Medullary thyroid carcinoma - Adverse events during systemic treatment: risk-benefit ratio

ABSTRACT Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating from parafollicular C cells of the thyroid and associated with mutations in the proto-oncogene REarranged during Transfection (RET). The prognosis of MTC depends on clinical stage, with a 95.6% 10-year survival rate among patients with localized disease and 40% among patients with advanced disease. Standard chemotherapy and radiotherapy have no significant impact on the overall survival of these patients and two tyrosine kinase receptor inhibitors (TKIs), vandetanib and cabozantinib, have been recently approved for the systemic treatment of locally advanced or metastatic MTC. However, since patients with MTC and residual or recurrent disease may have an indolent course with no need for systemic treatment, and since these drugs are highly toxic, it is extremely important to select the patients who will receive these drugs in a correct manner. It is also essential to carefully monitor patients using TKI regarding possible adverse effects, which should be properly managed when occurring.

Small cell neuroendocrine carcinoma of the nasopharynx: a rare case report

Small cell neuroendocrine carcinoma rarely appears primarily in the head and neck and exhibits aggressive behavior with a poor prognosis. The pathologist has a significant role in the diagnosis, and a consensual treatment still does not exist. The authors report the case of a middle-aged male patient who presented repeated episodes of massive epistaxis. The diagnostic work-up disclosed the diagnosis of small cell neuroendocrine carcinoma of the nasopharynx. The patient was treated with chemotherapy followed by radiotherapy. Imaging examinations performed after the end of treatment showed apparent complete remission of the disease. The patient was kept under active surveillance with no signs of local relapse or distant metastasis after 4 years of follow-up.

Rapid response of hypercortisolism to vandetanib treatment in a patient with advanced medullary thyroid cancer and ectopic Cushing syndrome

Medullary thyroid carcinoma (MTC) may rarely present with paraneoplastic syndromes. Among the most frequent ones are the appearance of diarrhea and ectopic Cushing syndrome (ECS). The ECS in the context of MTC is usually present in patients with distant metastatic disease. The use of drugs such as ketoconazole, metyrapone, somatostatin analogs and etomidate have been ineffective alternatives to control hypercortisolism in these patients. Bilateral adrenalectomy is often required to manage this situation. Recently, the use of tyrosine kinase inhibitors has been shown to be a useful tool to achieve eucortisolism in patients with metastatic MTC and ECS. We present a patient with sporadic advanced persistent and progressive MTC with lymph node and liver metastases, which after 16 years of follow-up developed an ECS. After one month of 300 mg/day vandetanib treatment, a biochemical and clinical response of the ECS was achieved but it did not result in significant reduction of tumor burden. However the patient reached criteria for stable disease according to response evaluation criteria in solid tumors (RECIST 1.1) after 8 months of follow-up.

Ectopic Cushing's syndrome caused by a pulmonary ACTH-secreting tumor in a patient treated with octreotide / Síndrome de Cushing ectópico causado por um tumor pulmonar secretor de ACTH em tratamento com octreotide

Ectopic ACTH syndrome is a rare disease often associated with severe hypercortisolism. When feasible, optimal management is surgical excision of the tumor. A 33-year-old male patient was admitted to the hospital in 1993 with clinical manifestations suggestive of Cushing's syndrome. He presented high plasma ACTH and markedly elevated urinary free cortisol excretion that was not suppressed with high-dose dexamethasone administration. Pituitary MRI scan was normal. No central-to-peripheral ACTH gradient was present in bilateral inferior petrosal sinus sampling. Thoracic CT scan showed a 1.7 cm nodule at the left lung. Pulmonary fine needle cytology and immunocytochemical and ultrastructural studies, together with the presence of bone metastases, led to the diagnosis of an ACTH-producing neuroendocrine carcinoma. He was initially submitted to chemotherapy and has been on treatment with octreotide LAR since 1998, having shown a favorable clinical, biochemical and imaging response. We highlight the excellent long-term response to medical therapy with octreotide LAR, without tachyphylaxis, probably due to its antiproliferative effect.

A secreção ectópica de ACTH é uma síndrome rara associada habitualmente à hipercortisolemia grave. A remoção cirúrgica do tumor é o tratamento de primeira linha, sempre que seja exequível. Homem com 33 anos, internado em 1993 com manifestações clínicas sugestivas de síndrome de Cushing, apresentava valores elevados de ACTH plasmática e excreção urinária de cortisol livre muito aumentada, sem supressão na prova com dose alta de dexametasona; RM hipofisária sem alterações; cateterismo bilateral dos seios petrosos inferiores sem gradiente central-periférico de ACTH. A CT de tórax mostrou um nódulo de 1,7 cm no pulmão esquerdo. O diagnóstico de carcinoma neuroendócrino produtor de ACTH foi feito com base nos resultados citológico, imunocitoquímico e ultraestrutural, juntamente com a presença de metástases ósseas. Foi inicialmente submetido à quimioterapia e encontra-se em tratamento com octreotide LAR desde 1998, apresentando resposta clínica, bioquímica e imagiológica favorável. Destacamos a excelente resposta a longo prazo à terapêutica com octreotide LAR, sem taquifilaxia, provavelmente devido ao seu efeito antiproliferativo.

Bloqueo androgénico total en el manejo del cáncer de próstata neuroendocrino / Androgen-deprivation therapy in the management of neuroendocrine prostate cancer

Introducción: El carcinoma prostático neuroendocrino constituye menos de 1 % de las neoplasias prostáticas, con menos de 200 casos en la literatura. El objetivo de esta investigación fue describir la experiencia en el manejo del carcinoma neuroendocrino de próstata con bloqueo androgénico total. Material y métodos: Estudio retrospectivo, descriptivo y observacional, en el que se revisaron los expedientes de pacientes con sospecha de cáncer de próstata sometidos a biopsia transrectal o resección transuretral de próstata, de enero de 2000 a diciembre de 2007. Fueron seleccionados pacientes con diagnóstico anatomopatológico de carcinoma neuroendocrino en sus variantes pura y mixta. Se analizó edad, estadio clínico, antígeno prostático específico, estudios de gabinete, tratamiento y sobrevida. Resultados: Se incluyeron 10 casos con edad media de 66.5 años; los síntomas al momento del diagnóstico estaban asociados a invasión metastásica a distancia, siendo el principal el dolor óseo. Se identificó un tacto sospechoso en todos los pacientes y solo en tres (30 %) el antígeno prostático específico fue sospechoso de cáncer. Los estudios de extensión determinaron actividad metastásica ósea, locorregional, pulmonar y hepática. En seis (60 %) se documentó la variante mixta (adenocarcinoma acinar más carcinoma neuroendocrino), con una sobrevida promedio de 11.6 meses, y en cuatro (40 %) se registró carcinoma neuroendocrino puro, con una sobrevida promedio de siete meses. Conclusiones: El carcinoma neuroendocrino de próstata es infrecuente, agresivo y un ejemplo de neoplasia prostática que no expresa el antígeno prostático específico, con mala respuesta al bloqueo androgénico total en etapa avanzada.

BACKGROUND: Prostatic neuroendocrine carcinomas comprise <1% of all prostate neoplasms, and approximately 200 cases have been reported in the literature. We undertook this study to describe the experience in the management of prostatic neuroendocrine carcinoma with androgen-deprivation therapy (ADT). METHODS: We designed a retrospective, descriptive and observational study. In patients with suspicion of prostate cancer, transrectal ultrasonography-guided biopsy (TRUS) or transurethral resection of prostate (TURP) was carried out during the period from January 2000 to December 2007. Patients were selected by anatomopathological diagnostic study of neuroendocrine carcinoma including pure and mixed variants. Characteristics analyzed were age, clinical stage, prostate-specific antigen (PSA), imaging studies, treatment and survival. RESULTS: Ten cases were included with a median age of 66.5 years. Symptoms at diagnosis were associated with metastasis to other organs, one with bone metastasis, and presenting pain in 100% of the cases. A suspicious rectal digital examination was detected in 100% of the patients. In three (30%) patients, PSA was suspicious for prostate cancer. The extension studies showed bone, locoregional, lung and hepatic metastases. In six (60%) patients mixed variant was documented (acinar adenocarcinoma and neuroendocrine carcinoma) with a median survival of 11.6 months. In four patients (40%), pure neuroendocrine carcinoma was documented with a median survival of 7 months. CONCLUSIONS: Prostatic neuroendocrine carcinoma is uncommon, aggressive and represents a prostatic neoplasia without PSA expression. In advanced disease, very low response is reached with ADT.

Clinicopathologic Characteristics of Colorectal Neuroendocrine Tumor / 대한소화기학회지

BACKGROUND/AIMS: Colorectal neuroendocrine carcinoma is a rare neoplasm exhibiting fulminant progression and having poor prognosis. The purpose of this study is to verify the clinicopathologic characteristics of colorectal neuroendocrine carcinoma. METHODS: From June 1997 to December 2004 at Asan Medical Center, ten patients were originally identified as colorectal neuroendocrine carcinoma on the basis of H&E and immunohistochemical staining (IHC). Carcinoid tumors were excluded in this study. Medical records of thirteen patients were reviewed retrospectively. RESULTS: Ten patients (0.2%) with colorectal neuroendocrine tumors were identified from 4,512 patients with colorectal cancer; ten neuroendocrine carcinomas and three adenocarcinomas with neuroendocrine differentiation. Their median age was 60 (41-83) years. The subjects consisted of six males and seven females. Nine tumors were located in the rectum, two in the sigmoid, and each one in the transverse colon and cecum, respectively. Nine of ten neuroendocrine carcinomas expressed synaptophysin, but chromogranin A were expressed in four. All patients were advanced at the time of diagnosis, with AJCC TNM staging: stage IIIB (n=2), stage IIIC (n=3), and stage IV (n=8). The median survival for ten neuroendocrine carcinomas and three adenocarcinomas with neuroendocrine differentiation were 16.4 months and 30 months, respectively. Five patients who received chemotherapy showed median survival of 32 months (stage III) and 17.5 months (stage IV), whereas other five patients without chemotherapy died with a median survival of 6.2 months. CONCLUSIONS: Colorectal neuroendocrine tumors are extremely rare showing aggressive behavior biologically, i.e fulminant early distant metastasis. Nevertheless, improved survival may be achieved by aggressive multimodality therapy.