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Background

The uterus and cervix form a continuous unit and in turn are attached to the fallopian tubes and ovaries.  The portion of the uterus which is lined by the endometrium is termed the uterine corpus.  The endometrium is the mucosal lining of the uterus which is shed monthly during menstruation.  It is also the site where the newly fertilized egg attaches and grows with a developing placenta.  Pathologists commonly receive biopsies from the endometrium, endocervix, and cervix.   

The menstrual cycle can be dated quite precisely by a pathologist. The following table illustrates some of the salient features. POD stands for post ovulation day. Ovulation usually occurs on day 14 of a 28 day cycle.

Atypical Polypoid Adenomyoma
Bicornuate Uterus-Gross Photo
Cervical Cancer (Cervical Dysplasia, CIN, Squamous Cell Carcinoma)
Cervical Cancer, Adenocarcinoma
Endometrial Cancer
Endometrial Hyperplasia
Endometrial Polyp
Endometrial Stromal Tumors
Malignant Mixed Mullerian Tumor (Carcinosarcoma, Sarcomatoid Carcinoma)
Pap Smear
Uterine Adenosarcoma
Uterine Leiomyoma (Fibroids)
Uterine Leiomyosarcoma
Uterine Serous Carcinoma

OUTLINE

Differential Diagnosis  
Histopathological Features and Variants  
Prognosis  
Treatment  
Commonly Used Terms  
Internet Links  

PROLIFERATIVE ENDOMETRIUM HISTOLOGIC FINDINGS
Early Straight glands
Mid Mid Coiled glands Stromal edema
Late Subnuclear vacuoles <50% of glands
SECRETORY ENDOMETRIUM  
EARLY Vacuolated glands
POD 2
Subnuclear vacuoles uniformly present >50% of glands
POD 3
Subnuclear vacuoles and nuclei uniformly aligned
POD 4
Vacuoles assume luminal position, MF rare
POD 5
Vacuoles uncommon, rare secretion
MID Stromal edema
POD 6
Secretion prominent
POD 7
Beginning stromal edema
POD 8
Maximal stromal edema
LATE

Stromal Predecidualization

POD 9
Spiral arteries first prominent
POD 10
Thick periarterial cuffs of predecidua
POD 11
Islands of predecidua in superficial compactum
POD 12
Beginning coalescence of islands of predecidua
POD 13
Confluence of surface islands, stromal granulocytes
POD 14
Extravasation of rbcs, prominent stromal granulocytes
MENSTRUAL ENDOMETRIUM Crumbling stroma
Intravascular fibrin thrombi
Stromal granulocytes
PMNs prominent
Late menstrual
Regenerative changes prominent

 

HISTOPATHOLOGICAL VARIANTS CHARACTERIZATION
GENERAL  


Number of levels needed for diagnosis of cervical biopsies.

Vivian Luo Y, Prihoda TJ, Sharkey FE.

Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, Tex.

Arch Pathol Lab Med 2002 Oct;126(10):1205-8 Abstract quote

Context.-Three levels of histologic sections are routinely prepared for small biopsies in many surgical pathology laboratories. The first level is superficial and may not be representative of the entire biopsy, and may therefore represent wasted resources and time for technologists and pathologists alike.

Objective.-To determine if disposing of the first of 3 standard levels materially affects the diagnosis of cervical biopsies.

Design.-We retrospectively reviewed levels 2 and 3 of 241 cervical biopsies and compared the review diagnosis with the original diagnosis, using 6 diagnostic categories: I, benign lesions; II, human papillomavirus-associated changes or low-grade dysplasia; III, high-grade dysplasia/carcinoma in situ; IV, invasive carcinoma; V, insufficient tissue for diagnosis; and VI, further workup needed. If there was a discrepancy between the original and review diagnostic categories, then we examined level 1 to determine if this would resolve the disagreement. Setting.-The surgical pathology laboratory.

Patients.-Women undergoing cervical biopsy. Interventions.-None.

Main Outcome Measures.-The frequency with which level 1 information changed the diagnostic category determined with levels 2 and 3 only. Results.-After review of levels 2 and 3, the diagnosis in 42 (17%) of 241 cases was in disagreement with the original diagnosis. Upon review of level 1, the review category was changed to that of the original diagnosis in only one case.

Conclusions.-The first of 3 levels contributed little to reaching a diagnosis in these cervical biopsies. Control of interobserver variation would seem to be superior to preparation of additional levels as a strategy for reducing diagnostic error.

VARIANTS  
CALCIFICATIONS  

The significance of psammoma bodies that are found incidentally during endometrial biopsy.

Fausett MB, Zahn CM, Kendall BS, Barth WH Jr.

Department of Obstetrics and Gynecology, Keesler AFB Hospital, MS, USA.
Am J Obstet Gynecol. 2002 Feb;186(2):180-3. Abstract quote

OBJECTIVE: The purpose of this study was to elucidate the significance of psammoma bodies that are found incidentally during endometrial biopsy.

STUDY DESIGN: We reviewed the medical records of 11 women who were found to have psammoma bodies during endometrial biopsy over an 18-month period and extracted data that included demographic information, extent of evaluation, and pathologic findings.

RESULTS: Ten women were postmenopausal and underwent endometrial biopsy for abnormal uterine bleeding while using combined hormone replacement. Most women underwent dilation and curettage with hysteroscopy plus either laparoscopy or ultrasonography. Notable findings included: 5 women with endometrial polyps, 2 women with endometriosis, 1 woman with endosalpingiosis, and 1 woman with a mature cystic teratoma. No endometrial or adnexal malignancies were identified.

CONCLUSION: This series represents the largest series to date regarding psammoma bodies that have been found incidentally during endometrial biopsy. All psammoma bodies were associated with benign findings. Further evaluation of the endometrial cavity with hysteroscopy or sonohysterography, plus some form of adnexal assessment, is a reasonable definitive evaluation scheme.


Calcifications in ovary and endometrium and their neoplasms.

Silva EG, Deavers MT, Parlow AF, Gershenson DM, Malpica A.

Departments of Pathology (EGS, AM, MTD) and Gynecologic Oncology (DMG), The University of Texas M. D. Anderson Cancer Center, Houston, Texas.


Mod Pathol 2003 Mar;16(3):219-22 Abstract quote

In this study, we investigated the role of hormones in the pathogenesis of calcifications in ovary and in endometrium and their neoplasms of the gynecologic tract and assessed the anatomic location and incidence of these calcifications.

The study consists of three parts designed to investigate the pathogenesis, the location, and the incidence of calcifications in ovary and endometrium and their neoplasms. In the first part, 79 female guinea pigs were divided into 10 groups, and different hormones, given weekly for 12 months, were administered to the guinea pigs by group. A control group of 7 guinea pigs received sterile water. Calcifications developed in 5 of 7 guinea pigs treated with prolactin, 10 of 20 treated with human chorionic gonadotropin, 5 of 11 treated with estradiol, 3 of 7 treated with estrone, 1 of 6 treated with growth hormone, and 1 of 10 treated with testosterone; in 20 of the guinea pigs, the calcifications developed in the stroma of the endometrium, and in 5 guinea pigs, they developed in the ovary. The second part of the study consisted of an evaluation of the specific location of calcifications in 43 consecutive human surgical ovaries and endometria. Calcifications were seen only in the stroma in 100% of the ovarian serous adenofibroma specimens; in ovarian serous borderline neoplasms, the stroma contained 70 to 100% of the calcifications, and the epithelium had 0 to 30% of the calcifications. In ovarian serous carcinoma specimens, the calcifications were seen in the stroma in 50 to 60% of the cases, in the epithelium in 40% of the cases, and in areas of necrosis in 10% of the cases. The third part of the study was directed to determine the frequency of calcifications in ovarian lesions.

We found that all cases of endosalpingiosis and ovarian low-grade serous carcinoma had calcifications, whereas 80% of the cases of serous borderline tumor had calcifications, and only 50% of the cases of ovarian high-grade serous carcinoma contained calcifications.

The results of this study indicate that the majority of the calcifications in the ovary and the endometrium and their neoplasms are present in the stroma.

This is most probably secondary to metabolic changes, which could be related to hormones and not caused by degenerative changes in epithelial cells.

ENDOMETRITIS, PNEUMOPOLYCYSTIC  
Pneumopolycystic Endometritis.

Val-Bernal JF, Villoria F, Cagigal ML, Bretones JM.

From the Departments of *Anatomic Pathology and daggerObstetrics and Gynecology, Marques de Valdecilla University Hospital, Medical Faculty, University of Cantabria, Santander, Spain.

Am J Surg Pathol. 2006 Feb;30(2):258-261. Abstract quote  

Emphysematous inflammations of the abdomen and pelvis are uncommon and potentially life-threatening conditions that require aggressive treatment. Pneumopolycystic endometritis is a rare benign condition of which only 1 case has been described.

This report describes the sonographic and histologic appearance of pneumopolycystic endometritis in a 49-year-old woman who presented with irregular menses and hypermenorrhea of 1 year's duration. The entity is characterized by gas-filled cysts in the endometrium stroma, in a pattern similar to pneumatosis of the vagina. The histologic picture is specific and should not be confused with gas gangrene involving the uterus characterized by the presence of tissue necrosis and life-threatening infection.

Our patient is the first documented case that occurred spontaneously and at the same time was limited to the endometrium. Recognition of pneumopolycystic endometritis is important because this condition does not represent an aggressive life-threatening infection, and spontaneous resolution is to be expected.
GRANULOMAS  
Uterine Granulomas
Clinical and Pathologic Features


Mohammad O. Almoujahed, MD
Laurence E. Briski, MD
Michael Prysak, PhD, MD
Leonard B. Johnson, MD
Riad Khatib, MD

Am J Clin Pathol 2002;117:771-775 Abstract quote

We retrospectively studied the clinical and pathologic features of uterine granulomas over a 10-year period. Granulomas were detected in 30 women, 22 to 81 years old, in the cervix (n = 12/1,090 cervical specimens; 1.1%) or uterine corpus (n = 18/12,000 uterine specimens; 0.15%). They were discovered during evaluation of abnormal bleeding, cytologic specimens, or other gynecologic conditions. None of the patients had constitutional symptoms. These granulomas were often focal (n = 25 [83%]), exhibiting features of foreign body–type (n = 17 [68%]); or they were diffuse (n = 5 [17%]), all with negative acid-fast bacilli or fungal stains and sometimes necrotizing (2 [40%]). Focal granulomas were highly associated with a preceding biopsy or surgery (22/25 vs 14/53 age-matched control subjects). Follow-up of 28 patients (median, 16 months) showed that 27 remained healthy; only 1 patient developed generalized lesions consistent with sarcoidosis 16 months later.

Uterine granulomas are rare. They are either focal, related to previous biopsy or surgery, or diffuse, usually representing local reaction without an obvious cause. Association with infection or systemic granulomatous disorders is uncommon.

NODULAR HISTIOCYTIC HYPERPLASIA  
Nodular Histiocytic Hyperplasia of the Endometrium

Kyu-Rae Kim, M.D.; Yong Hee Lee, M.D.; Jae Y. Ro, M.D.

From the Department of Diagnostic Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (K.-R.K., J.Y.R), and Bundang Hospital, College of Medicine Pochon Cha University, Kyounggi-do, Korea (Y.H.L.).

Int J Gynecol Pathol 2002;21:141-146 Abstract quote

We describe the clinical and pathologic features of four cases of nodular histiocytic proliferation in the endometrium. We have been able to find only one brief reference to this lesion in the literature.

The lesion in each case was a detached nodule composed of aggregates of histiocytes within a biopsy or curettage specimen. The constituent cells differed from foamy histiocytes of the endometrium in that they had either lobulated or ovoid, vesicular nuclei, distinctive cytoplasmic margins, and a moderate amount of amphophilic cytoplasm. Mitoses were frequent (up to 11 per 10 high-power fields) in one case but were absent in the remaining cases. On immunohistochemical staining, CD68 and lysozyme were strongly expressed in the cytoplasm. Neither estrogen receptor nor progesterone receptor was expressed in contrast to the background endometrium. The cells were also negative for S-100 and cytokeratin. Each patient's postcurettage course was uneventful. The cause of nodular histiocytic proliferation of the endometrium is currently unknown, although response to intracavitary debris has been suggested.

The lesion should not be confused with a variety of reactive, inflammatory, or neoplastic conditions, such as xanthogranulomatous endometritis, malakoplakia, histiocytic granuloma, hormonal changes of the endometrial stroma, Langerhans' cell histiocytosis, morular metaplasia, extravillous trophoblast, or exaggerated placental site reaction.

PROSTATE TISSUE, ECTOPIC  
Ectopic Prostatic Tissue in the Uterine Cervix and Vagina: Report of a Series With a Detailed Immunohistochemical Analysis.

McCluggage WG, Ganesan R, Hirschowitz L, Miller K, Rollason TP.

From the *Department of Pathology, Royal Group of Hospitals Trust, Belfast, U.K.; daggerDepartment of Pathology, Birmingham Women's Hospital, Birmingham, U.K.; double daggerDepartment of Cellular Pathology, Royal United Hospital, Bath, U.K.; and section signDepartment of Pathology, University College Hospital, London, U.K.


Am J Surg Pathol. 2006 Feb;30(2):209-215. Abstract quote  

Prostatic tissue has rarely been described in the lower female genital tract.

We describe 6 cases of ectopic prostatic tissue: 5 involving the cervix and 1 the vagina. The latter is the first reported example of benign prostatic tissue in the vagina. The age of the patients ranged from 21 to 65 years; and in all cases, the prostatic tissue was located within the cervical or vaginal stroma without involvement of the surface. In all cases, there were both glandular and squamous elements, which varied in prominence. In some cases, the squamous elements predominated to such an extent that the underlying glandular component was easily overlooked. In the glandular areas, a double cell layer of luminal and basal cells was focally apparent. There was little cytologic atypia or mitotic activity.

Immunohistochemically, 3 of 6 cases were positive with prostate specific antigen (PSA) and all 6 cases marked with prostatic acid phosphatase (PSAP). In some of the positive cases, staining was focal. Positive staining with prostatic markers was confined to the glandular elements with no staining of the squamous areas. Immunohistochemical staining with the high molecular weight cytokeratin 34betaE12 highlighted the basal cell layer, which often extended into the center of the cellular islands, reminiscent of basal cell hyperplasia involving the prostate gland. All cases tested were CD10 positive (largely restricted to the basal cell layer), alpha-methylacyl-CoA racemase positive, and p16 negative. Estrogen receptor (ER) and progesterone receptor (PR) were negative in the glandular areas, but ER was positive in the squamous elements in all cases and PR was positive in 1 case. All cases tested were androgen receptor positive and exhibited a low MIB-1 proliferation index with only scattered positive nuclei.

The presence of ectopic prostatic tissue in the lower female genital tract may be more common than is appreciated. Once the possibility is considered, the diagnosis is easily confirmed using immunohistochemistry, although staining with prostatic markers may be focal and PSA may be negative. Ectopic prostatic tissue in the lower female genital tract is almost certainly a benign condition, based on the morphology, including the presence of a double cell layer, although follow-up of larger numbers of cases is required.

Possible theories of histogenesis include a developmental anomaly, metaplasia of preexisting endocervical glands, and derivation from mesonephric remnants.
VASCULAR CHANGES  
Vessels Within Vessels in the Myometrium

S. Merchant, M.D. ; A. Malpica, M.D. ; M. T. Deavers, M.D. ; C. Czapar, M.D. ; D. Gershenson, M.D. ; E. G. Silva, M.D.

From the Departments of Pathology (S.M., A.M., M.T.D., E.G.S.) and Gynecologic Oncology (D.G.), University of Texas M.D. Anderson Cancer Center, Houston, Texas; and the Department of Pathology (C.C.), Mt. Sinai Hospital, Chicago, Illinois, U.S.A.

Am J Surg Pathol 2002;26:232-236 Abstract quote

We have encountered a peculiar vascular architecture in the myometrium wherein arteries are found free-floating within cleft-like spaces.

Using different colored dye injections in the uterine arteries and veins, we demonstrated that these spaces are venous channels. This was confirmed by immunoperoxidase staining for CD34, which enhanced the cells lining these spaces.

A review of 81 hysterectomy specimens showed that this vascular architecture was present in 42 cases (52%), while it was identified in the parenchyma of only two mastectomy specimens among the 45 specimens from different organs studied. A strong association existed between the presence of this architecture and history of menorrhagia (p = 0.0116).

This peculiar vascular architecture might be important in the pathogenesis of menorrhagia and the development of intravenous leiomyomatosis. Pathologists should also be able to recognize these spaces as vascular channels in the event that malignant cells are identified within them.

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Commonly Used Terms

Hysterectomy-Surgical procedure which removes the uterus.  If the cervix is removed with the uterine corpus, it is termed a total hysterectomy.  If the cervix is not removed, it is called a supracervical hysterectomy.  If the ovaries and uterine tubes are also removed, it is called a total hysterectomy with bilateral salpingo-oophorectomy.  If the procedure is performed with an incision through the abdomen, it is called a total abdominal hysterectomy.  If the removal occurs through the vagina, it is called a vaginal hysterectomy

Nabothian Cysts-These are small cysts which occur in the endocervix and formed by retention of mucous produced by small glands located below the surface of the mucosa.  They are benign and considered part of the normal cervix.

Subnuclear Vacuoles-These are spaces located below the nuclei of the endometrial glands.  When present, it is consistent with the early secretory phase of the menstrual cycle.

Basic Principles of Disease
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Commonly Used Terms
This is a glossary of terms often found in a pathology report.

Diagnostic Process
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Surgical Pathology Report
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How Accurate is My Report?
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Got Path?
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Last Updated February 14, 2006

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