The Pathology Reproductive

Teaching Monograph The Pathology of the Female Reproductive Tract John M. Craig, MD Boston Hospital for Women Harvard Medical School Boston, Massachusetts Copyright 0 1979, Universities Associated for Research and Education in Pathology, Inc. All rights reserved The American Journal of Pathology Official publication of The American Association of Pathologists Published by The American Association of Pathologists, 9650 Rockville Pike, Bethesda, Maryland The Patholo of the Female Reproductive Tract Vulva 385(1 Cervix 391(7) Endometnum 400 16) Myoumeium 408(24 Fallpian Tubes 411(274) Ovay 415I31) The Patholo of Pregnancy 429(45) Malf ains of the Placenta 430(46) Circulating Disorders of the Plcenta *32(48) Infecims of the Plaxcet 43:3 49) Placental Pathology Associated With Maternal Disease 434 50) Tumors of the Placenta 4:35(51) Foreword to Teaching Monographs This teaching monograph is being published by The American Journal of Pathol- ogy for Universities Associated for Research and Education in Pathology as a service to medical students and their teachers of pathology. This venture repre- sents a joint effort to make such teaching material available to a wide audience. Separately bound copies of this Teaching Monograph can be purchased from Universities Associated for Research and Education in Pathology, Inc., 9650 Rockville Pike, Bethesda, MD 20014. The charge is $2.25 per copy for orders of up to ten and $1.25 per copy for orders of ten or more (prepaid). The Editorial Board John R. Carter, MD, Case Western Reserve University School of Medicine Francis E. Cuppage, MD, University of Kansas Medical Center Joe W. Grisham, MD, The University of North Carolina School of Medicine Robert B. Jennings, MD, Duke University Medical School Werner H. Kirsten, MD, The University of Chicago Vincent R. Marchesi, MD, Yale University School of Medicine Goetz W. Richter, MD, The University of Rochester School of Medicine Dante G. Scarpelli, MD, Northwestern University Medical School Robert E. Stowell, MD, University of California, Davis Benjamin F. Trump, MD, University of Maryland Series Editor: Dante G. Scarpelli, MD The Pathology of the Female Reproductive Tract John M. Craig, MD Vulva The vulva, covered by epidermis, is subject to most of the infections and reactive processes of the remaining coverings of the body. In addition, however, because of its reactivitv to the local levels of estrogen and because of the special adnexal structures and arrangements, the exposure to venereally acquired pathogens and to vaginal and urethral discharges, it has its own unique pathology. It is at the extremes of life that estrogen lack can play an etiologic role in vulvar pathology. In voung children, the nonestrogenicall.v stimulated thin epithelium is susceptible to attack bv gonococci, giving rise to acute vulvovaginitis, an acute edematous lesion with a marked polvmorphonu- clear reaction. This mav be quickly relieved by the application of estrogen. In very old women, the lack of estrogens causes atrophv not only of the epidermis but also the adnexal gland structures and subcutaneous fat, so that a generalized atrophy occurs: a condition labeled "'kraurosis.'" This process, with the attendant atvpical epidermal and dermal reactions that accompanv it in varving degrees, have been labeled more recentlv "vulvar dvstrophv." The markedlv thinned vulvar skin may be the site of infection or ulceration. The skin reacting to the infection may become acanthotic and hvperkeratotic; in the latter instance, gross white patches can be identified clinicallv (so-called leukoplakia). Other histologic forms of dvstrophv include scaling of lichenification, sclerosis and hvalinization of the papillary dermis, and flattening of the rete pegs. The reactive state in the dvstrophic vulva is not static: a hypertrophic area with thickening and elongation of the rete pegs and hyperkeratosis with varving degrees of inflammation of the dermis may be seen in the same patient as areas of atrophv. Such variations are induced by irritating discharges, chronic infection, and trauma induced by scratching. Aside from the nonspecific infections mentioned above, the common specific infections of the vulva are venereal and mvcotic. The ulcer of syphilis, with its firm, elevated, painless, round edge and central ulceration, shows on microscopic examination a marked papillary hvperplasia of the epithelium with an intense plasma cell infiltration in the dermis accompanied by a marked increase in capillarv net to form a gran- ulomatous lesion. The femoral and inguinal lymph nodes will be enlarged if the infection is more than 2 to 3 weeks in duration. The second venerally acquired disease that gives rise to lesions of the vulva is herpes genitalis. This causes shallow, painful, ervthematous ulcer- 0002-9440/79/0208-0381$01.00 385(1) 0 1979 UAREP 386(2) CRAIG American Journal of Pathology ation, occasionally with small peripheral vesicles. The inflammation is intense, with lymphocytes and mononuclear cells in the dermis. The distinguishing feature is the presence of intranuclear inclusions in bal- looned nuclei of the squamous epithelium, often as syncitial giant cells in the vesicles at the borders of the lesions. The third common, although nonvenereal, specific infection is monilial. This is primarily seen in diabetic patients, in whom a combination of high tissue and urine glucose levels give rise to a favorable fungal culture media. The vulva is erythematous, with elevated white patches which can be partially scraped away. The Candida organisms grow on but may invade the superficial layers of the desquamating epidermis. The under- lying dermis shows a nonspecific lymphocytic and monocytic response. Of the infections of the adnexal structures, acute infection of Bartho- lin's gland lying just at the lateral border of the vulva and vagina leads commonly to duct obstruction and subsequent dilatation and infection of the squamous-cell-lined ducts. The thinned epithelium of the duct may be eroded and replaced by a subacute inflammatory reaction. There is usually little or no involvement of the mucus-secreting glandular ele- ments. Of the benign tumorous growths in the vulvar area, there are two which are relatively common and special to this area. The first of these is a venereally acquired epithelial overgrowth of viral etiology, ie, condyloma acuminata. Similar lesions occur in the vagina and cervix and under the foreskin in the male. These warty papillary growths are often multicentric and, in rare cases, cover much of the vulvar and perianal skin. They consist of acanthotic epidermal overgrowths, with a regular maturational progression from the basal layers to the surface. The cells contain little glycogen. They may keratinize just before desquamation, but hyperkeratosis is not common. The papillae of the dermis are narrowed and contain few inflammatory cells. The margins of the lesions are sharply demarcated, and there is little "field change" in the adjacent epidermis. No inclusion bodies are present, although perinuclear halos can be found. Mitoses are limited to the basal layer. These lesions occasionally may be confused with squamous papillomata. The second benign tumor of the vulvar area, rarely seen elsewhere in the skin, is an adenoma of the apocrine gland, ie, the hidradenoma. These form small circumscribed masses in the labia. Microscopically, they are usually well-circumscribed by a pseudocapsule and are composed of very thin papillary fronds covered by a single layer of cuboidal cells. The tumors are slowly growing and do not contain mitoses. The vulva, like the cervix, appears to undergo malignant degeneration Vd. 94, No. 2 PATHOLOGY OF FEMALE REPRODUCTIVE TRACT 387(3) February 1979 over a long time; premalignant changes may be fairly widespread before invasion occurs. Such degeneration is chieflv seen in older women and may accompany the vulvar dystrophies mentioned previously. The lesions progress through hyperkeratotic acanthotic changes in the epidermis with varying degrees of dysplasia to carcinoma in situ. The dysplasias are characterized by the presence of immature cells, at first confined to the lower third of the epidermis but, with more severe lesions, atvpical basal cells having large hyperchromatic nuclei and reduced cytoplasm extend up to one half of the thickness of the epidermis, and finally the entire thickness of the epithelium is replaced by dysplastic atypical basal cells with verv scant cytoplasm and very granular hyperplastic nuclei. The latter stage can then be labeled "intra epithelial carcinoma" or "carcinoma-in-situ." Such lesions may be limited in extent or may rarelv extend widely over the vulva. Because of the hyperkeratotic surface layer, they will appear as white patches grosslv, hence the term "leukoplakia," but the same hyperkeratosis may be present without malignant alterations so that the term should be used only descriptively. Because of the non- tumorous growth characteristics, the determination of the extent of the lesion is often dependent on multiple biopsy specimens. Invasive squamous carcinoma forms one end of a continuous spectrum with those of earlv dysplasias. It has the varied histologic equivalents of squamous carcinoma of the skin, but again the vulva has unique characteristics. Here squamous carcinoma is distinguished by its rapid spread to adjacent lymph nodes and by its poor prognosis. The latter is influenced by the size of the lesion, by the grade of histologic differentiation, by the depth of the invasion of the local lesion (Levels I through IV), and most stronglv bv the clinical stage (Stage I, less than 2.0 cm in diameter and confined to the vulva; Stage II, confined to the vulva and over 2.0 cm in diameter; Stage III, suspicious involvement of the groin nodes; Stage IV, grosslv positive groin nodes or other metastases). Stages I and II have 90% 5-year survivals, and Stage III has less than 25%, with an overall survival for all stages of a little more than 50%. The poor survival is related to diagnostic delay largely due to patient factors.

Load more