Cushing's syndrome secondary to a neuroendocrine tumor: relapse after bilateral adrenalectomy

Bilateral adrenalectomy results in the removal of the site of glucocorticosteroid production thereby eliminating the signs and symptoms of Cushing's syndrome. A case is reported of a middle-aged man with Cushing's syndrome due to an ACTH-producing tumor. The patient initially responded to adrenalectomy but had a fatal relapse. Autopsy showed that the right adrenal bed containing remnants of adrenal tissue. An islet cell carcinoma of the pancreas was thought to be the primary tumor.     

Small cell carcinoma of the uterine cervix showing Cushing's syndrome caused by ectopic adrenocorticotropin hormone production.

A uterine cervical cancer is reported in a woman who developed Cushing's syndrome. The tumor measured 1.3 x 0.7 cm, and was a pure small cell carcinoma, identical to that in the lung. The primary tumor cells showed argyrophilia with Grimelius staining and reacted positively to the anti-chromogranin antibody. Clinically, the neoplasm behaved in an aggressive manner in spite of adjuvant chemotherapy and radiotherapy, and the patient died of widespread metastasis. Cushing's syndrome was noted after the occurrence of liver metastasis with an elevation of the serum adrenocorticotropin hormone (ACTH) level. At autopsy, metastatic tumor cells from the liver reacted immunohistochemically positively not only to anti-ACTH but also to antichromogranin, anti-gastrin and anti-calcitonin antibodies. This is the first report of an immunohistochemical analysis of, and comparison of primary and metastatic sites in cervical carcinoma showing Cushing's syndrome.     

Rapidly progressive primary adenocarcinoma of the lung with signet-ring cells responding to 5-fluorouracil and leucovorin: A case report

A 47-year-old female patient with a tumor mass in the left upper lung was admitted to our hospital. Needle biopsy of the tumor revealed signet-ring cell carcinoma, which is relatively rare in the lung. Since no other primary site was found, she was diagnosed with primary lung adenocarcinoma with signet-ring cells. The primary tumor showed rapid growth. She was first treated with combination chemotherapy consisting of continuous 5-FU infusion, leucovorin, and CDDP. Although the size of the primary tumor was markedly diminished, a new metastatic lesion appeared after chemotherapy. Subsequent continuous 5-FU infusion and leucovorin without CDDP chemotherapy controlled aggressive growth of the primary tumor for several months. This case suggests that 5-FU should be included in the anticancer regimen for primary signet-ring cell carcinoma of the lung.     

肺鳞状细胞癌视网膜转移1例

肺癌是临床上常见的恶性肿瘤,发病率和死亡率居肿瘤首位,严重威胁人类的健康.由于早期缺乏有效的、特异性强的筛查方法,多数患者发现时已处于中晚期,常合并骨、脑、肝、肾上腺等部位的转移.通常,患者多因原发病灶、扩散转移或副肿瘤综合征等引起临床症状而就诊.对由于远处转移相关症状作为首发表现就诊的患者,诊断是一个非常大的挑战.视网膜转移作为肺鳞癌的首发症状极其罕见.本文回顾性分析了我院收治的一例肺鳞癌患者的诊治经过,以眼部症状为首发表现,基于临床表现、影像学检查和手术病理诊断,给予患者手术、化疗等多学科综合治疗,目前短期预后良好,随访观察中.我们总结了本病例诊疗过程的特点,为临床医生提供经验.同时复习肿瘤眼内转移的相关文献,为我们对于肺癌罕见表现的深入了解提供了一个窗口.     

Intensive multimodality therapy including paclitaxel and reduced-intensity allogeneic hematopoietic stem cell transplantation in the treatment of adrenal cancer with multiple metastases

Adrenocortical carcinoma is a rare malignancy in adolescents and young adults. The prognosis of unresectable/metastatic adrenocortical carcinoma remains very poor because the rarity of the tumor has made it difficult to establish treatment guidelines, and diagnosis and the resultant treatment can be greatly delayed. We treated a 24-year-old woman who was diagnosed with adrenocortical carcinoma of the right adrenal gland which extended to the inferior vena cava. Although she underwent surgical resection of the extensive tumor as the primary treatment, the disease recurred in the lung and liver as multiple metastases shortly after surgery. She received intensive multimodality therapy, including chemotherapy with paclitaxel, ifosfamide, and cisplatin (TIP regimen), embolization of the feeding arteries, and proton irradiation for the liver mass. Finally, she underwent reduced-intensity allogeneic hematopoietic stem cell transplantation from an HLA 1-locus-mismatched sibling donor. A prolonged survival of 39 months after the onset of the disease was achieved. Although this experience is limited, we suggest that TIP chemotherapy was effective for adrenocortical carcinoma, and a graft-versus-tumor effect after reduced-intensity stem cell transplantation may have contributed to the prolonged survival.     

A case of virilizing adrenocortical carcinoma in an adult female with increased urinary excretion of catecholamines

We report a rare case of virilizing adrenocortical carcinoma with increased urinary excretion of catecholamines. A 53-year-old woman was admitted because of a huge abdominal mass. A child's-head-size mass was palpable in the right upper quadrant. IVP, CT scan and angiography revealed a characteristic picture of an adrenal tumor. Urinary catecholamines and vanilmandelic acid were increased slightly. The urinary 17 ketosteroid level was very high (59.0 mg per day) and was not suppressed by a dexamethasone test. Exploratory laparotomy revealed that the tumor was fixed and had infiltrated to the vena cava, aorta and liver. Therefore, chemotherapy was performed. The dosage of op'-DDD was increased gradually to 9 g daily. During this treatment, a 5-days' course of treatment with cis-platinum (50 mg/day) was repeated 2 times. This patient achieved partial response according to Koyama-Saito's criteria. However, she died 18 months after the first admission. On autopsy, determined histopathologically that she died of adrenocortical carcinoma arising from the adrenal gland. However systemic lymph node, bone and lung metastases were also revealed. There is a possibility that this tumor secreted both sex steroids and catecholamines.     

转移性肾上腺癌的临床治疗（附15例报告）

目的:分析我院收治的15例肾上腺转移性恶性肿瘤的临床资料，结合文献复习，总结临床诊治体会。方法:回顾性分析我院2011年1月至2019年5月收治的15例肾上腺转移性恶性肿瘤患者的临床资料。男12例，女3例；平均年龄为63岁(53～73岁)。肾上腺转移瘤的最大径中位值为4.4 cm（2.0~9.8 cm），左侧11例，右侧3例，双侧1例。原发恶性肿瘤来源:肺7例，肝3例，肾2例，子宫1例，胰腺1例，腹膜后肿物1例。本研究中15例肾上腺转移恶性肿瘤为原发肿瘤确诊后诊断，距离原发肿瘤诊断的中位时间为15.6个月(5~28个月)。15例患者均行手术切除治疗。结果:术后病理细胞类型:腺癌4例，肝细胞癌3例，透明细胞癌2例，弥漫性大B细胞瘤2例，神经内分泌癌1例，癌肉瘤1例，肺小细胞癌1例，肺大细胞癌1例。术后定期随访患者，15例患者生存4~78个月。患者最终死于肿瘤广泛转移。结论:我院肾上腺转移性恶性肿瘤的原发肿瘤以肺癌最为常见，多数转移瘤在定期复查中无意发现。我院肾上腺转移瘤以左侧多见。肾上腺转移瘤治疗方式有手术治疗、介入治疗、经皮肿瘤消融、免疫治疗、放疗和化疗等。     

Diagnosis and treatment of adrenocortical tumors

Adrenocortical tumors can be divided into two groups based on their histopathological characteristics, i.e., benign (adenoma) and malignant (carcinoma), and also classified as functioning (or hormonal) and non-functioning (or non-hormonal) tumors, depending on the presence or absence of recognizable clinical syndromes due to excessive steroids. The syndrome of functioning adrenocortical tumors includes Cushing's syndrome, primary aldosteronism and the adrenorge genital syndrome, of which a minority presents most of the specific clinical features: Cushing's syndrome; red face, typical moon face, truncal obesity, and purplisch red striae, primary aldosteronism; muscle weakness, noctural polyuria, hypertension and hypokalemia, adrenogenital syndrome; virilization or feminization, but many of them present complete clinical picture. The diagnosis of these syndromes needs to measure urinary 17-OHCS and 17-KS and plasma concentrations of cortisol, aldosterone, dehydroepiandrosterone (DHEA) and the other steroids. Dexamenthasone suppression test, various stimulation tests and the measurement of plasma ACTH are also useful for diagnosis. Usually, adrenocortical tumors can be detected preoperatively by physical examination or radiographic studies. Some are massive enough to be palpable through the abdominal wall. Some are large enough to cause displacement of the kidney, as seen intravenous urography. Most are visible by adrenal scintigraphy using 131I-iodocholesterol, computerized tomography, or adrenal arteriography. The standard treatment for adrenocortical tumors are surgical resection. Unresectable adrenocortical carcinomas may be treated with an adrenocorticolytic drug, o'p'-DDD. Metyrapone and aminoglutethimide can be also employed to inhibit the production of steroids.     

Adrenal endothelial cyst associated with adrenocortical adenoma:a case report and literature review

We present a case of a middle-aged male Chinese patient who was asymptomatic with a large(6×7 cm)right adrenal mass was found in this patient upon routine health examination.He underwent laparoscopic right adrenalectomy after comprehensive evaluation,and the mass was finally diagnosed as right adrenal endothelial(vasculature)cyst associated with adrenocortical adenoma according to pathological and immunohistochemical studies.The puzzling image resemblance of a variation of adrenal cyst to carcinoma necessitated histological examination for confirmative diagnosis.The development of endothelial cyst is extremely rare,and its association with other adrenal neoplasms is even rarer.Herein,we report a new case of adrenal endothelial cyst associated with adrenocortical adenoma,which was almost indistinguishable from adrenocortical carcinoma,and hope that it would be helpful in the diagnosis of other similar cases.     

Treatment of metastatic adrenal cortical carcinoma with cisplatin and etoposide (VP-16)

Two patients with metastatic adrenal cortical carcinoma were treated with cisplatin and etoposide. Both achieved a partial remission after only one cycle. One patient had a "nonfunctioning" tumor that had previously regressed on mitotane whereas the second patient presented with classical Cushing's syndrome. Although the latter patient's urinary 17-ketosteroids normalized while receiving mitotane, the tumor itself failed to regress objectively. Cisplatin plus etoposide appears to be an active combination for the treatment of metastatic adrenal cortical carcinoma.     

Cytomegalovirus associated colonic pseudotumor: a consequence of iatrogenic immunosuppression in a patient with primary brain tumor receiving radiation and temozolomide

We report the case of a patient with primary brain tumor who developed cytomegalovirus associated colonic pseudotumor as an opportunistic infection while receiving chemotherapy with Temozolomide and radiation. This case highlights the potential for severe opportunistic infections in this patient population after severe immunosuppression.     

Diagnosis and treatment of primary adrenal tumors

The authors review 21 articles concerning primary adrenal tumors published in 1989. Specifically, the articles deal with the radiologic evaluation of the adrenal mass, functional evaluation of adrenal tumors, technical and perioperative considerations of adrenalectomy, and adrenocortical carcinoma. Several conclusions can be drawn from these recent articles. First, diagnostic accuracy should improve with advances in magnetic resonance imaging and improvements in fine needle aspiration technology. Second, the size of an asymptomatic nonfunctional adrenal mass requiring removal still remains to be definitively determined. Third, adrenocortical carcinomas are generally curable only if small and localized. Finally, adjuvant treatment regimens for more advanced adrenocortical carcinomas using mitotane, suramin, and conventional multiagent chemotherapy need to be evaluated in randomized trials.     

Adrenal collision tumour comprised of adrenocortical carcinoma and myelolipoma in a patient with congenital adrenal hyperplasia

Adrenal myelolipoma is a benign tumour characterized by the presence of macroscopic fat. Further workup is not necessary if a diagnosis of adrenal myelolipoma is obtained via imaging. We report the first case of adrenal collision tumour comprised of adrenocortical carcinoma and myelolipoma in a patient with bilateral myelolipomas and congenital adrenal hyperplasia. Computed tomography showed a large right adrenal mass consisting of two different components: soft tissue with peripheral heterogeneous enhancement and macroscopic fat. Imaging findings reflected features of both adrenocortical carcinoma and myelolipoma. Although this entity is rare, collision tumour containing an adrenocortical carcinoma component should be suspected if portions of an adrenal mass partially consist of peripheral heterogeneous enhancement.     

Cushing's disease in a child with lymphosarcoma and acute leukemia.

A 6-year-old girl with lymphosarcoma developed Cushing's syndrome. Suppression-stimulation studies verified adrenal hyperfunction secondary to bilateral adrenocortical hyperplasia, and the course suggested the possibility of "ectopic ACTH" production by the neoplasm as the etiology.     

An ectopic ACTH-producing small cell lung carcinoma associated with enhanced corticosteroid biosynthesis in the peritumoral areas of adrenal metastasis

A 60-year-old Japanese male presented with swelling of bilateral cervical lymph nodes was subsequently diagnosed as the late stage of primary small cell lung carcinoma (SCLC). He was then treated with cisplatin and irinotecan as first-line chemotherapy, but hypokalemia with muscle weakness of the bilateral legs became gradually noticeable following two months of effective chemotherapy. A computed tomography (CT) scan revealed enlargement of bilateral adrenal glands and abdominal and mediastinal lymph nodes, though primary lung tumor remained the same in size. An ectopic ACTH-producing syndrome (EAS) was subsequently revealed by the following endocrinological studies. Hypokalemia was clinically improved by the treatment with metyrapone and the second-line chemotherapy with amrubicin for SCLC was started, but the patient died 12 days after the second-line chemotherapy. Post-mortem examination revealed ACTH immunoreactivity in tumor cells of all the metastatic lesions. Non-neoplastic adrenal cortex demonstrated hyperplasia associated with lipid depletion and marked expression of steroidogenic enzymes, especially in cortical cells around tumor infiltration, suggestive of paracrine ACTH stimulation of cortisol production. This is the first report evaluating expression of steroidogenic enzymes in adrenal cortex especially adjacent to the adrenal metastasis in the patients with EAS due to SCLC. These findings suggest that ACTH producing adrenal metastasis can induce EAS more frequently and severely, and that the symptoms and examination of EAS should be monitored carefully in the patients with adrenal metastasis of SCLC.     

Genetic changes in human adrenocortical carcinomas

Recent studies have suggested that loss of heterozygosity at loci on the short arm of human chromosome 11 (11p) may be important in the pathogenesis of benign and malignant adrenal cortical tumors. To test this concept, adrenocortical carcinomas from nine patients and benign adrenal cortical lesions from eight patients were tested for loss of alleles at loci on human chromosomes 11, 13, and 17. All patients with adrenocortical carcinoma whose normal somatic tissues were heterozygous for a locus on chromosome 17p had lost alleles in the tumor. Four of six patients with adrenocortical carcinoma who were heterozygous for one or more alleles on chromosome 11p in normal tissues had lost 11p alleles in the tumor. Three of six patients with adrenocortical carcinoma showed loss of 13q alleles in the tumor. Loss of alleles on chromosomes 11p, 13q, and 17p was observed in primary tumors and metastases but not in adrenocortical adenomas or hyperplastic lesions of the adrenal cortex. One patient with adrenocortical carcinoma had a somatic mutation in the HRAS1 gene in the normal adrenal gland. The consistency of the genetic changes on chromosomes 11p, 13q, and 17p suggests that they are important in the pathogenesis of adrenocortical carcinoma.     

The development of pulmonary adenocarcinoma in a patient with Job's syndrome, a rare immunodeficiency condition

The hyperimmunoglobulin E (HIE) (Job's) syndrome often has it onset in childhood and is characterized by markedly elevated serum IgE levels, chronic dermatitis and recurrent pyogenic infections. Lymphoid malignancies have most commonly been associated with this syndrome while the first case in the literature of carcinoma associated with HIE syndrome was a squamous cell carcinoma of the vulva, described by Clark et al. in 1998. We observed a male patient with Job's syndrome diagnosed at age three who presented with bone pain and a metastatic epithelial tumor of the bone revealed by biopsy. Diagnostic procedures aimed at detecting the primary site showed multiple mediastinal lymph nodes with lung and liver metastases on computed tomography scans and an extradural spinal metastasis at the upper thoracic level on magnetic resonance imaging. Although the patient refused a bronchoscopic procedure, a diagnosis of pulmonary adenocarcinoma was established on the basis of sputum cytology and the clinical aspects of tumor extent. Intravenous corticosteroids and palliative radiotherapy were given for the spinal metastasis. Palliative chemotherapy could not be started because of the patient's poor performance status as well as nosocomial fungal pneumonia and pseudomonal urogenital infection with bacteremia. Despite the antifungal and broad-spectrum antimicrobial treatments, the patient died of pseudomonal sepsis.     

CT and MR imaging of the adrenal glands in cortisol-secreting tumors

Cushing's syndrome (CS), first described by the neurosurgeon Harvey Cushing in the 1930s, is the result of chronic glucocorticoid excess. In patients with adreno-corticotropic hormone (ACTH)-dependent CS, bilateral hyperplasia of the adrenal cortex occurs, while in those with ACTH-independent primary CS, either adrenocortical tumors or primary adrenal hyperplasia can be observed. Cortisol-secreting adrenocortical tumors are more frequently adenomas, while adrenal carcinoma accounts for only 5% of cases. Unfortunately, no reliable endocrinological tests are available and no specific tumor markers exist to differentiate between benign and malignant adrenal tumors, so both computed tomography (CT) and magnetic resonance (MR) imaging studies are currently required to localize and define adrenal lesions. Additional information to conventional imaging can be obtained using 1?F-fluoro-2-deoxyglucose (FDG)-positron emission tomography (PET)/CT, while percutaneous image-guided fine-needle aspiration cytology (FNAC) in some cases has shown a high accuracy in detecting malignancy and in confirming adrenal metastases. New PET tracers with selective affinity for the adrenal tissue are still under evaluation. Multidetector CT scan, with the combination of unenhanced and dynamic scans, represents the single most accurate modality for the detection and the characterization of adrenal adenomas. In these lesions, chemical-shift MR imaging produces a typical loss of signal intensity on out-of-phase breath-hold gradient-echo images in lipid-rich adenomas. For these lesions there is no difference between CT and MR imaging, while MR chemical shift imaging is very helpful in identifying the additional small group of adenomas where intracellular lipid content is minimal.     

Metastatic small cell carcinoma of the lung presenting as pituitary apoplexy and Cushing's syndrome

Summary We describe a woman with metastatic small cell carcinoma of the lung who presented with pituitary apoplexy and hyperprolactinemia. Within seventeen months she developed florid Cushing's syndrome with anasarca, hyperpigmentation, hypertension with marked hypercortisolemia (not suppressible with 8 mg dexamethasone), elevated serum ACTH, hypokalemic metabolic alkalosis, and multiple hepatic metastases. This picture suggested the presence of ectopic ACTH syndrome. She died 26 months after the episode of pituitary apoplexy. Primary small cell carcinoma of the lung was diagnosed post-mortem. Metastases were present in the left lung, regional lymph nodes, heart, liver, bone marrow, sphenoid bone, anterior pituitary and pituitary capsule. Posterior pituitary was normal. There was no evidence of pituitary hyperplasia, of adenoma or of primary pituitary carcinoma. The results suggest the presence of a primary ACTH-producing small cell carcinoma of the lung that metastasized to the parasellar sphenoid bone and then extended to the anterior pituitary and dura to mimic a primary intrasellar cause of pituitary apoplexy and Cushing's syndrome. The case demonstrates how difficult it may be to diagnose the etiology of Cushing's syndrome and it emphasizes a unique variation in the presentation of small cell carcinoma of the lung.     

The case of a person who was revealed by adrenal metastasis of pulmonary pleomorphic carcinoma

We report a case of fifties man. He admitted to our hospital due to a hypochondralgia. Computed tomography revealed a tumor of right adrenal gland and a tumor of upper lobe of the right lung. Adrenal tumor had rapidly increased, so we performed adrenectomy. At first adrenal tumor was diagnosed as primary adrenal cancer because its histological findings did not coincide with those of common histologic types of lung cancer. As there were possibilities that one of adrenal or lung tumor was primary and the other was metastatic or both of the two were double primary, we performed right upper lobectomy. Lung tumor was diagnosed as primary pleomorphic carcinoma containing spindle-shaped tumor cells and adenocarcinoma, and then the diagnosis of adrenal tumor was corrected as metastasis of lung cancer. Two months after the lung operation, cervical lymph node swelling, metastasis of stomach and local recurrence of adrenal tumor appeared. After he underwent six courses of systemic chemotherapy of carboplatin and paclitaxel, a clinical complete response was obtained and no recurrence is observed for 4 years.