Clinicopathologic and Molecular Features of Mixed Neuroendocrine Non-Neuroendocrine Neoplasms of the Gallbladder

Alawad, Mouyed; Gupta, Raavi; Haseeb, Muhammad; Brunicardi, F. Charles

doi:10.14740/gr1323

Cited by 7 publications

(13 citation statements)

References 33 publications

(19 reference statements)

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“… 1 Mitotic rates arc expressed as number of mitoses/2 mm 2 as determined by counting in 50 fields of 0.2 mm 2 (in a total area of 10 mm 2 ); The Ki-67 proliferation index is determined by counting at least 500 cells in regions of highest labeling (hot-spots) which arc identified at scanning magnification; The Grade is based on whichever of the two proliferation indexes place the neoplasm in the higher grade category[ 6 ]. 2 NEC including {NEC, small-cell lype [SCNEC; NEC; large cell typc (LCNEC)]}; Mixed NENs including [mixed neuroendorine-non-neuroendorine neoplasms (MiNENs)]; Mixed adenoneuroendocrine carcinomas (MANECs).…”

Section: Resultsmentioning

confidence: 99%

Gallbladder neuroendocrine carcinoma diagnosis, treatment and prognosis based on the SEER database: A literature review

Cai¹,

Wu²

2022

WJCC

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BACKGROUND Gallbladder neuroendocrine carcinoma (GB-NEC) has a low incidence rate; therefore, its clinical characteristics, diagnosis, treatment and prognosis are not well explored. AIM To review recent research and analyze corresponding data in the Surveillance Epidemiology and End Results (SEER) database. METHODS Data of GB-NEC ( n = 287) and gallbladder adenocarcinoma (GB-ADC) ( n = 19 484) patients from 1975 to 2016 were extracted from the SEER database. Survival analysis was performed using Kaplan–Meier and Cox proportional hazards regression. P < 0.05 was considered statistically significant. We also reviewed 108 studies retrieved from PubMed and Reference Citation Analysis ( ). The keywords used for the search were: "(Carcinoma, Neuroendocrine) AND (Gallbladder Neoplasms)". RESULTS The GB-NEC incidence rate was 1.6% (of all gallbladder carcinomas), male to female ratio was 1:2 and the median survival time was 7 mo. The 1-, 2-, 3- and 5-year overall survival (OS) was 36.6%, 17.8%, 13.2% and 7.3% respectively. Serum chromogranin A levels may be a specific tumor marker for the diagnosis of GB-NEC. Elevated carcinoembryonic antigen, carbohydrate antigen (CA)-19-9 and CA-125 levels were associated with poor prognosis. Age [hazard ratio (HR) = 1.027, 95% confidence interval (CI): 1.006–1.047, P = 0.01] and liver metastasis (HR = 3.055, 95% CI: 1.839–5.075, P < 0.001) are independent prognostic risk factors for OS. Patients with advanced GB-NEC treated with surgical resection combined with radiotherapy and/or chemotherapy may have a better prognosis than those treated with surgical resection alone. There was no significant difference in OS between GB-NEC and GB-ADC. CONCLUSION The clinical manifestations and prognosis of GB-NEC are similar to GB-ADC, but the treatment is completely different. Early diagnosis and treatment are the top priorities.

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Section: Resultsmentioning

confidence: 99%

Gallbladder neuroendocrine carcinoma diagnosis, treatment and prognosis based on the SEER database: A literature review

Cai¹,

Wu²

2022

WJCC

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“…[ 33 ] However, patients with MiNEN of the GB lack early symptoms but present early vascular invasion and distant metastasis. [ 7 , 8 ] Therefore, MiNEN of the GB is regarded as a disease with a poor prognosis. In the case presented here, IP chemotherapy led to a marked reduction in both liver tumor and metastatic lymph node sizes, enabling the surgical treatment of this patient.…”

Section: Discussionmentioning

confidence: 99%

“…MiNENs have been reported at various sites of the gastrointestinal tract, [ 6 ] but MiNEN of the GB is rare. [ 7 , 8 ] In a recent study, MiNEN accounted for about 10% of GB cancers and about 2% of all hepatobiliary tract cancers. [ 9 ] Recently published data suggest that MiNEN of the GB is probably more frequent than expected, as more than one-third of diagnosed GB NECs are associated with non-neuroendocrine components.…”

Section: Introductionmentioning

confidence: 99%

Mixed neuroendocrine non-neuroendocrine neoplasm of the gallbladder complicated by a pancreaticobiliary maljunction of a non-dilated biliary duct

et al. 2021

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Rationale: Mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN) is a rare tumor. MiNEN of the gallbladder (GB) with pancreaticobiliary maljunction (PMJ) is extremely rare. The origin of MiNEN of the GB remains unknown; the biliary tract normally lacks neuroendocrine cells. MiNEN of the GB has a poor prognosis; because of its rarity, no treatment or management guidelines have been established yet. Patient concerns: A 47-year-old male presenting with right hypochondrial pain and malaise for 3 months was referred to our hospital for further management. Diagnosis: The neuron-specific enolase level was increased. Contrast-enhanced computed tomography revealed a mass of 70 mm in size with unclear boundaries in the liver. The GB was surrounded by this mass, narrowing the lumen of the GB. Many swollen lymph nodes were observed in the hepatoduodenal ligament. Endoscopic retrograde cholangiopancreatography revealed a PMJ with a non-dilated biliary duct. A percutaneous biopsy was performed on the liver mass, and the pathological findings were neuroendocrine carcinoma (NEC) (small cell type). We diagnosed a NEC of the GB, T3N1M0, stage IIIB (Union for International Cancer Control, 7th edition). Interventions: Because of advanced lymph node metastasis, we considered this tumor difficult to cure solely by surgical intervention. After initial chemotherapy consisting of cisplatin and irinotecan, a marked reduction in both tumor and lymph node sizes enabled conversion surgery. The pathological diagnosis of the resected tumor was MiNEN consisting of NEC and adenocarcinoma. The primary lesion was the adenocarcinoma occupying the luminal side of the GB. As a postsurgical treatment, the patient received additional irradiation therapy to the common hepatic duct and liver stump because of positive surgical margins. Outcomes: At 13 months postoperatively, computed tomography findings revealed the appearance of a hypervascular liver tumor, and laboratory data showed increased serum neuron-specific enolase levels. Chemotherapy was unsuccessful, leading to the death of the patient 36 months from the date of diagnosis. Lessons: There are several reports on the development of MiNEN of the GB. In our case, a PMJ-related adenocarcinoma of the GB transdifferentiated into NEC. Further accumulation of cases is necessary to establish a treatment strategy for MiNEN of the GB.

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“…The close relationships between MiNENs and inflammatory diseases in these locations suggest that inflammation plays a role in pathogenesis. Recent findings indicate that the NEC component of the tumor is composed of large cell NECs in a great majority of cases (59%), and NECs are incidentally discovered during imaging studies without any specific clinical findings[ 112 ]. In parallel, specific findings that differ from the findings for adenocarcinomas on macroscopic examination have not been observed.…”

Section: Organ-specific Clinicopathological Findingsmentioning

confidence: 99%

“…Therefore, the rarity of distant metastases in these tumors does not exclude the possibility that half of them metastasize to neighboring organs (liver, peritoneum, lymph nodes) at the time of diagnosis. On histopathologic evaluation, the nonneuroendocrine component often consists of adenocarcinoma and rarely consists of squamous cell carcinoma or carcinoma with sarcomatous or osteosarcomatous differentiation[ 112 , 113 ]. Few cases with intracystic papillary neoplasms (IPNs) have also been reported[ 16 ].…”

Section: Organ-specific Clinicopathological Findingsmentioning

confidence: 99%

Mixed neuroendocrine–nonneuroendocrine neoplasms of the gastrointestinal system: An update

Elpek¹

2022

WJG

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Mixed neuroendocrine-nonneuroendocrine neoplasms (MiNENs) of the digestive tract are a rare heterogeneous group of tumors that present many challenges in terms of diagnosis and treatment. Over the years, the diagnostic criteria, classification, and clinical behavior of these tumors have been the subjects of ongoing debate, and the various changes in their nomenclature have strengthened the challenges associated with MiNENs. This review is performed to provide an understanding of the key factors involved in the evolution of the designation of these tumors as MiNEN, highlight the current diagnostic criteria, summarize the latest data on pathogenesis and provide information on available treatments. Moreover, this work seeks to increase the awareness about these rare neoplasms by presenting the clinicopathological features and prognostic factors that play important roles in their behavior and discussing their different regions of origin in the gastrointestinal system (GIS). Currently, the MiNEN category also includes tumors in the GIS with a nonneuroendocrine component and epithelial tumors other than adenocarcinoma, depending on the organ of origin. Diagnosis is based on the presence of both morphological components in more than 30% of the tumor. However, this value needs to be reconfirmed with further studies and may be a limiting factor in the diagnosis of MiNEN by biopsy. Furthermore, available clinicopathological data suggest that the inclusion of amphicrine tumors in the definition of MiNEN is not supportive and warrants further investigation. The diagnosis of these tumors is not solely based on immunohistochemical findings. They are not hybrid tumors and both components can act independently; thus, careful grading of each component separately is required. In addition to parameters such as the metastatic state of the tumor at the time of diagnosis and the feasibility of surgical resection, the aggressive potential of both components has paramount importance in the choice of treatment. Regardless of the organ of origin within the GIS, almost MiNENs are tumors with poor prognosis and are frequently encountered in the elderly and men. They are most frequently reported in the colorectum, where data from molecular studies indicate a monoclonal origin; however, further studies are required to provide additional support for this origin.

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Clinicopathologic and Molecular Features of Mixed Neuroendocrine Non-Neuroendocrine Neoplasms of the Gallbladder

Cited by 7 publications

References 33 publications

Gallbladder neuroendocrine carcinoma diagnosis, treatment and prognosis based on the SEER database: A literature review

Gallbladder neuroendocrine carcinoma diagnosis, treatment and prognosis based on the SEER database: A literature review

Mixed neuroendocrine non-neuroendocrine neoplasm of the gallbladder complicated by a pancreaticobiliary maljunction of a non-dilated biliary duct

Mixed neuroendocrine–nonneuroendocrine neoplasms of the gastrointestinal system: An update

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