Neoplastic metastases to the endocrine glands.

Endocrine organs are metastatic targets for several primary cancers, either through direct extension from nearby tumour cells or dissemination via the venous, arterial and lymphatic routes. Although any endocrine tissue can be affected, most clinically relevant metastases involve the pituitary and adrenal glands with the commonest manifestations being diabetes insipidus and adrenal insufficiency respectively. The most common primary tumours metastasing to the adrenals include melanomas, breast and lung carcinomas, which may lead to adrenal insufficiency in the presence of bilateral adrenal involvement. Breast and lung cancers are the most common primaries metastasing to the pituitary, leading to pituitary dysfunction in approximately 30% of cases. The thyroid gland can be affected by renal, colorectal, lung and breast carcinomas, and melanomas, but has rarely been associated with thyroid dysfunction. Pancreatic metastasis can lead to exo-/endocrine insufficiency with renal carcinoma being the most common primary. Most parathyroid metastases originate from breast and lung carcinomas and melanoma. Breast and colorectal cancers are the most frequent ovarian metastases; prostate cancer commonly affects the testes. In the presence of endocrine deficiencies, glucocorticoid replacement for adrenal and pituitary involvement can be life saving. As most metastases to endocrine organs develop in the context of disseminated disease, surgical resection or other local therapies should only be considered to ameliorate symptoms and reduce tumour volume. Although few consensus statements can be made regarding the management of metastases to endocrine tissues because of the heterogeneity of the variable therapies, it is important that clinicians are aware of their presence in diagnosis.

Metastatic pheochromocytoma in MEN 2A: A rare association.

A 45-year-old woman was diagnosed as having multiple endocrine neoplasia type 2A in 2014. She had bilateral pheochromocytoma, medullary thyroid carcinoma and biopsy-proven cutaneous lichen amyloidosis in the interscapular area. She underwent bilateral adrenalectomy; following which, she achieved clinical and biochemical remission. She was planned for total thyroidectomy at a later date; however, she was lost to follow-up. She presented to us again in December 2016 with abdominal pain. Examination revealed hypertension with postural drop. Positron emission tomography scan showed Ga68 and fluorodeoxyglucose (FDG)-avid suprarenal, hepatic, peritoneal and mesenteric masses with abdominal lymph nodes. Twenty-four-hour urinary metanephrines/normetanephrines were elevated. Serum calcitonin was as high as it was 2-1/2 years ago. Ultrasonography-guided fine-needle aspiration cytology (FNAC) from the liver mass revealed neuroendocrine cells that did not stain for calcitonin. Hence, a diagnosis of metastatic pheochromocytoma was made. She underwent total thyroidectomy and was started on cyclophosphamide, vincristine, dacarbazine-based chemotherapy regimen.

Complete metastasectomy for renal cell carcinoma: Comparison of five solid organ sites.

BACKGROUND AND OBJECTIVES: Patients with metastatic RCC can undergo metastasectomy to improve survival time. Our goal was to provide and compare characteristics and oncological outcomes of RCC patients who underwent complete metastasectomy at a single organ site. METHODS: A total of 138 RCC patients were identified as undergoing complete metastasectomy at a single organ site including adrenal, lung, liver, pancreas, or thyroid. Competing risk regression analysis was used to assess RFS and CSS adjusting for several covariates. RESULTS: In this highly selected cohort, RFS and CSS was 27% and 84% at 5 years following metastasectomy, respectively. Univariate analysis revealed that removal of multiple tumors, younger age, and a shorter interval between nephrectomy and metastasis was associated with worse RFS. Larger tumors and sarcomatoid histology at nephrectomy was associated with worse CSS. We found no evidence that metastases at the time of RCC diagnosis influenced recurrence or survival. Tumor size, number of metastases resected, and time from nephrectomy to first recurrence was significantly different, but recurrence rates were not found to be significantly different, when compared across all organ sites. CONCLUSIONS: These findings inform clinical and surgical management of select RCC patients with isolated metastasis to one of several organ sites. J. Surg. Oncol. 2016;114:375-379. © 2016 Wiley Periodicals, Inc.

Imaging of metastases from breast cancer to uncommon sites: a pictorial review.

There are three types of breast cancer recurrence which can occur after initial treatment: local, regional, and distant. Distant metastases are more frequent than local and regional recurrences. It usually occurs several years after the primary breast cancer, although it is sometimes diagnosed at the same time as the primary breast cancer. Although the common distant metastases are bone, lung and liver, breast cancer has the potential to metastasize to almost any region of the body. Early detection and treatment of distant metastases improves the prognosis, therefore radiologists and clinicians should recognize the possibility of metastasis from breast cancer and grasp the imaging characteristics. In this report, we demonstrate the imaging characteristics of metastases from breast cancer to uncommon sites.

Immunohistochemical expression of somatostatin receptors in digestive endocrine tumours.

INTRODUCTION: Somatostatin receptors are expressed in a large number of human tumours. The somatostatin receptors types 1-5 expression in a series including 100 gastro-entero-pancreatic endocrine tumours were analysed. METHODS: From a prospectively built database of patients with gastro-entero-pancreatic endocrine tumours referred from three institutions, 100 cases with clinical and pathological data were selected. Somatostatin receptors expression by immunohistochemistry with somatostatin receptor types 1-5 antibodies in tissue paraffin sections were studied and correlated with the histological diagnosis according to the WHO classification, location and functional status. RESULTS: Of the 100 cases, 67 were gastrointestinal tumours, 25 pancreatic and 8 liver metastasis of unknown origin. Thirty-one of them were functioning tumours: 2 insulinomas, 5 gastrinomas, 1 glucagonoma and 23 carcinoids. Somatostatin receptors expression was observed in 94 tumours. The six negative cases were all non-functioning tumours. Somatostatin receptors 2a and 5 were highly expressed (86 and 62%, respectively), and surprisingly found even in poorly differentiated endocrine carcinomas. Somatostatin receptors expression was less frequent in pancreatic than in gastrointestinal tumours. Well-differentiated neoplasms had a higher density of somatostatin receptors. Only SSTR2a showed membrane staining. CONCLUSIONS: Immunohistochemistry revealed that somatostatin receptors were highly expressed in both primary and metastatic gastro-entero-pancreatic endocrine tumours with heterogeneous staining distribution. It proved to be a reliable technique even in small tumour samples.

Survival and prognostic factor analysis in patients with metastatic pancreatic endocrine carcinomas.

OBJECTIVES: Pancreatic endocrine carcinomas (PECAs) are uncommon, with an incidence of 1 per 100,000. Past studies of chemotherapy and hepatic arterial embolization have described median survival durations of approximately 2 to 3 years. Overall survival from time of diagnosis of metastases has never been reported in a large cohort of patients. Our objective was to evaluate the stage-specific prognosis of patients with metastatic PECAs and to assess the impact of clinical and pathologic prognostic factors. METHODS: We evaluated all cases of differentiated, metastatic PECAs seen at the H. Lee Moffitt Cancer Center between the years 1999 and 2003, measuring survival from time of diagnosis of metastases. RESULTS: Ninety cases of metastatic PECAs were identified. Median overall survival was 70 months, and the 5-year survival rate was 56%. Age, sex, and tumor type (functional vs nonfunctional) did not impact prognosis. Tumor grade, however, was highly prognostic for survival. CONCLUSIONS: Median overall survival is 70 months (5.8 years) among patients with metastatic PECAs. This prolonged survival duration may reflect the impact of multimodality treatments. Tumor grade (low vs intermediate grade) represents a highly significant prognostic factor.

Well-differentiated endocrine carcinoma of the renal pelvis: report of a case with sustained objective response to octreotide.

Endocrine tumors of the upper urogenital tract are extremely rare. We report the case of a patient with a primary well-differentiated endocrine carcinoma of the renal pelvis metastatic to the liver, in whom an objective response was obtained under octreotide treatment. A 36-year-old woman without symptoms was admitted for exploration of a solid nodule in the right kidney. A right nephrectomy was performed. The histological examination of the surgical specimen diagnosed a primary well-differentiated endocrine tumor of the renal pelvis. Tumor cells strongly expressed synaptophysin and were focally positive for chromogranin A; they displayed faint reactivity for PSAP. Three months later, multiple liver metastases, proved by biopsy, were diagnosed. After two lines of chemotherapy, octreotide treatment was initiated because of persistent high activity at scintigraphic examination. A marked decrease in tumor volume and in chromogranin A serum levels was obtained. Two years later, there was no further progression. The patient was treated with octreotide. Our report points out the unusual immunophenotypic features which may be encountered in well-differentiated endocrine carcinoma of the upper urogenital tract and the potential interest in somatostatin analogues in the treatment of metastatic cases.

Placental site trophoblastic tumor with multiple metastases and complete response to salvage BEP regimen: a case report and review of the literature.

Placental site trophoblastic tumor is a rare form of gestational trophoblastic disease, derived from invasive implantation site (intermediate) trophoblastic cells. It is frequently resistant to chemotherapy. Patients with metastases, however, frequently have progressive disease and die despite surgery and multiagent chemotherapy. In this case, a 24-year-old woman was referred because of intermittent vaginal bleeding episodes for 5 months following delivery. Multiple metastases in lungs, liver, kidneys, breast, pancreas, and adrenal and thyroid glands were detected. Combination therapy including surgery and multiagent chemotherapy was planned. Hysterectomy and pelvic lymph node dissection were performed. All metastatic lesions disappeared with EMA-CO treatment. However four courses of BEP regimen, salvage therapy, was performed for plateauing hCG level. Surgery and multiagent chemotherapy seem mainstay of treatment of cases having multiple metastases of PSTTs.

Transarterial chemoembolization of liver metastases from well differentiated gastroenteropancreatic endocrine tumors with doxorubicin-eluting beads: preliminary results.

PURPOSE: To evaluate the feasibility, safety, and efficacy of transarterial chemoembolization (TACE) of progressive liver metastases from well differentiated gastroenteropancreatic endocrine (GEP) tumors with drug-eluting beads (DEBs). MATERIALS AND METHODS: From June 2004 to July 2005, eight men and 12 women aged 34 to 75 years (mean +/- SD, 59 y +/- 12), including 13 patients with bilobar disease and seven with unilobar disease, underwent 34 sessions of TACE with DEBs (500-700 mum) loaded with doxorubicin. Morphologic response was evaluated with computed tomography (CT) at 1 and 3 months according to Response Evaluation Criteria In Solid Tumors. Clinical and laboratory data were also assessed. RESULTS: The complete dose of 4 mL of DEBs loaded with 100 mg doxorubicin was injected during 22 TACE sessions and 1-3.5 mL of DEBs was injected during 12 TACE sessions. Three months after TACE, 16 of 20 patients (80%) exhibited a partial response, three (15%) had stable disease, and one (5%) had progressive disease. The mean size of the largest metastasis in each patient decreased from 42 mm +/- 24 before treatment (median, 39.5 mm) to 33 mm +/- 23 (median, 29 mm) 1 month after treatment and 30 mm +/- 21 (median, 26.5 mm) 3 months after treatment. After a median follow-up of 15 months (range, 6-24 months), nine patients' disease remained controlled without tumor progression and 10 patients had progressive disease. The median time to progression was 15 months. Postembolization syndrome lasted less than 7 days in 23 sessions (67%) and more than 7 days in seven sessions (22%), and no symptoms at all were observed in four sessions (11%). Peak aspartate aminotransferase, alanine aminotransferase, and bilirubin levels after TACE were 35-490 IU (mean, 125 IU +/- 77; normal, <35 IU), 20-440 IU (mean, 149 IU +/- 155; normal, <45 IU), and 8-90 mol/L (mean, 26 IU +/- 25; normal, <17 IU), respectively, at 2-3 days. In five patients, follow-up CT at 1 month revealed TACE-induced peripheral liver necrosis. CONCLUSIONS: TACE with DEBs is well tolerated and appears effective. A comparative study with a standard TACE or transarterial embolization regimen is warranted to define the best protocol for transarterial treatment of GEP liver metastases.

Predictors of long-term survival after liver transplantation for metastatic endocrine tumors: an 85-case French multicentric report.

Liver transplantation (LTx) for metastatic endocrine tumors (MET) remains controversial due to the lack of clear selection criteria. From 1989 to 2005, 85 patients underwent LTx for MET. The primary tumor was located in the pancreas or duodenum in 40 cases, digestive tract in 26 and bronchial tree in five. In the remaining 14 cases, primary location was undetermined at the time of LTx. Hepatomegaly (explanted liver > or =120% of estimated standard liver volume) was observed in 53 patients (62%). Extrahepatic resection was performed concomitantly with LTx in 34 patients (40%), including upper abdominal exenteration (UAE) in seven. Postoperative in-hospital mortality was 14%. Overall 5-year survival was 47%. Independent factors of poor prognosis according to multivariate analysis included UAE (relative risk (RR): 3.72), primary tumor in duodenum or pancreas (RR: 2.94) and hepatomegaly (RR: 2.63). After exclusion of cases involving concomitant UAE, the other two factors were combined into a risk model. Five-year survival rate was 12% for the 23 patients presenting both unfavorable prognostic factors versus 68% for the 55 patients presenting one or neither factor (p < 10(-7)). LTx can benefit selected patients with nonresectable MET. Patients presenting duodeno-pancreatic MET in association with hepatomegaly are poor indications for LTx.

Treatment with combined streptozotocin and liposomal doxorubicin in metastatic endocrine pancreatic tumors.

UNLABELLED: Treatment with combined streptozotocin and liposomal doxorubicin is safe and efficient in patients with endocrine pancreatic tumors (EPTs). No cardiac toxicity was reported. BACKGROUND: The combination of streptozotocin and doxorubicin has been shown to be superior to streptozotocin and fluorouracil in the treatment of metastatic EPTs. However, the risk of cardiac toxicity from anthracyclins hampers the usefulness of the drug combination. Liposomal doxorubicin has a lower frequency of cardiac adverse events compared to doxorubicin. We wanted to assess the efficacy and safety of combined streptozotocin and liposomal doxorubicin in patients with metastatic EPTs. METHODS: Thirty patients with metastatic EPTs were recruited from three medical centers in Norway and Sweden during a time period of 3 years. All patients had histopathologically confirmed diagnoses and bidimensionally measurable lesions. 30 mg/m(2) of liposomal doxorubicin was administered on day 1 of each cycle. During the first course, 1 g of streptozotocin was given on 5 consecutive days. Thereafter, 2 g of streptozotocin was given on day 1 only. Treatment was repeated every 3 weeks. RESULTS: Twelve of 30 patients (40%) achieved an objective radiological response with a median duration of 9 months. Stabilization of disease was achieved in 17 of 30 patients (57%) for a median duration of 11 months. Only one patient had progressive disease as best response. The 2-year progression-free survival was 18% and the 2-year overall survival was 72%. The treatment was well tolerated. None of the patients experienced cardiac toxicity. CONCLUSION: We conclude that combined streptozotocin and liposomal doxorubicin is a safe and efficient treatment for EPTs. The efficacy seems to be comparable to that of combined streptozotocin and doxorubicin, whereas the cardiac toxicity clearly favors using the liposomal drug combination.

[Imaging strategy for staging and follow-up of endocrine tumors]. / Stratégie d'explorations radiologiques pour le bilan d'extension et la surveillance des tumeurs endocrines.

Endocrine tumours constitute a homogeneous network of tumours scattered in the body and characterized by several common features including their capacity to secrete hormones, their association as part of inherited syndrome and their ability to be explored either by functioning imaging than by morphological imaging. However, they have a broad and initially misleading clinical spectrum. Staging of these tumours must be multidisciplinary with the association of primary tumour exploration, staging and follow-up. It also contribute to the screening of complications due to hormonal secretions, the exploration of inherited syndromes and a second cancer diagnosis. First we review the technical characteristics of each imaging modality including morphological imaging (computed tomography, magnetic resonance imaging), metabolic imaging (somatostatin receptors scintigraphy, PET-scan), endoscopy and vascular imaging. Then we review for each endocrine tumour localization and clinical presentation, the imaging strategy as well as the most common morphological and functional features.

Asymptomatic calcitonin-secreting tumor of the pancreas. A case report.

CONTEXT: Pancreatic endocrine tumors are unusual tumors arising from cells belonging generically to the amine precursor uptake and decarboxylation system. CASE REPORT: We present a case of a calcitonin-secreting pancreatic endocrine tumor in a 59-year-old male who presented at our Center with elevated calcitonin values. The patient was asymptomatic. Further investigation revealed a tumor, 80 mm in diameter, in the pancreatic body and tail along with three metastatic lesions in segments III, V, and VIII of the liver. Following a distal pancreatectomy, splenectomy and wedge resection of segments III and V along with radiofrequency ablation of the segment VIII lesion, his serum calcitonin reached normal values. CONCLUSIONS: Calcitonin-secreting pancreatic endocrine tumors are often malignant and have a poor prognosis. We believe that an aggressive surgical approach may improve survival.

Hyperandrogenism in a postmenopausal woman presenting with a metastatic ileum endocrine tumor.

OBJECTIVE: To elucidate the mechanism of the hyperandrogenism found in a postmenopausal woman presenting an ileum endocrine tumor with ovarian metastases. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A postmenopausal woman was referred for hirsutism. Basal plasma testosterone was high, 6.6 nM/L (normal,

[Unusual metastases of breast cancer]. / Métastases inhabituelles du cancer du sein.

The breast cancer is the common cancer in female. The metastasis may occur any where in the body. The common sites are in the lymph nodes, the bones, the chest, the liver and the brain. Other sites of metastasis have little importance, rarely researched and constitute the objective of this article.

Endocrine organ metastases in subjects with lobular carcinoma of the breast.

OBJECTIVE: To define the frequency and pattern of endocrine organ metastases in patients dying of invasive lobular carcinoma. DESIGN: Postmortem microscopic evaluation of the ovaries and adrenal, pituitary, thyroid, and parathyroid glands for breast cancer metastases. SETTING: Roswell Park Cancer Institute, Buffalo, NY, between 1971 and 1990. SUBJECTS: One hundred eighteen subjects who died of their cancer: 86 had infiltrating ductal carcinoma; 32, invasive lobular carcinoma. MEAN OUTCOME MEASURE: Quantitative measurements to allow frequency determinations and statistical comparisons. RESULTS: Endocrine organ metastases were found in 91% of the subjects with invasive lobular carcinoma vs 58% of subjects with infiltrating ductal carcinoma. The adrenal gland was most frequently involved. Multiple endocrine metastases were most common in the group with invasive lobular carcinoma. CONCLUSIONS: A relationship exists between invasive lobular carcinoma and endocrine metastases. This indicates that antemortem endocrine evaluation may subsequently improve quality-of-life treatment.

Prospective study of aggressive resection of metastatic pancreatic endocrine tumors.

BACKGROUND: Because metastatic pancreatic endocrine tumors (MPET) have a poor prognosis, 17 patients with potentially resectable MPET were prospectively studied to define the efficacy of aggressive resection. METHODS: Patients underwent resection when the full extent of MPET was deemed operable after imaging studies were obtained. Two patients underwent three reoperations for recurrent tumor. RESULTS: MPET were completely excised in 16 of 20 cases by major resections of liver, viscera, and nodes, with no operative mortality. Survival was 87% at 2 years and 79% at 5 years with mean follow-up of 3.2 years. Median imaging disease-free interval was 1.8 years, and four of 17 patients remain biochemically cured. After aggressive resection patients with MPET limited in extent had higher survival than patients with extensive MPET (p < 0.019). In a nonrandomized cohort of 25 patients with inoperable tumor, survival was 60% at 2 years and 28% at 5 years. CONCLUSIONS: In select patients MPET can be resected safely with a favorable outcome; most patients will experience recurrence, but some may be cured. Resection of extensive MPET does not appear to improve survival. Resection of limited MPET should be considered as life-extending and potentially curative therapy.