Cervix - Cytology
Carcinoma
Small cell (neuroendocrine / undifferentiated) carcinoma

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

Revised: 3 May 2017, last major update May 2015

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

PubMed Search: Small cell carcinoma [title] cervix
Cite this page: Small cell (neuroendocrine / undifferentiated) carcinoma. PathologyOutlines.com website. http://pathologyoutlines.com/topic/cervixcytologysmallcellca.html. Accessed September 23rd, 2017.
Definition / general
  • 1-5% of invasive cervical cancers
  • Poor prognosis with rapid disease progression
  • May develop after a negative Pap test to an advanced stage between screenings (Case Rep Pathol 2014;2014:971464)
Epidemiology
  • Women ages 25 to 87 years (median ~42 years)
  • Mostly pure form, but may coexist with cervical squamous cell carcinoma or adenocarcinoma (Cytojournal 2013;10:17)
Pathophysiology
  • HPV 18 > HPV 16
Clinical features
Prognostic factors
Gross description
  • Erythematous cervix with small exophytic mass
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

Negative stains
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