Other epithelial tumors

Atypical carcinoid tumor

Editorial Board Member: Carlos Parra-Herran, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Sucheta Srivastava, M.D.

Topic Completed: 1 August 2018

Minor changes: 5 May 2021

Copyright: 2018-2021, PathologyOutlines.com, Inc.

PubMed Search: Atypical carcinoid [title] tumors

See Also: Typical carcinoid tumor

Sucheta Srivastava, M.D.
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Cite this page: Srivastava S. Atypical carcinoid tumor. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cervixcarcinoidatypical.html. Accessed November 29th, 2021.
Definition / general
  • Neuroendocrine tumor with cytologic atypia and increased mitotic activity compared to typical carcinoid
  • Classified as low grade neuroendocrine tumor (previously grade 2 and grade 3 neuroendocrine tumor) (Modern Pathology 2018;31:1770)
Essential features
  • Aggressive tumor that frequently shows subclinical hematogenous and lymphatic metastases, even in early disease
  • Metastasize to liver and may present with carcinoid syndrome
  • Urine 5-HIAA levels may be elevated
  • Frequently coexist with other more common types of cervical carcinoma such as adenocarcinoma or squamous cell carcinoma
  • 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
  • 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 the following terminology for uterine cervix, which is more in line with the terminology used for GI tract (Kurman: WHO Classification of Tumours of the Female Reproductive Organs, 4th Edition, 2014, Curr Oncol Rep 2017;19:59)
    • Low grade neuroendocrine tumor (carcinoid, atypical carcinoid tumor), corresponding to the term Neuroendocrine Tumor in the 2018 unified nomenclature
    • High grade neuroendocrine carcinoma (small cell neuroendocrine carcinoma, large cell neuroendocrine carcinoma), corresponding to the term Neuroendocrine Carcinoma in the 2018 unified nomenclature
    • Adenocarcinoma admixed with neuroendocrine carcinoma
  • Atypical carcinoid tumor encompasses what is classified as low grade neuroendocrine tumor, grade 2 and grade 3 in the 2018 proposed unified classification of neuroendocrine tumors (Modern Pathology 2018;31:1770); however, definitions for grade 2 versus grade 3 are not provided
Clinical features
  • May present with vaginal bleeding or discharge, detection of a cervical mass, postcoital spotting, abnormal Pap smear (Gynecol Oncol Case Rep 2013;7:4)
  • Symptoms related to ectopic hormone production or carcinoid syndrome can be seen and are more common than in typical carcinoid (Gynecol Oncol Case Rep 2013;7:4)
Radiology description
  • Cross sectional imaging including either a triphasic CT or an MRI should be performed to evaluate the extent of the disease
  • Somatostatin receptor scintigraphy (SRS) can localize the tumor, with an overall sensitivity as high as 90%
  • Uptake of radiolabeled octreotide is predictive of a clinical response to therapy with somatostatin analogues
  • FDG positron emission tomography (PET) may be useful for initial staging
  • Octreoscan appears more sensitive than FDG PET
  • PET / CT does not provide any meaningful diagnostic information except with aggressive tumors (J Obstet Gynaecol Res 2011;37:636)
Prognostic factors
  • Considered aggressive with metastases to liver and extension outside the uterus
  • Paucity of cases with reported follow-up yields uncertain prognosis; however, considered to have potential for aggressive behavior since metastases to liver and extension outside the uterus have been reported
  • Outcome is considered to be intermediate between carcinoid tumor and high grade neuroendocrine carcinoma
  • Most commonly present as stage 1 disease in contrast to squamous cell carcinoma, which usually presents as stage 2 disease
  • Prognosis is mainly dependent on tumor stage
  • Relationship between size and metastatic propensity has not been established
  • Uncertain impact of mitotic rate or Ki67 labeling index
  • Most patients with recurrent disease develop metastases (Gynecol Oncol 2017;144:637, Case Rep Oncol 2017;10:737, Gynecol Oncol Case Rep 2013;7:4)
Case reports
Gross images

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Hysterectomy specimen

Microscopic (histologic) description
  • Insular and trabecular growth
  • Increased mitotic activity (5 - 10 mitotic figures / 10 high powered fields) (Semin Diagn Pathol 2013;30:224)
  • The impact of the mitotic rate per 10 HPF and Ki67 labeling index on the prognosis of neuroendocrine tumors has been evaluated in multiple studies, which included NET of gastroenteropancreatic or bronchopulmonary origin mostly
  • The same might be true for cervical carcinoids but the overall small sample size prohibits any reliable generalization of patient outcome (Semin Diagn Pathol 2013;30:224)
  • Mild to moderate nuclear pleomorphism and focal necrosis
  • Immunohistochemical evidence of neuroendocrine differentiation is required for diagnosis (Case Rep Oncol 2017;10:737, Gynecol Oncol 2017;144:637, Semin Diagn Pathol 2013;30:224)
Negative stains
Molecular / cytogenetics description
Differential diagnosis
Board review style question #1
    Which of the following is not a feature of atypical carcinoid (low grade neuroendocrine tumor, grade 2)?

  1. Carcinoid syndrome
  2. Increased mitotic activity
  3. Elevated Ki67 index (> 1%)
  4. Moderate cytological atypia
  5. Well differentiated morphology
Board review style answer #1
C. Elevated Ki67 index. In the gynecologic tract, the prognostic value of Ki67 has not been elucidated; thus it is not used for classification purposes.

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Reference: Atypical carcinoid tumor
Board review style question #2
Atypical cervical carcinoid is positive for which of the following?

  1. CD56
  2. p63
  3. S100
  4. Desmin
Board review style answer #2
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