Rectal mixed adenoneuroendocrine carcinoma: Case report.

RATIONALE: Colorectal mixed neuroendocrine-nonneuroendocrine neoplasms constitute a rare group of gastrointestinal tumors composed by both neuroendocrine and nonneuroendocrine components. Nondiagnostic macroscopic features, specific histological features, and poor awareness of the disease are responsible for the underestimated incidence and conflicting data available. Due to lack of randomized clinical trials and validated clinical guidelines, diagnostic and therapeutic approach are based on the standard of care for pure colorectal neuroendocrine carcinomas or adenocarcinomas. PATIENT CONCERNS: A 76-year-old caucasian male, without relevant medical or familial history, presented a positive faecal occult blood test during colorectal cancer screening. DIAGNOSIS: Total colonoscopy identified a rectal lesion with biopsy showing a moderate rectal adenocarcinoma staged as cT2N0M0. INTERVENTIONS: Anterior resection of the rectum with right ileostomy followed by local radiotherapy with radio-sensitising chemotherapy and adjuvant chemotherapy with capecitabine 1000 mg bid plus oxaliplatin 130 mg/m2. Due to chronic nodular pulmonary aspergillosis and chemotherapy induced immunosuppression patient was on 400 mg/daily of oral voriconazole. OUTCOMES: Overall survival of 15 months after progression under first line treatment and under palliative chemotherapy with platinum plus etoposide regimen. LESSONS: The reported case illustrates the challenge associated to the management of mixed neuroendocrine-nonneuroendocrine carcinomas due to lack of validated guidelines and scientific evidence. From diagnosis and staging to treatment, all steps must be tailored to individual clinical and histological features.

Survival and prognostic factors of salivary gland malignant mixed tumor-not otherwise specified: A population-based analysis.

OBJECTIVE: Malignant mixed tumors of the salivary gland are a group of neoplasms comprised of carcinoma-ex-pleomorphic adenoma, carcinosarcoma, and metastasizing pleomorphic adenoma. An alternative classification, malignant mixed tumor-not otherwise (MMT-NOS), is a diagnosis of exclusion for neoplasms that do not fit the previous histologically profiled subtypes. The objective was to provide a comprehensive assessment of MMT-NOS and determine prognostic factors. METHODS: This retrospective cohort study queried the Surveillance, Epidemiology, and End Results database for patient and tumor characteristics of US patients with MMT-NOS of the major salivary glands from 1973 to 2016. Kaplan-Meier and Cox regression analysis were performed to determine 5-year survival and prognostic factors. RESULTS: 434 patients were identified with a mean age at diagnosis of 61.5 years. The majority of neoplasms were high grade and stage (70.8% grade III/IV; 63.8% stage III/IV). Extraparenchymal extension (40.6%) and lymph node involvement (28.5%) were common; distant metastases (2.4%) were rare. Treatment included surgery (93.0%), radiation (51.6%), and chemotherapy (10.4%). Facial nerve sacrifice was common (50.8%). Median survival was 66.5 months. 5-year overall and disease-specific survival were 65.7% and 83.0%, respectively. In multivariate analysis, nodal involvement (HR 7.0; P < 0.001), surgery-radiation-chemotherapy (HR 6.1; P = 0.02), extraparenchymal extension (HR 2.50; P = 0.04), and tumor size >4 cm (HR 1.3; P = 0.03) were prognostic factors. CONCLUSION: Despite high stage and grade at diagnosis, MMT-NOS portends a good 5-year prognosis and low rate of distant metastasis. Prognostic factors were nodal involvement, tumor size, and extraparenchymal extension.

The clinical profiles, management, and prognostic factors of biliary mixed neuroendocrine nonneuroendocrine neoplasms: A systematic review of the literature.

BACKGROUND: Mixed neuroendocrine nonneuroendocrine neoplasms (MiNENs) originating from the biliary system (gallbladder, biliary tract, or ampulla of Vater) are extremely rare and have not been discussed in detail or systematically. We aimed to present the demographics, clinicopathological characteristics, management, and prognostic factors of biliary MiNENs. METHODS: A systematic search of electronic biomedical databases (Web of Science, PUBMED, and Embase) was performed to identify eligible studies. Survival was analyzed with the Kaplan-Meier method. Log-rank tests were used to evaluate the differences between groups, and the effects of various clinical and histopathological features on prognosis were analyzed by univariate and multivariate Cox regression. RESULTS: Fifty-three publications (patients, n = 67) were included. The median overall survival time was 21.0 months. Fifty-one patients (76.1%) underwent radical surgery and median survival for 41 months (P < .001). Twenty-two patients who received adjuvant radiochemotherapy treatment after radical surgery had a median survival for 43 months (P = .076). Radical resection (P < .001), Ki-67 index (P = .011), tumor stage (P < .001), neuroendocrine (NEC) grade (P = .011), and non-NEC grade (P = .017) were independent statistically significant prognostic factors according to univariate analysis; radical resection (P = .010) and small morphological subtype (P = .036) were independent statistically significant prognostic factors associated with higher overall survival according to multivariate analysis, and radical resection (P = .005) and age < 65 years (P = .026) were associated with higher recurrence free survival time. CONCLUSION: Radical resection is essential for long-term survival. Aggressive multimodality therapy with adjuvant radiochemotherapy and biotherapy may improve survival of biliary MiNENs. Further randomized controlled trials are needed to determine the standard treatment.

Tumor neuroendocrino de la vesícula biliar / Neuroendocrine tumour of the gallbladder

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Adult-Onset Mixed Germ Cell Tumor Composed Mainly of Yolk Sac Tumor Around the Pineal Gland: A Case Report and Review of the Literature.

BACKGROUND: Mixed germ cell tumors (MGCTs) usually occur in children. In the present report, we discuss an extremely rare case of adult-onset MGCT composed mainly of yolk sac tumor (YST) around the pineal gland. CASE DESCRIPTION: A 54-year-old Japanese man presented with disturbance of consciousness, Parinaud's syndrome, and gait disturbance. Magnetic resonance imaging revealed a pineal mass lesion, and subtotal resection of the tumor was achieved. The histologic diagnosis was MGCT, consisting mainly of YST. Although he underwent 5 courses of chemotherapy and craniospinal irradiation after surgery, tumor dissemination could not be controlled, and he died 10 months postoperatively. CONCLUSION: The present case highlights the need for clinicians to include YST in the differential diagnosis of acute progressive lesions around the pineal region, even in adult patients.

Mixed neuroendocrine-non-neuroendocrine carcinoma of gallbladder: case report.

BACKGROUND: Mixed neuroendocrine-non-neuroendocrine tumors (MINEN) of the gallbladder are extremely rare; indeed, the English expert literature reports a mere handful of case reports and case series on this topic. According to the WHO classification of 2010, MINEN are considered to be tumors consisting of two major components, neuroendocrine and non-neuroendocrine, each of which hosts at least 30% of the total cellular population. To date, the etiology and pathogenesis of MINEN have not been precisely determined and the non-specific symptoms generally result in late diagnosis (mainly in the terminal stages of the condition) and contribute to the generally poor prognosis. As far as the management of the disease is concerned, radical surgery plays a crucial role; however, the significance of surgical debulking and biological therapy applying somatostatin analogues has not yet been determined. CASE PRESENTATION: A 56-year-old female was referred to our department for a rapidly progressing tumor in the subhepatic area along with the infiltration of S5 and S6 liver segments. With regard to preoperative findings, the tumor appeared as operable, although, during the surgery, an extensive involvement of the hepatoduodenal ligament by the tumor through the lymph nodes was revealed. Due to acute perioperative bleeding from the necrotic tumor, we decided to perform modified resection. Histologically, the tumor was confirmed as MINEN of gallbladder, where the neuroendocrine component was dominant over the non-neuroendocrine component. Six weeks after the discharge, the patient underwent a follow-up CT revealing large recurrence of the disease. Thereafter, the patient was started on systemic therapy with etoposide and carboplatin in combination with somatostatin analogues. Thirteen months after the surgery, the patient is in good clinical condition, and while a recently performed PET/MRI scan revealed a hepatic lesion and hilar lymphadenopathy in full regression, there was a spread of small peritoneal and pleural metastases. The patient remains in the follow-up care. CONCLUSIONS: The occurrence of mixed neuroendocrine-non-neuroendocrine neoplasms is extremely rare. Radical surgery remains the only potentially effective approach to the cure of this disease. The role of biological therapy and debulking in the management of the disease has not yet been precisely defined. In our experience, both of these methods have the potential to positively influence overall survival rates and the postoperational quality of life of patients.

[Histological and molecular classification of endometrial carcinoma and therapeutical implications]. / Classification histologique et moléculaire des cancers de l'endomètre et leurs implications dans la thérapeutique.

Endometrial cancer is the fourth cause of cancer in women in France and is the second most common cancer of the gynecologic cancer after breast cancer with 7275 new cases in 2012. The incidence of this neoplasm tends to increase with population aging, diabetes and obesity's augmentation. In rare cases, a hereditary factor has been described: Lynch's syndrome. The therapeutic management of the patient depends on the endometrial biopsy which specifies the histological type and the histo-prognostic grade as well as the MRI which allow the tumor staging. Within the last decade, improvement in technologies such as genomic, transcriptomic and histological analyses, allowed the establishment of new and finer classifications of endometrial carcinomas. The latest classification proposed by The Cancer Genomic Atlas (TCGA), has been made routinely applicable through the international consortium TransPORTEC. It consists of 4 groups listed from good to poor prognosis: (1) ultra-mutated "POLE"; (2) hyper-mutated "MSI"; (3) low copy number "NSMP" and (4) high number of copies "TP53 mutated" (serous-like). This integrated characterization combined with mutational data opens new opportunities for therapeutic strategies.

Ampullary Mixed Adenoneuroendocrine Carcinoma: Surprise Histology, Familiar Management.

INTRODUCTION: Mixed adenoneuroendocrine carcinoma (MANEC) has recently been defined by the World Health Organization in 2010. These are rare tumors and MANECs of ampullary region are even rarer. Only 19 cases have been reported in literature. We present 3 cases; the largest series, second case of amphicrine tumor and first case associated with chronic pancreatitis. METHODS: Retrospective review of 3 patients who were diagnosed to have ampullary MANEC. RESULTS: All 3 patients were diagnosed preoperatively as neuroendocrine carcinoma and underwent margin negative pancreaticoduodenectomy. The histopathology revealed MANECs of small cell, mixed type in 2 patients and large cell, amphicrine type in 1 patient. The neuroendocrine component was grade 3 in all, the tumor was T3 in 2 and T2 in 1 and all had nodal metastases. Two patients received adjuvant chemotherapy and 2 of them had recurrence at 13 and 16 months. The median survival was 15 months. CONCLUSION: Ampullary MANECs are rare tumors. They are diagnosed on histopathologic examination of the resected specimen. Clinical presentation, management, and prognosis is similar to ampullary adenocarcinoma in literature.

Mixed adenoneuroendocrine carcinoma of the gastric stump following Billroth II gastrectomy: case report and review of the literature / Adenocarcinoma neuroendócrino misto do coto gástrico após gastrectomia à Billroth II: relato de caso e revisão de literatura

CONTEXT: Gastric stump cancer after gastric resection is a well-known disease. It may be a newly developed cancer after resection due to benign disease, or recurrent or residual disease after oncological surgery. The predominant histological type is usually adenocarcinoma. This study aimed to report on a rare occurrence of a mixed adenoneuroendocrine carcinoma (MANEC) on the gastric stump. CASE REPORT: The case of an 83-year-old female who presented a locally aggressive gastric stump MANEC, 35 years after Billroth II gastrectomy to treat a peptic ulcer, is reported. The patient underwent resection and adjuvant therapy. She has been followed up for one year without signs of recurrence. CONCLUSION: MANEC is a rare type of gastrointestinal neoplasm. The classification, histopathology, clinical features, treatment issues and prognosis are discussed along with a brief review of the literature.

CONTEXTO: O câncer de coto gástrico após gastrectomia é uma condição extensamente documentada. Pode se tratar de doença desenvolvida após a ressecção por doença benigna, ou ainda doença recorrente ou residual após cirurgia oncológica. Geralmente, o tipo histológico predominante é o adenocarcinoma. Este estudo tem como propósito relatar a rara ocorrência de um adenocarcinoma neuroendócrino misto (MANEC) no coto gástrico. RELATO DE CASO: É relatado o caso de uma mulher de 83 anos que apresentou um MANEC localmente agressivo 35 anos após uma gastrectomia à Billroth II devido a úlcera péptica. Foi submetida a ressecção e terapia adjuvante e foi seguida por 12 meses sem sinais de recorrência. CONCLUSÃO: Os MANECs constituem raro tipo de neoplasia gastrointestinal. Sua classificação, histopatologia, aspectos clínicos, tratamento e prognóstico são discutidos junto com uma breve revisão de literatura.

Mixed adenoneuroendocrine carcinoma of the gastric stump following Billroth II gastrectomy: case report and review of the literature.

CONTEXT: Gastric stump cancer after gastric resection is a well-known disease. It may be a newly developed cancer after resection due to benign disease, or recurrent or residual disease after oncological surgery. The predominant histological type is usually adenocarcinoma. This study aimed to report on a rare occurrence of a mixed adenoneuroendocrine carcinoma (MANEC) on the gastric stump. CASE REPORT: The case of an 83-year-old female who presented a locally aggressive gastric stump MANEC, 35 years after Billroth II gastrectomy to treat a peptic ulcer, is reported. The patient underwent resection and adjuvant therapy. She has been followed up for one year without signs of recurrence. CONCLUSION: MANEC is a rare type of gastrointestinal neoplasm. The classification, histopathology, clinical features, treatment issues and prognosis are discussed along with a brief review of the literature.

Endocrine cell carcinomas of the colon and rectum: a clinicopathological evaluation.

PURPOSE: Endocrine cell carcinoma, according to the Japanese classification criteria for colorectal cancer, corresponds to neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma (MANEC), as defined in the 2010 World Health Organization (WHO) classification. We retrospectively reviewed the clinical features of patients with these tumors diagnosed and treated at our institution. METHODS: The clinicopathological features of endocrine cell carcinomas of the colon and rectum diagnosed by neuroendocrine markers from January 2000 to December 2012 were retrospectively evaluated in 12 patients. RESULTS: Surgical specimens were obtained from eight of the 12 patients. MANEC was diagnosed in six patients and NEC in one. One tumor was unclassifiable. The tumors were not resected in four patients, and all died within 3 months. Of the eight patients who underwent resection, four received an R0 resection, two of whom underwent adjuvant chemotherapy and survived more than 5 years. One patient who underwent an R2 resection and continuous chemotherapy survived for 53 months. One patient with NEC underwent surgery and radiotherapy, and died 17 months later. CONCLUSION: Most endocrine cell carcinomas of the colon and rectum reviewed were MANECs. Though their prognosis was generally poor, chemotherapy may be effective in some patients.

Zoledronic acid-associated symmetrical drug-related intertriginous and flexural exanthema (SDRIFE): report of baboon syndrome in a woman with recurrent metastatic breast cancer after receiving zoledronic acid.

BACKGROUND: Baboon syndrome is a distinctive skin reaction in which the patient typically develops erythematous buttocks that appear similar to those of a baboon. The non-contact allergenic variant of baboon syndrome is also referred to as symmetrical drug-related intertriginous and flexural exanthema (SDRIFE). Zoledronic acid is a bisphosphonate that is used in patients with metastatic cancer to prevent bone complications. PURPOSE: Zoledronic acid-associated baboon syndrome is described in a woman with recurrent metastatic breast cancer. METHODS: PubMed was used to search the following terms, separately and in combination: baboon syndrome, breast cancer, symmetrical drug-related intertriginous and flexural exanthema, and zoledronic acid. All papers were reviewed and relevant manuscripts, along with their reference citations, were evaluated. RESULTS: Zoledronic acid has infrequently been associated with mucocutaneous adverse reactions. However, baboon syndrome has not previously been observed in patients receiving zoledronic acid. The reported woman developed baboon syndrome after her initial exposure to zoledronic acid. CONCLUSIONS: Non-contact allergenic drug-induced baboon syndrome has most commonly been associated with antibiotics such as beta-lactams and penicillins. Zoledronic acid-associated baboon syndrome has not previously been observed in cancer patients. Baboon syndrome (SDRIFE variant) was observed in a woman with recurrent metastatic breast cancer after her first exposure to zoledronic acid. In summary, SDRIFE can occur in oncology patients receiving zoledronic acid and zoledronic acid should be added to the list of medications associated with the potential to cause non-contact allergenic drug-induced baboon syndrome.

[Clinicopathologic features of combined hepatic carcinoma].

OBJECTIVE: To investigate clinicopathological features of combined hepatocellular-cholangiocarcinoma (C-HCC-CC) with neuroendocrine carcinoma (NEC) differentiation and to review the literature. METHODS: The clinical data, histological manifestations and immunohistochemical staining results of two cases of C-HCC-CC were analyzed along with a review of the current literature. RESULTS: Both patients were male with an average age of 57.5 years. Both patients were positive for hepatitis B virus antigen. The tumors of both cases demonstrated the following 3 unequivocal mixed elements: (1) polygonal epithelial tumor cells growing in nests or trabeculae with positive staining for Hepatocyte and AFP, diagnostic of hepatocellular carcinoma (HCC). Cytoplasmic bile production was present in the tumor cells in one case; (2) elliptic or short spindle-shape small blue tumor cells growing in nests or organoid pattern with Syn/CgA/CD56 positivity confirming the presence of neuroendocrine carcinoma (NEC) component; (3) oval tumor cells growing in nests or glandular forms with positivity of CK19 and CK7 confirming differentiation of cholangiocarcinoma (CC). In both cases, the tumors contained at least 20% of each of HCC, NEC and CC components. CONCLUSION: C-HCC-CC with NEC is a rare form of primary malignancy of the liver with a poor prognosis.

Long-term treatment outcome of minor salivary gland carcinoma of the hard palate.

Minor salivary gland carcinoma of the hard palate is rare, and its long-term survival rate is high, making it difficult to evaluate the prognostic factors and the efficacy of treatment. This study was designed to evaluate the treatment outcome of minor salivary gland carcinoma of the hard palate. 103 cases of minor salivary gland carcinoma of the hard palate treated with surgery alone or underwent surgery combined with post-operative radiotherapy hospitalized in Cancer Center, Sun Yet-Sen University, from 1968 to 2008 were reviewed retrospectively. The most common histologic types were adenoid cystic carcinoma in 48 patients(46.6%), mucoepidermoid carcinoma in 37(35.92%), malignant mixed tumor in 15(14.56%), and acinic cell carcinoma in 3(2.91%). The median follow-up time was 74.83 months (range 0.9-356.57 months). Overall outcomes at 5 and 10 years were overall survival (OS), 77.9% and 65.7%; recurrence-free survival (RFS), 64.4% and 53.2%; and disease specific survival (DSS), 77.9% and 67.7%, respectively. There was no significant difference in overall survival (P=0.52), recurrence-free survival (P=0.762) and disease specific survival (P=0.449) between patients who underwent surgery alone and those who underwent surgery plus post-operative radiotherapy. Surgery has been accepted as the primary treatment for minor salivary gland carcinoma of hard palate. Sufficient surgical excision with adequate margins is essential for a favorable outcome. We advocate using radiotherapy in the post-operative context for patients with poorly differentiated, cervical lymph node metastasis, positive or close margins, and large primary lesions.

The prognoses of metaplastic breast cancer patients compared to those of triple-negative breast cancer patients.

Metaplastic breast carcinoma (MBC) is a rare, heterogeneous breast cancer characterized by admixture of adenocarcinoma with metaplastic elements, low hormone receptor expression, and poor outcomes. The authors retrospectively reviewed the medical records of 47 MBC patients and 1,346 invasive ductal carcinoma (IDC) patients. Two hundred eighteen of the IDC patients were triple-negative (TN-IDC) for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 (ER-/PR-/HER2-). Patients were surgically treated at the Samsung Medical Center between 2005 and 2009. The MBC patients presented with a larger tumor size, lower lymph node involvement, higher histological and nuclear grades, higher triple negativity (ER-/PR-/HER2-) and higher p53, CK5/6, and EGFR expressions compared with those of the IDC group. However, there were no significant differences in clinicopathological characteristics between MBC and TN-IDC. During the follow-up period (median duration of 30.3 months, range 2.6-56.3 months), seven (14.9%) MBC patients, and 98 (7.1%) IDC patients had disease recurrence. The three-year disease-free survival (DFS) rate was 78.1% in the MBC group and 91.1% in IDC group (P < 0.001). The three-year DFS rate was not significantly different between the MBC and TN-IDC groups (78.1 vs. 84.9%, P = 0.114). However, in patients with lymph node metastasis who underwent adjuvant chemotherapy, the three-year DFS rate was 44.4% in the MBC group and 72.5% in the TN-IDC group (P = 0.025). The authors found that MBC had a poorer clinical outcome than did IDC. In breast cancer patients with nodal metastasis, MBC had a poorer prognosis than did TN-IDC, despite adjuvant chemotherapy.

Do clinical and immunohistochemical findings of pure mucinous breast carcinoma differ from mixed mucinous breast carcinoma?

Mucinous carcinoma of the breast is a relatively rare histologic type with two subtypes: pure and mixed. It has a favourable prognosis with a low risk of axillary metastases. The prognosis for pure mucinous carcinoma (PMC) was much better than for the mixed mucinous carcinoma (MMC). The aim of the study is to determine suitable candidates for breast or axillary conservation in mucinous carcinoma subtypes. The slides of 26 pure and 23 mixed mucinous carcinomas of the breast were evaluated. The clinical, pathological and immunohistochemical features between PMCs and MMCs were compared. MMC displayed greater metastatic potential (p < 0.05), p53 positivity (p < 0.05) and c-erbB-2 positivity (p <0.001) than PMCs. PMCs smaller than 2 cm had less metastatic capacity and extranodal invasion compared to MMCs smaller than 2 cm (p < 0.001 and p < 0.01, respectively). MMCs smaller than 2 cm displayed weaker ER positivity but greater c-erbB-2 positivity than PMCs smaller than 2 cm (p < 0.01). In conclusion, MMC had worse prognostic factors than PMC with both types of mucinous carcinoma showing similar ER and PR positive status. Even if PMCs and especially smaller PMCs display more favourable prognostic features, including less axillary lymph node involvement, it is appropriate to use sentinel lymph node biopsy to make better axillary assessment.

Placental-site trophoblastic tumors: a case of resistant pulmonary metastasis.

Background A 52-year-old woman whose last known pregnancy was 12 years before presentation was diagnosed with mixed trophoblastic tumor that included placental-site trophoblastic tumor, epithelioid trophoblastic tumor, and focal choriocarcinoma. There was no clear evidence of metastatic disease on initial evaluation. Investigations Histopathology, laboratory tests, immunohistochemistry, chest X-ray, CT scan of the chest, abdomen, and pelvis, fine-needle aspiration biopsy, PET-CT scan.Diagnosis Metastatic chemoresistant placental-site trophoblastic tumor positive for EGFR, VEGF receptor, and platelet-derived growth factor receptor. Management Abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic radiation, etoposide, methotrexate, actinomycin D/cyclophosphamide and vincristine chemotherapy, left thoracotomy with wedge resection, taxol, etoposide, cisplatin therapy, right thoracotomy with wedge resection.

Aggressive mixed type endometrial carcinoma in a young woman with rapid progression and fatal outcome.

INTRODUCTION: Endometrial carcinoma in young ages is uncommon and tends to be a well differentiated endometrioid type and has an excellent prognosis. Nevertheless, in this report mixed type endometrial cancer including serous, clear cell and endometrioid components in a young patient with rapid progression and fatal outcome is presented. CASE: A 26-year-old virgin female was admitted with menometrohagia lasting for 9 months, leading to severe anemia. Transabdominal ultrasonography demonstrated 30 x 27 mm intramural mass consistent with leiomyoma in uterine corpus posterior. The patient did not permit any vaginal intervention including endometrial sampling, therefore laparotomy was decided. Mixed type endometrial carcinoma was diagnosed and she was treated with comprehensive surgery plus adjuvant chemotherapy. After 7 months of surgery she deceased. CONCLUSION: We suggest that persistent uterine bleeding associated with severe anemia should be evaluated for malignancy even in young women to avoid delay in diagnosis. Imaging studies especially magnetic resonance imaging may be helpful when endometrial sampling cannot be done.