Arias-Stella reaction

Editorial Board Member: Ayse Ayhan, M.D., Ph.D.
Laura Ardighieri, M.D.

Topic Completed: 1 March 2017

Minor changes: 4 October 2021

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PubMed search: Arias-Stella reaction uterus

Laura Ardighieri, M.D.
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Cite this page: Ardighieri L. Arias-Stella reaction. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/uterusariasstella.html. Accessed December 7th, 2021.
Definition / general
  • Distinctive (usually focal) benign nuclear enlargement of "exaggerated hyperplastic" appearance characterized by centronuclear vacuolization, typically associated with pregnancy or hormone effect
  • Typically found in the endometria of post abortion curettings (20% - 70%) of intra or extrauterine pregnancies, moles and choriocarcinoma; also in adenomyosis and adenomyomatous polyps of the uterus or endocervix; in endocervical polyps, epithelia of fallopian tube, foci of endometriosis, paraovarian and paratubal cysts, vaginal adenosis
  • There is no mass
  • This finding may provide initial histologic "clue" of ectopic pregnancy (Arch Gynecol Obstet 2007;276:47)
Essential features
  • Pseudoneoplastic glandular response of the female genital tract, first described by Javier Arias-Stella in 1954 as atypical endometrial changes associated with the presence of chorionic tissue
  • Characterized by enlarged glands with abundant clear or eosinophilic cytoplasm and vacuolization associated with hyperchromatic, pleomorphic and smudged nuclei - "hobnail" appearance
  • Frequently occurs as a reaction in the endometrium of women of reproductive age with intrauterine / extrauterine pregnancy and gestational trophoblastic disease
  • The finding of Arias-Stella effect in secretory endometrium is not diagnostic of intrauterine (even extrauterine) pregnancy
  • Rarely can be seen in nonpregnant patients on hormonal therapy (oral contraceptives, ovulation inducing drugs and hormone replacement therapies and phytoestrogens) and more rarely in patients without hormonal treatment
  • Described also in extraendometrial sites: endocervix, fallopian tube, endometriosis (cervix, ovarian, peritoneal, subcutaneous, umbilica, urinary bladder), paraovarian and paratubal cysts, vaginal adenosis, ovarian germinal inclusion cysts, luteal cysts of puerperium and gestation and even in some ovarian mucinous neoplasms
  • Usually easy to recognize because it predominantly affects young and pregnant patients; however, it may occasionally raise concern for carcinoma if detected in nonpregnant or older patients
  • No need for treatment since it is a benign condition that usually regresses post partum
  • Synonyms: Arias-Stella phenomenon / Arias-Stella change / Arias-Stella effect
Clinical features
  • Incidental finding
  • Increased serum levels of beta human chorionic gonadotropin (β-hCG) if associated with pregnancy
Radiology description
  • Ultrasonography can reveal a pregnancy (intra- or extrauterine)
Prognostic factors
  • Excellent prognosis (benign condition)
Case reports
Gross description
  • Does not typically form mass lesion
  • May extensively involve preexisting polyp
Microscopic (histologic) description
  • Intraglandular papillary epithelial tufts
  • Some cases shows hobnail growth pattern, with nuclei placed at the bulbous shaped apical portion of the cytoplasm
  • Vacuoles are formed within these tufts and there is a loss of cellular polarity
  • Dr. Arias-Stella classified the histologic variants into five types:
    • Minimal atypia: characterized by mild nuclear enlargement
    • Early secretory pattern: marked nuclear enlargement, subnuclear and supranuclear vacuoles
    • Secretory or hypersecretory pattern: enlarged nuclei and intense and diffuse cytoplasmic vacuolization
    • Regenerative, proliferative or nonsecretory pattern: nuclei with a vesicular configuration with glands showing no / minimal secretory activity
    • Monstrous cell pattern: nuclei show giant and bizarre forms with homogenous chromatin and frequent pseudoinclusions
  • Reference: Adv Anat Pathol 2002;9:12
Microscopic (histologic) images

Contributed by Ayse Ayhan, M.D., Ph.D.

Various images

Images hosted on other servers:

Various images

Cytology description
  • Cellular enlargement, mainly of the nucleus, to double or many times normal size
  • Hypertrophied nuclei of ovoid or round shape with granular or vesicular viable chromatin, an irregular outline and hyperchromatic appearance or a compact, pyknotic pattern
  • Some cases can have optically clear nuclei or nuclear pseudoinclusions
  • Abundant cytoplasm may be densely eosinophilic or clear and vacuolated
  • Normal nuclear to cytoplasmic ratio
  • Mitotic figures in 10% to 15% of cases; rarely can be atypical or numerous (PMID: 766510, Arch Pathol Lab Med 1981;105:116)
  • Reference: Adv Anat Pathol 2002;9:12
Positive stains
Electron microscopy description
Molecular / cytogenetics description
Differential diagnosis
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