Cervix
Carcinoma
Typical carcinoid tumor

Author: Sucheta Srivastava, M.D.

Revised: 1 October 2018, last major update August 2018

Copyright: (c) 2003-2018, PathologyOutlines.com, Inc.

PubMed Search: Carcinoid tumor cervix

Related topics: Atypical carcinoid
Cite this page: Srivastava, S. Typical carcinoid tumor. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/cervixcarcinoidtumor.html. Accessed October 15th, 2018.
Definition / general
  • Low grade tumor which includes both grade 1 and grade 2 neuroendocrine tumors
  • 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 tumors exhibit characteristic neuroendocrine and organoid differentiation
  • They lack nuclear atypia, mitotic figures and necrosis
  • No specific recommendation for Ki67 labelling index and 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
  • 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)
    • Low grade neuroendocrine tumor (typical carcinoid, atypical carcinoid tumor)
    • High grade neuroendocrine carcinoma (small cell neuroendocrine carcinoma, large cell neuroendocrine carcinoma)
    • Adenocarcinoma admixed with neuroendocrine carcinoma
Epidemiology
  • Overall, cervical neuroendocrine tumors (NET) represent ~2% of all cervical malignancies (Case Rep Oncol 2017;10:737)
  • Cervical low grade NETs 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 and etiology
  • Neuroendocrine differentiation occurs within neoplasms arising from the cervical epithelium
  • Cells that express neuroendocrine markers are present in some cases of cervical adenocarcinoma in situ and could be the precursor of cervical neuroendocrine tumors
  • High risk HPV can be identified in most cervical NETs; association is more robust for atypical carcinoids (Gynecol Oncol 1999;72:3)
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 and are more often seen in atypical carcinoid (Gynecol Oncol Case Rep 2013;7:4)
Diagnosis
  • Development of immunohistochemistry panels and plasma assays for peptides and amines, as well as the widespread use of Octreoscan and PET / CT, has significantly enhanced the identification and diagnosis of neuroendocrine tumors
Laboratory
  • Low grade neuroendocrine tumors may produce a variety of peptides such as calcitonin, gastrin, serotonin, substance P, vasoactive intestinal peptide, pancreatic polypeptide, somatostatin, adrenocorticotrophic hormone, β-melanocyte-stimulating hormone and histamine 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 and 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
Treatment
Gross description
  • Macroscopic appearance of NETs 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
  • Grade 1 tumors are typically 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 nuclear atypia, mitotic figures and necrosis
  • Mitotic activity is generally < 2 mitotic figures / 10 HPF
  • No specific evidence for the formulaic use of Ki67 labelling index and mitotic count for the grading of cervical neuroendocrine tumors, as is recommended for gastroenteropancreatic tumors (Case Rep Oncol 2017;10:737, Gynecol Oncol 2017;144:637)
Microscopic (histologic) images

Images hosted on PathOut server:

Contributed by Branko Perunovic, M.D.

Ribbons of tumor cells

Glandular features

Cords and glands of tumor cells



Images hosted on other servers:
Missing Image

Cervical polyp occupied by carcinoid tumor

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Synaptophysin+

Small intestine

Negative stains
Molecular / cytogenetics description
  • Most frequent allelic loss in NETs is localized 3p deletion
  • Occasional 9p21 deletions have also been identified (Gynecol Oncol 1999;72:3)
Differential diagnosis
  • Metastatic carcinoid from other locations especially GI tract
Board review question #1
Which of the following is true?

  1. Typical carcinoids are commonly positive for high risk HPV
  2. Typical carcinoids commonly present with carcinoid syndrome
  3. Typical carcinoids frequently metastasize
  4. Typical carcinoids lack nuclear atypia, mitotic figures and necrosis
Board review answer #1
D. Typical carcinoids lack nuclear atypia, mitotic figures and necrosis
Board review question #2
Which of the following is false?

  1. Necrosis is an important feature of typical carcinoid
  2. Presence of neuroendocrine component (even in combination with SCC or adenocarcinoma) needs to be documented in pathology report
  3. There are no specific Ki67 labeling index criteria to define typical carcinoids
  4. Typical carcinoids generally follow an indolent course
Board review answer #2
A. Necrosis is an important feature of typical carcinoid