A Rare Case of Mixed Adenoneuroendocrine Carcinoma (MANEC) of the Gastroesophageal Junction with HER2/neu Overexpression and Distinct Orbital and Optic Nerve Toxicity after Intravenous Administration of Cisplatin

Abstract

Background: Mixed adenoneuroendocrine carcinomas (MANECs) are rare malignancies with both neuroendocrine and non-neuroendocrine components. To date, the prognosis of gastroenteropancreatic MANECs remains dismal, and treatment options are mainly based on guidelines for the treatment of pure neuroendocrine carcinomas or small cell lung cancer. Established first-line therapy in the metastatic situation is cisplatin and etoposide. Platinum derivatives are known to cause a variety of side effects also involving the visual system. Severe orbital and optic nerve toxicities have been described mainly after intracarotid infusion of cisplatin. Case Report: Herein we report a rare case of a 60-year-old male patient suffering from MANEC of the gastroesophageal junction with HER2/neu overexpression who developed severe orbital and ocular neurotoxicity (grade 3 according to CTCAE v4.03) after intravenous cisplatin. Conclusion: We discuss diagnostic approaches and differential diagnoses in this clinical situation. Before starting treatment with intravenous and topical steroids, it is crucial to rule out meningeal and cerebral spread as well as paraneoplastic and endocrine syndromes.

Mixed Neuroendocrine Non-Neuroendocrine Neoplasms: A Systematic Review of a Controversial and Underestimated Diagnosis

“…Among 69 studies (n = 667) reporting the grade of differentiation of the neuroendocrine component [11][12][13][14][15][16][17][18][19][21][22][23][24][25][26][27][28][29][54][55][56][57][58][59][60][61][62]68,71,[73][74][75]79,80,82,[84][85][86][87]89,[91][92][93]96,97,100,101], a large proportion of MiNENs (92.5%; n = 617) had a grade 3 neuroendocrine component, whereas 4.3% (n = 29) and 3.1% (n = 21) had a grade 1 and a grade 2 neuroendocrine component, respectively. Among MiNENs with a grade 3 neuroendocrine component, the morphological subtype (large cell or small cell) was reported in 25 studies (n = 241) [11,…”

“…The histology of the non-neuroendocrine component was reported in 74 studies (n = 606) [11][12][13]64,65,68,[72][73][74][75][79][80][81][82][84][85][86][87]89,[91][92][93][95][96][97]101], and was consistent with an adenocarcinoma in 92.2% of cases (n = 559) (acinar cell carcinoma in 7.6% (n = 46)), an adenoma in 4.5% (n = 27), a squamous cell carcinoma in 2.5% (n = 15), a hepatocellular carcinoma in < 1% (n = 1), and a mixture of an adenocarcinoma and a squamous cell carcinoma in < 1% (n = 4). The grade of differentiation of the non-neuroendocrine component was specified in 38 studies (n = 124), and was well differentiated in 24.2% (n = 30), moderately differentiated in 35.5% (n = 44), and poorly differentiated in 39.5% (n = 49).…”

“…Interestingly, in 43 studies (n = 61) where more than one diagnostic sample was available [11,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]30,[32][33][34][36][37][38][39][41][42][43][44][45][46][47]49,50,53,55,[59][60][61][62]64,65,96], the initial diagnosis from the first sample collected (either cytological or histological) was in keeping with MiNEN or suspicion of MiNEN in 36.1% (n = 22) of cases, adenocarcinoma in 36.1% (n = 22), poorly differentiated neuroendocrine carcinoma in 21.3% (n = 13), and well differentiated neuroendocrine tumour in 6.6% (n = 4).…”

“…The histology of synchronous or metachronous distant metastases was reported in 14 studies (N = 51) [11,17,22,31,50,57,58,[62][63][64]85,86,92,96], and was consistent with a single or predominant poorly differentiated neuroendocrine component in 60.8% (n = 31) of cases, with a mixture of a neuroendocrine carcinoma and an adenocarcinoma in 33.3% (n = 17), and a single or predominant adenocarcinoma component in 5.9% (n = 3).…”

A Patient with an Ileocecal MiNEN and a Synchronous Squamous Non-Small-Cell Lung Cancer: Case Report and Review of the Literature

“…This data correlates to that of scientific reports showing a prevalence of 0.048% for NEN in the USA and recently increasing incidences ranging from 2.5-5/100,000 to 8.4/100,000 (in the USA and Europe, respectively), mostly thanks to earlier detection and increased use of endoscopy and other diagnostic techniques over time [11,13]. MiNENs, on the other hand, are even rarest entities, representing 1-1.5% of all gastroenteropancreatic neoplasms [14], data that however highly surpasses that of ours. Interestingly, none of the 6 MiNEN/MANEC cases in our center was recorded before 2018.…”