Primary MiNEN of the urinary bladder: an hitherto undescribed entity composed of large cell neuroendocrine carcinoma and adenocarcinoma with a distinct clinical behavior

AbstractNeuroendocrine carcinomas (NECs) of the urinary bladder are very rare and can be observed in the context of mixed neuroendocrine/non-neuroendocrine neoplasms (MiNENs), most frequently in association with urothelial carcinoma. Small cell NECs are far more common than large cell NECs (LCNECs), which are exceedingly rare. We describe a primary MiNEN of the urinary bladder, composed of a LCNEC and of an adenocarcinoma, in which the neuroendocrine component reached complete pathological regression after neoadjuvant M-VAC chemotherapy, whereas the non-neuroendocrine component of the tumor progressed to metastatic disease. Compared to mixed neuroendocrine/non-neuroendocrine neoplasms described in the literature until now, this appears to be a unique case that expands the spectrum of neuroendocrine neoplasia of the urinary bladder.

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Neuroendocrine Carcinoma of the Uterine Cervix: A Clinicopathologic and Immunohistochemical Study with Focus on Novel Markers (Sst2–Sst5)

Cancers ◽

10.3390/cancers12051211 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1211

Author(s):

Frediano Inzani ◽

Angela Santoro ◽

Giuseppe Angelico ◽

Angela Feraco ◽

Saveria Spadola ◽

...

Keyword(s):

Differential Diagnosis ◽

Target Therapy ◽

Somatostatin Receptors ◽

Neuroendocrine Differentiation ◽

Large Cell ◽

Cell Types ◽

Somatostatin Analogues ◽

Small Cell ◽

Neuroendocrine Neoplasms ◽

Neuroendocrine Carcinomas

Background. Gynecological neuroendocrine neoplasms (NENs) are extremely rare, accounting for 1.2–2.4% of the NENs. The aim of this study was to test cervical NENs for novel markers of potential utility for differential diagnosis and target therapy. Methods. All cases of our center (n = 16) were retrieved and tested by immunohistochemistry (IHC) for 12 markers including markers of neuroendocrine differentiation (chromogranin A, synaptophysin, CD56), transcription factors (CDX2 and TTF1), proteins p40, p63, p16INK4a, and p53, somatostatin receptors subtypes (SST2-SST5) and the proliferation marker Ki67 (MIB1). Results. All cases were poorly differentiated neuroendocrine carcinomas (NECs), 10 small cell types (small cell–neuroendocrine carcinomas, SCNECs) and 6 large cell types (large cell–neuroendocrine carcinomas, LCNECs); in 3 cases a predominant associated adenocarcinoma component was observed. Neuroendocrine cancer cells expressed at least 2 of the 3 tested neuroendocrine markers; p16 was intensely expressed in 14 (87.5%) cases; SST5 in 11 (56.25%, score 2–3, in 9 cases); SST2 in 8 (50%, score 2–3 in 8), CDX2 in 8 (50%), TTF1 in 5 (31.25%), and p53 in 1 case (0.06%). P63 and p40 expressions were negative, with the exception of one case that showed moderate expression for p63. Conclusions. P40 is a more useful marker for the differential diagnosis compared to squamous cell carcinoma. Neither CDX2 nor TTF1 expression may help the differential diagnosis versus potential cervical metastasis. P16 expression may suggest a cervical origin of NEC; however, it must be always integrated by clinical and instrumental data. The expression of SST2 and SST5 could support a role for SSAs (Somatostatin Analogues) in the diagnosis and therapy of patients with cervical NECs.

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Distinction of High-Grade Neuroendocrine Carcinoma/Small Cell Carcinoma From Conventional Urothelial Carcinoma of Urinary Bladder

Applied Immunohistochemistry & Molecular Morphology ◽

10.1097/pai.0b013e31820eca9a ◽

2011 ◽

Vol 19 (5) ◽

pp. 395-399 ◽

Cited By ~ 11

Author(s):

Sherry Thompson ◽

Maureen Cioffi-Lavina ◽

Jennifer Chapman-Fredricks ◽

Carmen Gomez-Fernandez ◽

Gustavo Fernandez-Castro ◽

...

Keyword(s):

Urinary Bladder ◽

Urothelial Carcinoma ◽

Cell Carcinoma ◽

Small Cell Carcinoma ◽

Neuroendocrine Carcinoma ◽

Small Cell ◽

High Grade

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Comparative Outcomes in Patients With Small- and Large-Cell Neuroendocrine Carcinoma (NEC) and Mixed Neuroendocrine-Non-Neuroendocrine Neoplasm (MiNEN) of the Stomach

The American Surgeon ◽

10.1177/0003134820950000 ◽

2020 ◽

pp. 000313482095000

Author(s):

Nam Young Choi ◽

Byung-Sik Kim ◽

Sung Tae Oh ◽

Jeong Hwan Yook ◽

Beom Su Kim

Keyword(s):

Clinical Outcomes ◽

Disease Free Survival ◽

Large Cell ◽

Small Cell ◽

Neuroendocrine Neoplasm ◽

Neuroendocrine Neoplasms ◽

High Grade ◽

Intermediate Grade ◽

Free Survival ◽

Neuroendocrine Carcinomas

Background Gastric neuroendocrine carcinomas (NECs), consisting of both large- and small-cell NECs, and mixed adenoneuroendocrine carcinomas (MANECs), including mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs), are a group of high-grade malignancies. Few studies to date have reported clinical outcomes, including prognosis, in patients with these tumors. This study therefore evaluated the clinicopathologic outcomes and prognosis in patients with NECs and MANECs. Methods This study included 36 patients diagnosed with gastric NECs, including 23 with large-cell and 13 with small-cell NECs, and 85 with MiNENs, including 70 with high-grade and 15 with intermediate-grade MiNENs. Clinical outcomes, including overall survival (OS) and disease-free survival (DFS), were assessed. Results DFS was significantly poorer in patients with NEC than in patients with intermediate-grade MiNEN ( P < .05), whereas both OS and DFS were similar in patients with NEC and high-grade MiNEN ( P > .05). Patients with large-cell NEC were more likely to undergo aggressive surgery than patients with high-grade MiNEN ( P < .05). Lymphovascular invasion was more frequent and DFS poorer in patients with large-cell than small-cell NECs ( P < .05 each). Conclusion DFS is significantly poorer in patients with NEC than in patients with intermediate-grade MiNEN and significantly lower in patients with large-cell than small-cell NECs.

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Pulmonary Neuroendocrine Carcinomas

Archives of Pathology & Laboratory Medicine ◽

10.5858/2002-126-0545-pnc ◽

2002 ◽

Vol 126 (5) ◽

pp. 545-553 ◽

Cited By ~ 5

Author(s):

Qin Huang ◽

Alona Muzitansky ◽

Eugene J. Mark

Keyword(s):

Neuroendocrine Tumors ◽

Neuroendocrine Carcinoma ◽

Large Cell ◽

Small Cell ◽

The Body ◽

Low Grade ◽

Typical Carcinoid ◽

Poorly Differentiated Neuroendocrine Carcinoma ◽

Poorly Differentiated ◽

Neuroendocrine Carcinomas

Abstract Context.—Primary pulmonary neuroendocrine tumors are traditionally classified into 3 major types: typical carcinoid (TC), atypical carcinoid (AC), and large cell neuroendocrine carcinoma (LC) or small cell neuroendocrine carcinoma (SC). Confusion arises frequently regarding the malignant nature of TC and the morphologic differentiation between AC and LC or SC. Objective.—To provide clinicopathologic evidence to streamline and clarify the histomorphologic criteria for this group of tumors, emphasizing the prognostic implications. Patients.—To minimize variability in diagnostic criteria and treatment plans, we analyzed a group of patients whose diagnosis and treatment occurred at a single institution. We reviewed 234 cases of primary pulmonary neuroendocrine tumors and thoroughly studied 50 cases of resected tumors from 1986 to 1995. Results.—On the basis of morphologic characteristics and biologic behaviors of the tumors, we agree with many previous investigators that these tumors are all malignant and potentially aggressive. Based on our accumulated data, we have modified Gould criteria and reclassified these tumors into 5 types: (1) well-differentiated neuroendocrine carcinoma (otherwise called TC) (14 cases, with less than 1 mitosis per 10 high-power fields [HPF] with or without minimal necrosis); (2) moderately differentiated neuroendocrine carcinoma (otherwise called low-grade AC) (6 cases, with less than 10 mitoses per 10 HPF and necrosis evident at high magnification); (3) poorly differentiated neuroendocrine carcinoma (otherwise called high-grade AC) (10 cases, with more than 10 mitoses per 10 HPF and necrosis evident at low-power magnification); (4) undifferentiated LC (5 cases, with more than 30 mitoses per 10 HPF and marked necrosis); and (5) undifferentiated SC (15 cases, with more than 30 mitoses per 10 HPF and marked necrosis). The 5-year survival rates were 93%, 83%, 70%, 60%, and 40% for well, moderately, and poorly differentiated, and undifferentiated large cell and small cell neuroendocrine carcinomas, respectively. We found nodal metastasis in 28% of TC in this retrospective review, a figure higher than previously recorded. Conclusion.—Using a grading system and terms comparable to those used for many years and used for neuroendocrine tumors elsewhere in the body, we found that classification of pulmonary neuroendocrine carcinomas as well, moderately, poorly differentiated, or undifferentiated provides prognostic information and avoids misleading terms and concepts. This facilitates communication between pathologists and clinicians and thereby improves diagnosis and management of the patient.

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Neuroendocrine Tumors of Larynx

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348949210100817 ◽

1992 ◽

Vol 101 (8) ◽

pp. 710-714 ◽

Cited By ~ 54

Author(s):

Adel K. El-Naggar ◽

John G. Batsakis ◽

Mario A. Luna

Keyword(s):

Survival Rate ◽

Neuroendocrine Tumors ◽

Small Cell ◽

Neuroendocrine Neoplasm ◽

Neuroendocrine Neoplasms ◽

Neural Basis ◽

Small Cell Neuroendocrine Carcinoma ◽

Typical Carcinoid ◽

Clinical Behavior ◽

Neuroendocrine Carcinomas

Neuroendocrine neoplasms of the larynx have either an epithelial or a neural basis. The former are more numerous and are classified as typical or atypical carcinoids and small cell neuroendocrine carcinomas. Paraganglioma is the sole type of neural neuroendocrine neoplasm. There is a significant worsening of prognosis from typical carcinoid to small cell neuroendocrine carcinoma, with the latter having a dismal 5-year survival rate regardless of therapy. Paragangliomas are the most benign of laryngeal neuroendocrine neoplasms, but their clinical behavior may not be predictable on the basis of their histologic appearance.

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Urothelial carcinoma with villoglandular differentiation (UCVGD) with small cell neuroendocrine carcinoma of urinary bladder

BMJ Case Reports ◽

10.1136/bcr-2018-228017 ◽

2019 ◽

Vol 12 (1) ◽

pp. bcr-2018-228017 ◽

Cited By ~ 2

Author(s):

Shilpy Jha ◽

Suvradeep Mitra ◽

Amit Kumar Adhya ◽

Prasant Nayak

Keyword(s):

Urinary Bladder ◽

Urothelial Carcinoma ◽

Male Patient ◽

Neuroendocrine Carcinoma ◽

Small Cell ◽

High Grade ◽

Small Cell Neuroendocrine Carcinoma ◽

Therapeutic Implications ◽

Muscle Invasive ◽

Aggressive Variant

Urothelial carcinoma with villoglandular differentiation (UCVGD) is a rare aggressive variant of urothelial carcinoma. It is usually associated with high-grade urothelial carcinoma or rarely adenocarcinoma. There is only one other previous report of UCVGD associated with small cell neuroendocrine carcinoma of urinary bladder. We report the second case of UCVGD with small cell neuroendocrine carcinoma of urinary bladder in a 74-year-old non-smoker male patient. The mass was muscle invasive and also invaded the prostate. This entity needs to be confidently diagnosed due to its prognostic and therapeutic implications.

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Neuroendocrine Carcinomas (Carcinoid, Atypical Carcinoid, Small Cell Carcinoma, and Large Cell Neuroendocrine Carcinoma): Current Concepts

Hematology/Oncology Clinics of North America ◽

10.1016/j.hoc.2007.04.011 ◽

2007 ◽

Vol 21 (3) ◽

pp. 395-407 ◽

Cited By ~ 22

Author(s):

Cesar A. Moran ◽

Saul Suster

Keyword(s):

Cell Carcinoma ◽

Small Cell Carcinoma ◽

Neuroendocrine Carcinoma ◽

Large Cell ◽

Small Cell ◽

Large Cell Neuroendocrine Carcinoma ◽

Atypical Carcinoid ◽

Neuroendocrine Carcinomas

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Primary Large Cell Neuroendocrine Carcinoma of the Urinary Bladder

Archives of Pathology & Laboratory Medicine ◽

10.5858/2002-126-1229-plcnco ◽

2002 ◽

Vol 126 (10) ◽

pp. 1229-1232 ◽

Cited By ~ 4

Author(s):

Andrew J. Evans ◽

Jaudah Al-Maghrabi ◽

John Tsihlias ◽

Ginette Lajoie ◽

Joan M. Sweet ◽

...

Keyword(s):

Urinary Bladder ◽

Neuroendocrine Carcinoma ◽

Metastatic Disease ◽

Transurethral Resection ◽

Preoperative Staging ◽

Muscularis Propria ◽

Large Cell ◽

Large Cell Neuroendocrine Carcinoma ◽

Rapid Progression ◽

Solitary Lesion

Abstract Reports of primary large cell neuroendocrine carcinomas of the urinary bladder are few; we identified only 2 cases in the literature. Both of these cases involved male patients with rapid progression of disease culminating in death with widespread metastases. We report a case of primary large cell neuroendocrine carcinoma of the bladder, with an admixed minor element of adenocarcinoma, in an 82-year-old man. This solitary lesion arose in a bladder diverticulum lateral to the left ureteric orifice. Two attempts at transurethral resection were unsuccessful at achieving local control. The patient underwent a partial cystectomy with left-sided pelvic lymphadenectomy following preoperative staging investigations that found no metastatic disease. Pathologically, the tumor invaded into the deep aspect of the muscularis propria, without extension into perivesical fat. The lateral resection margin was microscopically positive for tumor, but no malignancy was found in the pelvic lymph nodes. The adenocarcinoma comprised less than 5% of total tumor volume, and areas of transition between the neuroendocrine and adenocarcinoma components were apparent. The patient developed a local recurrence 8 months postoperatively, which was managed by a combination of transurethral resection and radiation therapy. Currently, the patient has no evidence of local or metastatic disease 2 years after initial diagnosis.

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