Cervix
Carcinoma
Small cell (neuroendocrine / undifferentiated) carcinoma

Authors: Branko Perunovic, M.D., Ashwyna Sunassee, M.D. (see Authors page)
Editor: Ryan Askeland, M.D.

Revised: 4 November 2017, last major update May 2007

Copyright: (c) 2003-2017, PathologyOutlines.com, Inc.

PubMed Search: Small cell carcinoma [title] cervix

Cite this page: Cervix - Small cell (neuroendocrine / undifferentiated) carcinoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/cervixsmallcell.html. Accessed December 17th, 2017.
Definition / general
  • Rare (1 - 5% of invasive cervical carcinomas)
  • Clinically aggressive with rapid metastases and poor prognosis
Terminology
  • Amphicrine carcinoma: small cell carcinoma combined with squamous cell carcinoma or adenocarcinoma
Epidemiology
Pathophysiology
  • Coexisting SIL is rare; endocrine cell hyperplasia may be a precursor lesion
  • HPV 18 > HPV 16
Clinical features
  • Vaginal bleeding, post-coital spotting, lower abdominal pain (J Clin Diagn Res 2014;8:147)
  • Cervical mass / bulkiness
  • Frequently presents with parametrial invasion and pelvic lymph node metastases
  • Paraneoplastic syndromes include Cushing syndrome, carcinoid syndrome, SIADH, hypoglycemia (Cytojournal 2013;10:17)
  • Mostly pure form, but may coexist with cervical squamous cell carcinoma or adenocarcinoma (Cytojournal 2013;10:17)
  • May develop after a negative Pap test to an advanced stage between screenings (Case Rep Pathol 2014;2014:971464)
  • 5 year survival is 30 - 40%; relapse in 2/3 at median 8 months (Gynecol Oncol 2004;93:27), poor prognostic factors are smoking and high stage (Cancer 2003;97:568), focal glandular differentiation does not affect prognosis
Prognostic factors
Case reports
Treatment
  • Radical hysterectomy with bilateral lymphadenectomy, radiation therapy and chemotherapy
Gross images
  • Erythematous cervix, often barrel shaped, with small exophytic mass
  • May be ulcerative and infiltrative
Microscopic (histologic) description
  • Loose aggregates of uniform small cells with indistinct cell borders, scant cytoplasm, hyperchromatic nuclei with fine granular chromatin, nuclear molding, indistinct nucleoli, extensive mitotic activity, single cell necrosis
  • May form sheets with small acini resembling rosettes
  • Necrosis common
  • Vascular invasion in 9%
  • Resembles counterpart in lung
  • Patterns include insular (solid nests / islands of cells with peripheral palisading and retraction of stroma), perivascular and thick trabeculae with serpiginous (wavy) growth
  • Variable amyloid deposition
  • May have minor (< 10%) component of glandular or squamous differentiation
  • Often no associated inflammation
Microscopic (histologic) images

Images hosted on PathOut server:

Sheets of small cells with scant cytoplasm and hyperchromatic nuclei


Case of the Week #327:

H&E


CK7

p16

Chromogranin

Synaptophysin


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H&E


Cytology description
  • Pap slides are usually moderately to highly cellular
  • Cells appear in loosely cohesive multidimensional aggregates and sheets as well as single and dispersed
  • Cells are monotonous in size (approximately 2x intermediate squamous cell nuclei) (Case Rep Pathol 2014;2014:971464)
  • Very high nuclear/cytoplasmic ratios with delicate rims of amphophilic cytoplasm
  • Nuclei have finely granular/stippled chromatin, with nuclear molding and smear artifact
  • Mitotic figures common
  • Background is mostly clear but may have granular proteinaceous diathesis material (clinging diathesis) and apoptotic degenerated single tumor cells (Case Rep Pathol 2014;2014:971464, Acta Cytol 1998;42:978, Acta Cytol 2003;47:56, Diagn Cytopathol 2001;24:46)
Cytology images

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Lesional cells, Pap

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Single necrotic cells, Pap

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Amphophilic cytoplasm

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Large aggregates of malignant cells


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Malignant cells loosely cohesive

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Scant cytoplasm

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PanCK

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Synaptophysin


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p16

Positive stains
Negative stains
Electron microscopy description
  • Cells are tightly packed with close apposition of cell membranes
  • Dense core secretory granules
Molecular / cytogenetics description
  • Frequent loss of heterozygosity at 3p and 11p
Differential diagnosis
  • Three specific cytomorphological criteria are the most reliable features for separating small cell from non-small cell carcinoma:
    • Nuclear molding
    • Finely granular "salt and pepper" chromatin
    • Scant delicate cytoplasm
  • Follicular cervicitis: reactive polymorphous population including lymphocytes in every stage of maturation as well as germinal center macrophages containing phagocytosed cellular debris
  • Lymphoma: cells individually scattered and loosely arranged in a dirty background with inflammatory cells; nuclear molding infrequent but high grade lymphoma may have pseudomolding which resembles real molding
  • Rhabdomyosarcoma or other small blue cell sarcomas
  • Squamous cell carcinoma: tumor cells arranged singly or in syncytial aggregates with smooth cell borders, high N/C ratio, more cytoplasm than small cell carcinoma, coarsely granular hyperchromatic nuclei with irregularly distributed chromatin, nuclear molding not seen
  • Carcinoid tumor
  • Metastatic carcinoma: lung or other sites
Additional references