法报告收治的肾上腺皮质肿瘤２１２例。结果２１２例中原发性醛固酮增多症皮质瘤１４５例，皮质醇症皮质腺瘤２１例，无功能性肾上腺皮质肿瘤４６例。就其临床特点及特殊临床表现进行分析讨论。结论认为对不同肾上腺皮质肿瘤应及时诊断，尽早手术。     

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.     

Malignant melanoma metastatic to the ovary

The clinical and pathologic features of 10 patients with malignant melanoma metastatic to the ovary were studied. Seven were from surgical patients who presented with possible primary ovarian neoplasms and three were autopsy cases. Six had unilateral involvement, and all but one of the metastases were grossly cystic. Two predominant histologic patterns were identified: the more common (six cases) consisted of small oval to spindle-shaped cells with inconspicuous or absent melanin pigment and a focal storiform architecture. Three of these six were initially misinterpreted as ovarian stromal neoplasms. The other four tumors had large epithelioid cells with abundant cytoplasm and melanin pigment, and were readily classified as metastatic melanoma. Six of the seven surgical cases were reactive with antibodies to S-100 protein and vimentin but nonreactive with antibodies to keratin.     

Epithelioid angiosarcoma of the bone: a series of 10 cases

The clinical and pathologic features of 10 epithelioid angiosarcomas of bone were analyzed. There were eight males and two females who ranged in age from 26 to 83 years (mean 62 years). Four tumors were solitary and six were multifocal. In two consultation cases, the submitted diagnosis was metastatic carcinoma. Microscopically, the tumor cells were arranged in solid and infiltrative sheets, and in most cases vascular channels or cystically dilated spaces were present. The neoplastic cells had abundant eosinophilic cytoplasm and large nuclei with open chromatin and prominent eosinophilic nucleoli. Intratumoral hemorrhage, neutrophilic infiltrates, and intracytoplasmic lumina were frequently present. All 10 tumors stained positive for one or more endothelial markers, with CD31 being the most sensitive marker. Seven cases stained positive for cytokeratin. Ultrastructural examination in three tumors confirmed their endothelial differentiation. In the absence of obvious vascular differentiation, abundant intratumoral hemorrhage and intratumoral neutrophils are useful ancillary morphologic features that may suggest a vascular origin. Six patients are dead of disease, one is alive with metastasis, and two patients are currently disease free. Epithelioid angiosarcoma of bone should be included in the differential diagnosis of epithelioid neoplasms of bone, and endothelial markers should be a part of their immunohistochemical analysis to avoid the misdiagnosis of a metastatic carcinoma because of the significant differences in the treatment and clinical outcomes of these entities.     

Metastatic adrenocortical oncocytoma: a case report

With only 51 cases reported in the literature to date, adrenocortical oncocytoma is an exceedingly rare pathological variant of adrenal neoplasms. The first case of metastatic adrenocortical oncocytoma is reported along with an update of the literature. A role for radiotherapy in the palliative setting is demonstrated.     

P-glycoprotein expression and multidrug resistance in adrenocortical carcinoma.

BACKGROUND. The response of adrenocortical carcinoma (ACC) to adjuvant chemotherapy has been disappointing with no significant impact on survival. The normal adrenal cortex has very high levels of P-glycoprotein, an energy-dependent efflux pump of a variety of structurally unrelated chemotherapeutic agents. P-glycoprotein has been implicated as a cause of multidrug resistance in a variety of neoplasms. The purpose of this study was to evaluate P-glycoprotein expression in ACC. METHODS. Eleven patients with ACC had paraffin-embedded tumor evaluated for P-glycoprotein expression. These were analyzed by immunohistochemistry assay with a battery of four anti-P-glycoprotein antibodies (MRK-16, JSB-1, UIC-2, MDR). RESULTS. All eleven cases showed intense, predominantly membrane immunoreactivity for P-glycoprotein. In 10 of the cases, most tumor cells were immunoreactive with at least three antibodies, and six of 11 cases were positive for all four antibodies. In this small series no correlation existed between P-glycoprotein expression and tumor grade, stage of disease, or survival. CONCLUSIONS. All 11 cases of ACC studied showed P-glycoprotein expression, which was similar to the normal adrenal cortex. This possible mechanism of multidrug resistance may help explain the significant chemoresistance seen in ACC.     

Temporal relationships among testosterone production, steroidogenic acute regulatory protein (StAR), and P450 side-chain cleavage enzyme (P450scc) during Leydig cell aging

Previous studies have shown that the capacity of Leydig cells from aged (21-24-month-old) Brown Norway rats to produce testosterone is reduced from young (4-month-old) levels, and that this is correlated with reductions in steroidogenic acute regulatory protein (StAR), peripheral benzodiazapine receptor (PBR), and the levels and activities of the steroidogenic enzymes. The age(s) at which particular changes in the steroidogenic pathway occur, and the relationship of particular changes to reduced testosterone production, are not known. We examined 3 critical components of the steroidogenic pathway, cyclic adenosine monophosphate (cAMP) production, StAR, and P450 side-chain cleavage enzyme (P450scc) in relationship to age-related decreases in testosterone production. Leydig cells isolated from Brown Norway rats of increasing ages (4, 9, 15, and 20 months) were evaluated. The ability of Leydig cells to produce testosterone was reduced at 9 months, although not significantly. Significant reductions in testosterone production were first seen in cells isolated from rats of 15 months of age, and further reductions occurred thereafter. Reduced testosterone was correlated with reductions in StAR, P450scc mRNA, and protein. Significant decline in luteinizing hormone-stimulated intracellular cAMP levels was seen by 9 months, before significant reductions in testosterone, StAR, and P450scc. Further declines in cAMP levels were seen at 15 and 20 months. These studies suggest that age-related reductions in intracellular cAMP may lead to the reduced testosterone production that characterizes aged Leydig cells. This suggestion is supported by recent studies from our lab demonstrating that long-term (3 days) culture of old Leydig cells with dbcAMP restored testosterone production to levels approximating those of young cells.     

Coexistence of three distinct adrenal tumors in the same adrenal gland in a patient with primary aldosteronism and preclinical Cushing's syndrome

A 62-year-old woman was admitted to our hospital because of hypokalemia. Physical examination revealed no signs of excessive adrenocortical steroid production, as are found in Cushing's syndrome. Her plasma renin activity (PRA) was suppressed (0.10 ng/ml per h), and her serum aldosterone level was high (30.0 ng/dl). PRA was not increased after a renin-releasing test. Her plasma adrenocorticotropic hormone (ACTH) level was low (<5 pg/ml), but her serum cortisol level was normal (21.0 μg/dl). Administration of 8 mg dexamethasone did not suppress her plasma cortisol level. Finally, she was diagnosed with clinical primary aldosteronism associated with preclinical Cushing's syndrome. Magnetic resonance image revealed three sequential nodular masses (each 15 mm × 15 mm) in the right adrenal gland. A right adrenalectomy was performed by endoscopy. The three removed tumors appeared to have different characteristics. Microscopic examination revealed that the upper and lower tumors were adrenocortical adenomas, and the middle tumor was a black adenoma. Immunohistochemical staining for the enzymes involved in cortisol biosynthesis suggested that the upper tumor secreted aldosterone, whereas either or both of the two other tumors secreted cortisol. Surprisingly, at 33 years of age, she had been diagnosed with Cushing's syndrome, due to a cortisol-producing adrenocortical adenoma, and she had received a left adrenalectomy. Clinically and pathophysiologically, this was a very rare case.     

Laparoscopic approach to a large adrenocortical oncocytoma: A case report and review of the literature

INTRODUCTIONAdrenocortical oncocytomas are extremely rare tumors, considered to be non-functional and of low malignant potential. Despite the great advance in laparoscopic techniques, there are extremely limited reports of laparoscopic approach of adrenocortical oncocytomas. Herein is presented a challenging case of laparoscopic approach to a large adrenocortical oncocytoma, underlining the safety and feasibility of laparoscopy in the surgical management of these extremely rare adrenal tumors.PRESENTATION OF CASEA 34 year-old male was referred for surgical evaluation after the incidental discovery of a large right adrenal mass, during ultrasound examination due to renal colic. Further imaging evaluation revealed a well circumscribed capsule around the mass was demonstrated, with no evidence of infiltration of the neoplasm to periadrenal tissues. The patient was scheduled for laparoscopic right adrenalectomy, running an uneventful postoperative period. Histopathology revealed the presence of an adrenal oncocytoma.DISCUSSIONRecent studies have demonstrated that approximately one third of adrenocortical oncocytomas are associated with hormonal hypersecretion, as well as that one fifth of them demonstrate malignant biological behavior. From this point of view, there is emerging evidence in favor of the necessity of surgical excision as the treatment of choice. In spite of the progress of laparoscopic surgery, only three cases of laparoscopic excision of these tumors have been reported up to date.CONCLUSIONLaparoscopic surgery offers a safe alternative in confronting adrenocortical neoplasms, even when the biological behavior of the tumors cannot be pre-operatively evaluated in a definite way.     

Assessing Biological Aggression in Adrenocortical Neoplasia

Pathologists are highly skilled at the evaluation of adrenal neoplasms. Occasional adrenocortical tumors can be diagnostically challenging and supplementary tools can assist in these cases. Histologic and molecular studies support a model that includes 2 broad classes of adrenocortical carcinoma with distinct somatic genetic alterations and clinical outcomes. Pathologists should endeavor to grade adrenocortical carcinomas to assign each case into one of these 2 classes. Mitotic grading by mitotic counting and Ki-67 immunohistochemistry represent the most practicable and informative methods currently available.     

肾上腺皮质腺瘤性征异常症的诊治探讨(附5例报告)

目的:探讨肾上腺皮质腺瘤性征异常症的诊断及治疗。方法:回顾性分析1998年1月～2003年12月5例分泌性激素的肾上腺腺瘤的临床资料。根据临床特点及影像学检查,诊断为肾上腺肿瘤,4例开放手术,1例后腹腔镜手术。结果:性征异常消失,术后病理检查证实为腺瘤。随访1～5年无复发。结论:根据临床表现并结合MRI、CT等影像学检查,可做出临床诊断,手术是惟一有效的治疗方法。肾上腺皮质肿瘤的良恶性仅根据肿瘤的病理组织象,也非绝对可靠,只有非肾上腺组织或器官发生同一类皮质癌转移时才是确诊癌的标准。     

Cushing's disease caused by adrenocortical nodular hyperplasia--diagnosis and surgical treatment

Six cases of Cushing's disease, in which perplex diagnostic problem was encountered, were reported. In the endocrinological examination two cases were not suppressed by a high dose of dexamethasone (8 mg), and the other four cases showed complicated clinical findings due to adrenocortical nodular hyperplasia. Among those four cases with adrenocortical nodular hyperplasia two of them were of functionally autonomic and showed different attitude in responding endocrine assay. When the serum cortisol is not suppressed by a high dose of dexamethasone, differential diagnosis from other causes, such as Cushing's syndrome due to adrenocortical macronodular hyperplasia, becomes quite important for surgical treatment. Usually plasma ACTH in the case of Cushing's disease is slightly increased over the normal range and, on the other hand, it is lower than normal value in the case of Cushing's syndrome due to autonomic adrenocortical nodular hyperplasia because of negative feed back phenomenon. However, in some cases of Cushing's disease plasma ACTH is within normal range or even lower than normal level, and, furthermore, it is not extremely unusual to find a case of adrenocortical macronodular hyperplasia with slightly increased plasma ACTH level over normal range. Those cases offer particularly complex problem in making diagnosis and therapeutic indication. According to our clinical experiences with those six cases, selective venous sampling is found quite useful in differentiating Cushing's disease from other causes and ACTH value in selective venous sampling from inferior petrosal vein is remarkably increased in the cases due to pituitary ACTH secreting adenoma. Cushing's disease with adrenocortical nodular hyperplasia reduces the ACTH value in the sampling to the lower normal range as the adrenocortical nodular hyperplasia progresses.(ABSTRACT TRUNCATED AT 250 WORDS)