A 39-year-old woman with persistent abnormal uterine bleeding undergoes a hysterectomy following completion of childbearing. The 190-gram uterus (7.5 x 6.0 x 5.0 cm) is asymmetrical on gross examination and on cut section the myometrium is firm, coarsely trabecular, and measures up to 1.5 cm in thickness. Multiple pinpoint hemorrhagic cysts are noted within the uterine wall. The endometrial lining varies in thickness up to 1.0 cm and is tan-white and "gelatinous" with focal hemorrhage.

Master List of Diagnoses

  • Adenomyosis with pseudodecidual change
  • Malacoplakia
  • Metastatic carcinoma
  • Müllerian adenosarcoma
  • Placental site trophoblastic tumor
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This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2017, Case 35, and is adenomyosis with pseudodecidual change of the uterus.

Criteria for Diagnosis and Comments

Sections from the submitted case are from the uterine wall; in some sections the endometrial lining is also present. Within the myometrium are variably-sized islands of tissue composed of both a glandular and stromal component. The glandular component is banal, composed predominantly of a single layer of low columnar to cuboidal to flattened epithelium. The glands are typically small and round, but in some sections are cystic with variably irregular outlines. The stroma also has a variable appearance being composed predominantly of cells with abundant eosinophilic cytoplasm and round to oval vesicular nuclei with small nucleoli; in some foci, the stroma is spindled with scant cytoplasm and smaller nuclei. Mitotic activity is scarce. In some sections, the myometrium forms rounded masses surrounding these islands corresponding to myometrial hypertrophy. The overall findings are those of adenomyosis; the changes in the endometrial glands and stroma are indicative of pseudo-decidual change secondary to hormonal (progestin) treatment.

Adenomyosis is a benign process in which endometrial tissue, typically both glands and stroma, is present within the myometrium. It is relatively common, with a prevalence of approximately 25%, typically occurring in the late reproductive years. Patients often have menorrhagia or dysmenorrhea, but these symptoms are not specific as they are seen in a variety of gynecologic disorders.

On gross examination, the uterus is typically enlarged, particularly for patients with significant clinical symptoms. Uterine enlargement, which is secondary to associated myometrial hypertrophy, may be global with diffuse expansion of the myometrium, or it may be localized. In the latter scenario, adenomyosis may mimic a leiomyoma. Adenomyosis may be visible on cut section of the myometrium as pinpoint hemorrhagic cysts within a coarsely trabeculated uterine wall. This latter feature corresponds to smooth muscle hypertrophy around the islands of endometrium, a finding that, when present, can help distinguish adenomyosis from an irregular endomyometrial junction on histologic examination.

Diagnostic criteria are somewhat controversial, mostly stemming from lack of agreement on how deep the focus must be in the myometrium for the process to be considered adenomyosis rather than an irregular endometrial-myometrial interface. Endometrial glands and stroma located in the myometrium at a depth of at least 25% of the overall thickness have been proposed; the location of glands and stroma one field (10X objective) beneath the endomyometrial junction has also been suggested.

The large pink stromal cells with pseudo-decidual change may be misconstrued as histiocytes and raise the possibility of a granulomatous process, particularly malacoplakia. Malacoplakia is a chronic inflammatory process associated with a variety of bacterial infections, most commonly enteropathic Escherichia coli. When involved, the distal female genital tract (vagina > cervix) is the most common site although it can occur in the endometrium, fallopian tube, and ovary. On gross examination, it typically appears as soft yellow nodules or plaques that microscopically correlate with sheets of histiocytes associated with intra- and extracellular targetoid inclusions (Michaelis-Gutman bodies); the latter are PAS-D and von Kossa positive.

Metastatic carcinoma may fall into the differential as the large pink pseudo-decidual stromal cells may mimic an infiltrative tumor around the glands. However, in adenomyosis, the stromal cells lack atypia, mitoses are scarce, and if stains are necessary, would be negative for keratins and positive for CD10.

Müllerian adenosarcoma may be considered, as the stroma surrounding the glands has a different morphologic appearance than the background endometrium and some of the glands have a slit-like configuration. However, in adenomyosis, a well-developed phyllodes-like architecture is lacking; there is no periglandular cuffing by hypercellular stroma, and the stromal cells appear bland with little to no mitotic activity.

Placental site trophoblastic tumor may be entertained as it is composed of cells with eosinophilic cytoplasm; however, it typically forms a well-circumscribed mass that may show hemorrhage and necrosis. It is composed of predominantly mononuclear cells with variable degrees of nuclear pleomorphism infiltrating between muscle bundles in sheets, nests, or cords, often with single cells at the periphery of the mass. In contrast to pseudo-decidua, the tumor cells are positive for low molecular weight cytokeratin, EMA, GATA3, and inhibin.

  1. Which of the following processes is typically associated with the uterine wall grossly appearing coarsely trabecular with multiple pinpoint hemorrhagic cysts?

    1. Adenomyosis
    2. Malacoplakia
    3. Metastatic carcinoma
    4. Müllerian adenosarcoma
    5. Placental site trophoblastic tumor
  2. Which of the following processes is associated with a variety of bacterial infections, most commonly enteropathic Escherichia coli?

    1. Adenomyosis
    2. Malacoplakia
    3. Metastatic carcinoma
    4. Müllerian adenosarcoma
    5. Placental site trophoblastic tumor
  3. Which of the following processes is composed of mononuclear cells with abundant eosinophilic cytoplasm that are positive for GATA3?

    1. Adenomyosis
    2. Malacoplakia
    3. Metastatic carcinoma
    4. Müllerian adenosarcoma
    5. Placental site trophoblastic tumor

References

  1. McCluggage WG, Robboy SJ. Mesenchymal uterine tumors, other than pure smooth muscle neoplasms, and adenomyosis. In: Robboy SJ, Mutter GL, Prat J, Bentley RC, Russell P, Anderson MC, eds. Robboy's Pathology of the Female Reproductive Tract, Second Edition. London, Eng: Churchill Livingstone Elsevier Limited; 2009:450-453.
  2. Meserve EE, Nucci MR. Malacoplakia. In: Diagnostic Pathology Gynecologic. London, Eng: Elsevier; 2014, 2:6-7.
  3. Mirkovic J, Elias K, Drapkin R, Barletta JA, Quade B, Hirsch MS. GATA 3 expression in gestational trophoblastic tumors. Histopathology. 2015;67:636-644.

Author

Marisa R. Nucci, MD
Surgical Pathology Committee
Brigham and Women’s Hospital
Boston, MA


Answer Key

  1. Adenomyosis (a)
  2. Malakoplakia (b)
  3. Placental site trophoblastic tumor (e)