Typical carcinoid tumor

Cervix

Other epithelial tumors

Author: Sucheta Srivastava, M.D.

Editorial Board Member: Carlos Parra-Herran, M.D.

Editor-in-Chief: Debra L. Zynger, M.D.

Topic Completed: 1 August 2018

Minor changes: 5 March 2020

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PubMed Search: Carcinoid tumor cervix

Related topics: Atypical carcinoid

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Table of Contents

Cite this page: Srivastava S. Typical carcinoid tumor. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cervixcarcinoidtumor.html. Accessed January 20th, 2021.

Definition / general

Grade 1 neuroendocrine tumor
Recommended terminology for neuroendocrine tumors arising in the cervix is similar to that used for gastroenteropancreatic neuroendocrine tumors
Same architectural and cytological features as neuroendocrine tumors at other sites

Essential features

Low grade (grade 1) neuroendocrine tumor
Characteristic neuroendocrine and organoid differentiation without nuclear atypia, mitotic figures or necrosis
No specific recommendation for Ki67 labelling index or mitotic count
Generally follow an indolent course; however, they retain the potential for metastatic spread

Terminology

For typical carcinoid tumor: low grade neuroendocrine tumor, grade 1
For atypical carcinoid tumor: low grade neuroendocrine tumor, grade 2 or grade 3 (Modern Pathology 2018;31:1770)
Updated 2014 World Health Organization (WHO) classification of neuroendocrine tumors of female reproductive organs provides following terminology for uterine cervix which is more in line with the terminology used for GI tract (Curr Oncol Rep 2017;19:59) and aligns with the recently proposed unified nomenclature by the International Agency for Research on Cancer (IARC) and World Health Organization (WHO) (Modern Pathology 2018;31:1770)
- Low grade neuroendocrine tumor (typical carcinoid, atypical carcinoid tumor), corresponding to the term “Neuroendocrine Tumor” in the 2018 terminology
- High grade neuroendocrine carcinoma (small cell neuroendocrine carcinoma, large cell neuroendocrine carcinoma)corresponding to the term “Neuroendocrine Carcinoma” in the 2018 terminology
- Adenocarcinoma admixed with neuroendocrine carcinoma

Epidemiology

Overall, cervical neuroendocrine tumors represent ~2% of all cervical malignancies (Case Rep Oncol 2017;10:737)
Cervical low grade neuroendocrine tumors are extremely rare, accounting for less than 0.5% of cervical cancers
Most patients are in fourth to fifth decade
Patients tend to be younger, more often white / Caucasian compared to more common cervical carcinomas (squamous and adenocarcinoma)

Pathophysiology

High risk HPV sequences (types 16 and 18) were not present in typical carcinoid tested in some of the studies however their numbers are very small for any reliable generalization (Gynecol Oncol 1999;72:3)
High risk HPV sequences were present in large cell NEC and small cell neuroendocrine carcinomas tested in these studies (Am J Surg Pathol 2004;28:901)

Clinical features

Vaginal bleeding or discharge or detection of a cervical mass, post coital spotting, abnormal Pap smear (Acta Pathol Jpn 1987;37:1183)
Symptoms related to ectopic hormone production or carcinoid syndrome are extremely rare for carcinoid tumor (Gynecol Oncol Case Rep 2013;7:4)

Laboratory

Plasma assays for peptides such as calcitonin, gastrin, serotonin, substance P, vasoactive intestinal peptide, pancreatic polypeptide, somatostatin, adrenocorticotrophic hormone, β-melanocyte-stimulating hormone and histamine may be elevated, although it is not related to clinical symptoms
Urinary levels of 5-HIAA may be elevated and 24 hour urinary 5-HIAA may be useful
Chromogranin A is present in the neurosecretory vesicles of neuroendocrine tumor cells and may be detectable in the plasma of such patients
Serum Chromogranin A is a more sensitive and broadly applicable tumor marker for neuroendocrine tumors than is urinary 5-HIAA but it is less specific
Chromogranin A levels are higher in patients with diffuse metastases than localized disease or isolated hepatic involvement; higher levels may be associated with a poorer prognosis
Data on the correlation of plasma Chromogranin A levels with treatment response and on their prognostic value are not available for cervical carcinoids (Case Rep Oncol 2017;10:737)

Prognostic factors

Grade 1 neuroendocrine tumors generally follow an indolent course; however, they retain the potential for metastatic spread and their prognosis is difficult to evaluate due to their rarity

Case reports

33 year old woman with primary carcinoid of the uterine cervix (Cancer 1979;43:535)
40 year old woman presented with abnormal cervical cytology (Acta Cytol 1990;34:119)
43 year old woman with a nonmetastatic cervical carcinoid (Case Rep Oncol 2017;10:737)
60 year old white woman with histochemical and ultrastructural examinations (Acta Obstet Gynecol Scand 1983;62:539)
62 year old woman with cervical carcinoid tumor without endocrine symptoms (Br J Obstet Gynaecol 1981;88:1056)
Rare case of carcinoid tumor of the uterine cervix associated with adenocarcinoma (Acta Pathol Jpn 1987;37:1183)

Treatment

There are currently no recommendations regarding treatment due to rarity of the cases (J Clin Endocrinol Metab 1999;84:4209, Gynecol Oncol Case Rep 2013;7:4)
Most reported cases were initially treated with radical hysterectomy (Cancer 1979;43:535, Gynecol Oncol 1999;72:3, Acta Obstet Gynecol Scand 1983;62:539, World J Surg 2005;29:92, Gynecol Oncol 2011;122:190)
Octreotide scan (somatostatin analog scintigraphy) can be used to predict response to somatostatin analogs and also inversely correlates to chemotherapy response (Gynecol Oncol 2011;122:190)

Gross description

Macroscopic appearance is not distinctive
Average reported size range is 0.5 - 11 cm in diameter
Lesions are commonly large, sometimes with a barrel shaped appearance

Microscopic (histologic) description

Well to moderately differentiated and contain neurosecretory granules
Growth patterns can be organoid, trabecular, nodular, nests / islands or cord-like
Rosette-like structures are common
Cells are round to oval with abundant cytoplasm, elongated nuclei, characteristic finely granular chromatin and visible to prominent nucleoli
Cells are commonly epithelioid but can be spindled
Lack of nuclear atypia, mitotic figures and necrosis
Mitotic activity has been traditionally assessed in number of mitoses per high power field; however, the 2018 consensus terminology recommends that mitotic count should be expressed as mitoses per mm2 area, ideally counted in up to 10mm2 to assure accuracy (Modern Pathology 2018;31:1770)
- In typical carcinoid tumors, mitotic activity is absent
No specific evidence for the formulaic use of Ki67 labelling index or mitotic count for grading (Case Rep Oncol 2017;10:737, Gynecol Oncol 2017;144:637)

Positive stains

Synaptophysin, chromogranin, CD56 and neuron specific enolase (NSE), cytokeratin (Case Rep Oncol 2017;10:737, Gynecol Oncol 2017;144:637)

Negative stains

p63 (positive in SCC)
Inhibin / Calretinin (sex cord stromal tumor)
LCA (lymphoproliferative disorder)
S100, desmin, myogenin

Molecular / cytogenetics description

High risk HPV sequences (types 16 and 18) were not present in typical carcinoid tested in some of the studies however, their numbers are very small for any reliable generalization (Gynecol Oncol 1999;72:3)
They usually do not harbor the mutations seen in large cell NEC and small cell carcinoma such as allelic losses and p53 gene abnormalities (Gynecol Oncol 1999;72:3)

Differential diagnosis

Metastatic carcinoid from other locations especially GI tract

Additional references

World J Surg 2005;29:92, J Exp Clin Cancer Res 2001;20:327, Arch Pathol Lab Med 1997;121:34, Ann Diagn Pathol 2017;29:11, Gynecol Oncol 2011;122:190, Gynecol Oncol 1988;30:114, Zhonghua Fu Chan Ke Za Zhi 2015;50:198

Board review style question #1

Which of the following is true?

Typical carcinoids are commonly positive for high risk HPV
Typical carcinoids commonly present with carcinoid syndrome
Typical carcinoids frequently metastasize
Typical carcinoids lack nuclear atypia, mitotic figures and necrosis

Board review style answer #1

D. Typical carcinoids lack nuclear atypia, mitotic figures and necrosis

Board review style question #2

Which of the following is false?

Necrosis is an important feature of typical carcinoid
Presence of neuroendocrine component (even in combination with SCC or adenocarcinoma) needs to be documented in pathology report
There are no specific Ki67 labeling index criteria to define typical carcinoids
Typical carcinoids generally follow an indolent course

Board review style answer #2

A. Necrosis is an important feature of typical carcinoid

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