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Friday February 23, 2001, 11a, P022311 Pathology- Dr Mira Scribe: Steve Hewitt Proof: Tony Cauchi Pathology of Female Genital Tract Scribe note: Well, the good news is that we are done with the Translation part of the course. The bad, however, is that we’re not out of the woods yet. After scribing this lecture I felt like unwinding by watching Sabado Gigante on Univision, or at least Robert Rodriguez’s Sundance favorite El Mariachi, or maybe something by Pedro Almodovar. That said, Dr M started with Vulvar Cysts on page 365 of the notes. The numbers that appear accompanying the slide headings refer to his power point presentation on the web. http://www.macmed.ttuhsc.edu/Mira/gynecologic/index.htm Vulvar Cysts o Most vulvar cysts are benign. o Epidermal inclusion cysts are some of the most common cysts in the vulvar region. They are usually secondary to trauma, i.e. child delivery or surgery done during delivery. Manifest as subq lesions that involve the labia majora or minora. Frequently seen in areas where an episiotomy has been performed, especially in multiparous women. Also seen in posterior fornix secondary to lacerations during delivery. Slide- histo (photo 46-47): Cyst is lined by squamous epithelium and filled with abundant keratinous debris, NOT sebum. This debris resembles sebum, however, and these cysts are known clinically as sebaceous cysts. Slide (Photo 46-47): Dermal cyst with adnexal structures below the squamous epithelium. In an epidermal cyst, however, there are no skin adnexa associated with the lesion. o Bartholin’s cysts are frequently secondary to inflammation of Bartholin’s glands- Bartholinitis, abscesses. Can occur at any age, and reach a size of 3-5 cm. Inflammation causes glandular secretions to accumulate within the lumen of the duct. Therefore, this is a cyst of the duct, NOT a cyst of the gland itself. Can be excised or marsupialized (incision the cyst and invagination of the flaps of the cyst to allow drainage). Slide-gross (48): Bartholin’s cyst, as opposed to B’s abscess, involves no inflammation of the surrounding skin. It is usually located in the vestibulum (posterolateral aspect of introitus). Slide-histo (49): This is a cyst of the duct so it is lined by the transitional epithelium of the duct. Frequently you see some transformation to squamous epithelium due to metaplasia. Thus, you can see transitional or squamous epithelium, or both, depending on the degree of squamous metaplasia present. Slide- histo (50): At high power, epithelium is similar to that of bladder or ureter. The superficial cells are large, with large amount of cytoplasm, while those at bottom are smaller with less cytoplasm. o Mucous cysts arise from vestibular glands in the vulva and from the paraurethral (Skene’s) glands. These are mucus glands, so the epithelium will stain for mucin using mucicarmin or alcian blue. Importantly, you will NOT see myoepithelial cells or smooth muscle underneath the wall of the cyst. This is important to distinguish these cysts from others that may have mucin content. Slide-gross (52): located in same area as Bartholin’s glands Slide- histo (53): lined with columnar mucinous epithelium without visible nuclei at the base of the epithelium. Cytoplasm is filled with mucopolysaccharide, so PAS will stain the cell pink. There are no myoepithelial cells or muscle present below the epithelium. Miscellaneous Benign Vulvar Lesions o Ectopic breast tissue- can be seen in vulva. The glands in the vulva are essentially like those in the breast, having the same embryologic origin. The vulvar glands can develop functional activity similar to those in the breast. Slide-gross (55): soft, protruding mass of ectopic breast tissue on internal aspect of labia majora. This mass can actually lactate during pregnancy. Keep in mind that any cyst that occurs in the breast can also occur in ectopic breast tissue in the vulva- cancer, fibroadenomas, and fibrocystic changes. o Molluscum contagiosum- is caused by a poxvirus and is an STD; characterized by papules on the skin with central umbilication where most of the viral inclusions are located. Can occur anywhere on the body; it’s an STD so contact with an infected part of the body will produce the characteristic lesions. Slide-gross (57): lesions with central umbilicated area full of keratin debris and cells containing molluscum bodies, which are viral inclusion bodies. The lesion will not infiltrate the dermis so it is not a tumah Slide- histo (58): papillomatous proliferation with hyperkeratosis. Slide- histo (59): large pink inclusion bodies “in bottom layer of skin”= molluscum bodies. o Vestibular adenitis- unknown etiology, but “it’s a very annoying” inflammation of the vestibular glands in the posterior introitus. It’s a very painful process that frequently ends up as ulcerations of the introitus. Excision of the offending glands is the best treatment. o Soft tissue tumors- there are many types that you see in other parts of the body that you also can see in the vulva- lipomas, leiomyomas. The following tumors are found more commonly in the vulva than elsewhere (although granular cell tumors are an exception). Granular cell tumors have been described in practically every organ and tissue in the body. Cellular angiofibromas can be confused with sarcomas. Aggressive angiomyxoma and angiomyofibroblastoma are very characteristic of the vulva, especially angiomyxoma because it can infiltrate into the vulvar and perivulvar soft tissues. Slide- gross (60): This is how most soft tissue tumors will present- not exactly within the vulva but outside in the labia majora or perineal/gluteal areas. Usually a subq tumor that protrudes through the skin. This one is a lipoma. Angiomyofibroblastomas should be remembered in differential dx for soft tissue tumors. These are usually well circumscribed, and histologically similar to aggressive angiomyxomas. They differ in that angiomyxomas have infiltrative margins Slide- histo (62): Aggressive angiomyxoma has hypocellular stroma, large vessels with thick walls, and proliferative myofibroblasts that infiltrate the surrounding tissue. This is a very aggressive, locally invasive and destructive lesion, but it doesn’t metastasize. Angiomyofibroblastomas have alternating areas of hypo- and hypercellularity, and the vessels tend to be more capillary-like with thinner walls. Both of these lesions are important to know in vulvar soft tissue tumor pathology. Skin tags and nevi are common. Papillary Hidradenoma o The counterpart to the ductal papilloma of the breast because they are histologically similar. o Well-circumscribed tumor margins. Characterized by papillary proliferation of epithelium within the gland. o Slide-gross (64-65): large nodules in the skin of the labia majora, or more commonly as umbilicated lesions that can be confused with cancer or other inflammatory disease of the vulva that produce ulcers or nodules with central umbilication. o Slide-histo (66-67): again, similar to papilloma of the breast. Complex papillary proliferation that “fills up the gland.” Usually the epithelium of these lesions is a double layer of epithelial cellscells on the surface are more columnar/cuboidal with round nuclei usually located at the base of the cell, with myoepithelial cells at the bottom of the double layer. o Staining with mucicarmin will yield a positive result because these tumors produce mucus. Vulvar Dystrophy o This is an umbrella term for lichen sclerosus and squamous hyperplasia. These lesions can coexist simultaneously. They are NOT premalignant lesions, but 10 % of squamous cell carcinomas of the vulva actually develop in association with squamous hyperplasia or lichen sclerosus. Additionally, both of these lesions can be accompanied by vulvar intraepithelial neoplasias (VIN) (see below) or vulvar dysplasias. o Lichen sclerosus (previously known as lichen sclerosus atrophicus) can occur at any age (newborn to postmenopausal women), but it is most common in postmenopausal women. Characterized by thinning of the epidermis and loss of rete pegs, with dermal fibrosis and chronic “lichenoid” inflammation- the inflammatory cells infiltrate underneath the dermis. Patients tend to scratch these lesions, leading to hemorrhage and infection Slide- gross (69-70): (Robbins p 1041, 24-6) skin of vulva if white, shiny and smooth, and its elasticity is lost. The skin is thin and “stretched out,” so introitus can be practically obliterated. Lichen sclerosus can involve part or the entire vulva, including clitoris, labia minora, and perineal/perianal skin. Disease can progress to destruction of entire labia minora/majora Slide-histo (71): (p 1041, 24-7) similar findings in both male and female. Hyperkeratotic skin with “big fat” layer of keratin on top of epidermis. Rete pegs and ridges are lost so no papillae are evident underneath the skin- the skin is flat. Dermis is frequently edematous and sclerotic Sometimes the capillaries of the skin dilate, allowing the “lichenoid infiltration” underneath the lesion. Therefore, although the skin is thinning, it is still metabolically active (meaning that there is no atrophy, which is why “atrophicus” was dropped from the disease name). There is usually no cellular atypia, but some can become dysplastic- thus don’t forget the possibility of cancer in evaluation of lichen sclerosus. o Squamous hyperplasia, previously known as hyperplastic dystrophy. Slide- gross (72): a much thicker, more leathery lesion (as opposed to lichen’s thin, white lesion) that involves most of the vulvar skin. Slide-histo (73): (p 1042, 24-8) There is a very prominent hyperkeratinocytic hyperplasia with long papillae/rete pegs. There is a “lichenoid” inflammatory infiltrate at the bottom. In general, there will be a large thick layer of keratin under surface of skin. These lesions can be mixed with lichen sclerosus. Vulvar Intraepithelial Neoplasia (VIN) o This is a precancerous lesion. The dysplasia seen is graded as mild, moderate or severe (VIN IIII), as well as carcinoma in situ. o Associated with high-risk HPV types 16, 18 and some of the 30 group (last year’s scribe says 30 and 40 as well). These lesions can have many different types of clinical presentations. o Slide-gross (B1): multiple hyperpigmented skin lesions of variable size with irregular borders. This could be a melanocytic lesion OR carcinoma in situ. o Slide-gross (B2): multiple white plaques/ leukoplakias covering labia majora. o Leukoplakia is a clinical term that indicates a white plaque covering the vulvar skin. It does not describe the underlying pathology of the lesion. All these lesions have hyperkeratosis, which is why they look white, but underneath they can be inflammatory OR neoplastic. Therefore, ALWAYS BIOPSY any leukoplakia in any woman at any age in order to dx any cancer present. o Slide-gross (B3-B4-B5): Carcinoma in situ of the vulva can present as a hyperpigmented lesion involving practically all the vulvar skin- labia majora/minora, clitoris. Lesions can be papular and diffuse. o Slide-histo (B6-B7): (p 1043, 24-10) dx of VIN depends on degree of proliferation of dysplastic cells into the squamous epithelium. Mild dysplasia usually involves the inner third of the epithelium, moderate extends into the “middle” of the epithelium, and “anything after that” (i.e., involving the full thickness of the epithelium) is severe dysplasia or carcinoma in situ. The cells of carcinoma in situ are very large, with very little cytoplasm and hyperchromatic nuclei with intense mitotic activity. o Mitotic figures in the vulva are normally only seen in the basal cell layer; any mitosis outside of this layer is abnormal and indicates dysplasia. Squamous Cell Carcinoma (SCC) of the Vulva o May appear as leukoplakia so you must biopsy. ALL leukoplakias need to be biopsied. o Prognosis of SCC depends mostly on depth of invasion, which is measured by biopsy. The deeper the invasion, the greater the likelihood of metastatic disease to regional lymph nodes. o Verrucous carcinoma is a type of SCC that has very good prognosis because it does not infiltrate and therefore doesn’t involve lymphatics, making risk of metastasis very low. o Slide-gross (B9, but not benign, B10): SCC usually presents as large, ulcerating lesions that aren’t distinguishable from other inflammatory diseases. Usually has necrotic borders, and lesion o o o o o o can become infected and covered with a purulent exudate. Thus, inflammatory conditions are always in the differential dx of cancer, and cancer is always in the diff dx for inflammatory conditions of the vulva. Can involve labia majora/minora, clitoris. Slide-gross (B11): SCC has destroyed right side of labia majora and clitoris. Slide-histo (B12): no different than SCC anywhere else. Tongues of squamous cells infiltrating the stroma. Slide-histo (B12): Sometimes the cells of SCC do not look extremely malignant. Cells in center have abundant eosinophilic cytoplasm. Cells at periphery look more malignant, with more mitosis. An infiltrative border indicates SCC, whereas a smooth border will indicate verrucous carcinoma. So, no matter how well-differentiated the squamous epithelium, if you see an infiltrative margin, then you’re looking at SCC. Slide-histo (B13): Verrucous carcinoma has a very smooth border; it pushes against the dermis rather than infiltrating. Can be difficult to differentiate from condyloma acuminatum Slide-chart (B14): Illustrates how prognosis/depth of invasion relates to metastatic disease. Lesions that are a cm or less have low chance of metastasis. Deeper lesions (2-3 cm) have about a 12% chance of mets. 5 cm lesions have a 50% chance of mets. This is important because survival rate for vulvar cancer drops tremendously when mets to regional lymph nodes occur. Patients with SCC without mets have a 90-95% 5 year survival rate, but when mets occur survival rates drop to 10-20%. Depth of invasion (Slide B15) is measured from the tip of the rete pegs/papillae adjacent to the tumor down to the deepest portion of the tumor. Can also be measured from skin surface, but this will only allow measurement of the thickness of the tumor, not its maximal depth of invasion.