Uterus

Nontumor

Arias-Stella reaction


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Laura Ardighieri, M.D.

Last staff update: 5 December 2022 (update in progress)

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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 10th, 2022.
Definition / general
  • Reactive phenomenon of the endometrium induced by high dose estrogen / progesterone in the setting of pregnancy, gestational trophoblastic disease or secondary to hormone therapy, characterized by cytomegalia and nuclear enlargement of endometrial glands
  • Typically found in the endometria of postabortion curettings of intrauterine or extrauterine pregnancies or with gestational trophoblastic disease; however, it can occur anywhere in the epithelium of female genital tract during pregnancy and under hormonal intake
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; frequently occurs as a reaction in the endometrium of women of reproductive age with intrauterine / extrauterine pregnancy and gestational trophoblastic disease (AMA Arch Pathol 1954;58:112)
  • Endometrial glands are lined by enlarged or hobnail cells, characterized by abundant eosinophilic, cleared to vacuolated cytoplasm and by hyperchromatic, pleomorphic and smudged nuclei with hobnail appearance (Am J Surg Pathol 2004;28:608)
    • Nuclear to cytoplasmic ratio is maintained
    • Phenomenon may be focal or extensive and may involve part of a gland or an entire gland
  • Most important differential diagnosis is clear cell carcinoma (Am J Surg Pathol 2019;43:325)
  • 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 (Int J Gynecol Pathol 1994;13:241)
  • 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 (Diagn Cytopathol 2005;32:94)
  • Described also in extraendometrial sites: endocervix, fallopian tube, endometriosis (cervix, ovarian, peritoneal, subcutaneous, umbilical, 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 (Am J Clin Pathol 1991;95:892, Arch Gynecol Obstet 2007;276:47, Pathol Res Pract 2009;205:653, Acta Cytol 2001;45:627, Adv Anat Pathol 2002;9:12, Acta Obstet Gynecol Scand 1986;65:505)
Terminology
  • Arias-Stella phenomenon, Arias-Stella change, Arias-Stella effect
ICD coding
  • ICD-11: GA1Y - other specified noninflammatory disorders of female genital tract
Epidemiology
  • Relatively common phenomenon
  • Most commonly occurs in reproductive aged women and in the background of pregnancy; however, it may be seen in women of all ages and in any type of hormonal alteration (exogenous and endogenous)
Sites
Pathophysiology
  • Represents a cellular transdifferentiation process: conversion of a differentiated cell type into another cell type (Adv Anat Pathol 2002;9:12)
  • Hormone related atypical endometrial reaction, related to the effects of estrogens and progesterone acting simultaneously (Adv Anat Pathol 2002;9:12)
  • Very rarely, Arias-Stella reaction (ASR) can occur in the absence of pregnancy or hormonal intake, also in foci of endometriosis (J Clin Diagn Res 2016;10:ED03)
Etiology
Clinical features
  • Incidental finding
Diagnosis
Laboratory
  • Increased serum levels of beta human chorionic gonadotropin (βhCG) in gestational cases
Radiology description
  • Ultrasonography can reveal a pregnancy (intrauterine or extrauterine)
Prognostic factors
  • Benign condition that typically regresses postpartum
Case reports
Treatment
  • Benign condition that does not need treatment
Gross description
  • Does not typically form mass lesion
  • May extensively involve pre-existing polyp
Frozen section description
  • Since Arias-Stella can be found anywhere in the female genital tract and outside it in ectopic endometrial glands (e.g., in endometriotic lesions), in view of the presence of giant cells with coarse chromatin and macronucleoli, a false positive diagnosis of malignancy can be made during intraoperative examination if the clinician does not provide information regarding current or recent pregnancy or hormonal treatment (J Clin Diagn Res 2016;10:ED03, AMA Arch Pathol 1954;58:112)
  • ASR can occasionally be mistaken for clear cell carcinoma; differentiation from it is made by the lack of stromal invasion, as well as by the absence of the classic tubular and papillary areas typical of clear cell carcinoma and the lack of mitotic activity (Am J Surg Pathol 2019;43:325)
  • In pregnant patients, diagnosis of malignancy should be made with caution when evaluating frozen sections
Microscopic (histologic) description
  • Endometrial glands lined by large polyhedral cells with abundant eosinophilic cytoplasm with large hyperchromatic, pleomorphic and smudged nuclei
  • Focal or diffuse: can involve portion of a gland, a single gland or a different number of glands
  • Affected glands may have micropapillary or cribriform growth and intraglandular papillary epithelial tufts; occasionally they can be confluent cells protruding into the lumen, with nuclei placed at the bulbous shaped apical portion of the cytoplasm, imparting hobnail appearance
  • Absence of stromal invasion
  • Dr. Arias-Stella classified the histologic variants into 5 types (Adv Anat Pathol 2002;9:12):
    • 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
  • Mitotic figures in the ASR are rare and thus, frequent or atypical mitoses should raise concern for adenocarcinoma
Microscopic (histologic) images

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

Nuclear enlargement, rather normal N/C and intense subnuclear / supranuclear vacuoles

Hobnail growth pattern

Napsin A positivity

Cytology description
  • Cellular enlargement, to double or many times the normal size
  • Abundant eosinophilic, clear to vacuolated cytoplasm
  • Hypertrophied and hyperchromatic nuclei of ovoid or round shape with irregular nuclear contours and variable chromatin patterns (smudgy, open, even)
  • Normal nuclear to cytoplasmic ratio
  • Mitotic figures in 10 - 15% of cases; rarely can be atypical or numerous (Arch Pathol Lab Med 1981;105:116)
Positive stains
Negative stains
Electron microscopy description
Molecular / cytogenetics description
Sample pathology report
  • Endometrium, biopsy:
    • Gestational endometrium with Arias-Stella reaction
Differential diagnosis
Board review style question #1

The finding in the figure above is found in gestational endometrium. What is the diagnosis?

  1. Arias-Stella reaction
  2. Clear cell carcinoma
  3. Endometrioid carcinoma
  4. Endometritis
Board review style answer #1
A. Arias-Stella reaction

Comment Here

Reference: Arias-Stella reaction
Board review style question #2
Where can the Arias-Stella phenomenon occur?

  1. Anywhere in the female genital tract
  2. In the endometrium only
  3. In the uterine cervix
  4. Only in gestational endometrium
Board review style answer #2
A. Anywhere in the female genital tract

Comment Here

Reference: Arias-Stella reaction
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