Primary Vulvar Adenocarcinoma of Cloacogenic Origin.

ABSTRACT: A 43-year-old woman who had a vulvar mass associated with mild discomfort was found to have a rare primary vulvar adenocarcinoma of probable cloacal origin. The tumor was contiguous with the surface epithelium of the vulva and was a well to moderately differentiated adenocarcinoma of colonic type. Stains of the neoplastic cells were positive for both acid and neutral mucin, and periodic acid-Schiff (PAS) was positive after diastase reaction. The neoplastic cells were strongly positive for carcinoembryonic antigen, broad spectrum cytokeratin, and p-53 antigen. Clinical evaluation failed to show any primary tumor in colon, lung, or breast. The patient was disease free 18 months after operation.

PRIMARY ADENOCARCINOMAS of the vulva are rare neoplasms. [1,2] The majority of cases reported in the literature arise from Bartholin's glands.'-3 In a few reported cases, origin from sweat glands, urethra, Skene's glands, ectopic mammary glands, and cloacal remnants has been suggested. [1,2] In a search of the literature dating back to 1959, we found fewer than 10 cases of vulvar adenocarcinoma originating within cloacal remnants. [46]

CASE REPORT

A 43-year-old African American woman (gravida 4, para 3, aborta 1) had a 2-month history of vulvar discomfort and bleeding. Physical examination revealed a 4 x 5 cm area of excoriation and erythema just posterior to the fourchette. No other lesions of the vulva, vagina, rectum, or perineum were found. Examination of the abdomen and chest was unremarkable. The patient's history included hypertension, bilateral tubal ligation, and total abdominal hysterectomy for leiomyomas 6 years earlier. Biopsy of the lesion showed adenocarcinoma. Findings on pap smear, chest radiography, and mammography were negative. A complete evaluation of the gastrointestinal tract (especially colon) was negative for any evidence of a primary neoplasm. The patient had modified radical vulvectomy with bilateral inguinal lymph node dissection.

The surgical specimen consisted of a partial vulvectomy, including posterior portions of labium majus, fourchette, and a portion of perineal skin and soft tissue. The specimen measured 5.5 x 5.0 x 1.6 cm. The surface was dark brown with multiple gray-white nodules, ranging in size from 0.1 to 1.4 cm and was focally ulcerated. On cut section, the subcutaneous tissue was pale yellow and fibrotic. Also received were right and left inguinal lymph nodes.

Microscopic examination revealed a well to moderately differentiated adenocarcinoma in the subcutaneous tissue. The neoplastic cells were directly contiguous with the surface epidermis but did not exhibit epidermotropic migration (Fig 1, a). The tumor was composed of glands lined by large columnar epithelial cells with vesicular nuclei and prominent nucleoli. Many cells contained intracytoplasmic mucin, and occasional goblet cells were seen. The neoplastic glands evoked a desmoplastic response within the stroma, which also exhibited a moderate mononuclear inflammatory infiltrate (Fig 1, a and b). The neoplastic cells stained positively for mucicarmine (acid and neutral mucin), alcian blue (acid mucin), and alcian blue PAS (acid and neutral mucin) and exhibited a positive diastase-resistaut PAS reaction. The colloidal iron stain was negative. The immunohistochemical stains indicated a universal positivity of neoplastic cells for carcinoembryonic antigen (Fig 2, a), broad spectrum cytokeratins, and p-53 antige n (Fig 2, a and b). There was also focal positive immunoreactivity for Ras-10 oncoprotein. The tumor was negative for estrogen and progesterone receptors, Bcl-2 oncoprotein, and C-erB2 (Her-2/neu) antigens. At the base of the tumor were several benign glands with resemblance to colonic epithelium (Fig 1, c). These benign glands were immunohistochemically negative for CEA and p-53 antigens (Fig 2, c) and were presumably cloacal remnants. All resection margins and bilateral inginal lymph nodes were negative for neoplastic cells.

The patient was well, with no metastases or other primary neoplasms, 18 months after operation.

DISCUSSION

Primary adenocarcinomas of the vulva are rare. Possible origins of these lesions include Bartholin's glands, sweat glands, ectopic breast tissue, paraurethral glands, sebaceous glands, minor vestibular glands, Gartner's duct remnants, foci of endometriosis, and misplaced cloacal remnants. [1,2] In our case, the possibility of metastatic carcinoma was excluded by the absence of any known primary lesions historically and by a detailed evaluation of the gastrointestinal tract, breast, and lung for evidence of any primary tumor.

The possibility of a primary Bartholin's gland tumor was excluded by the fact that the lesion was located away from the normal Bartholin's gland area of distribution (labium majus) and also the fact that normal Bartholin's glands were not recognized in the vicinity of the tumor. Sweat gland origin was also excluded, since there were no intracytoplasmic iron granules or decapitation secretions and the tumor had a diastase resistant PAS reaction. [7] A paraurethral (Skene's) and minor vestibular gland origin can be excluded by the anatomic location of the neoplasm (ie, perineum). Also, carcinoma derived from these tissues is not known to stain with alcian blue, [1,6] in contrast to the present case. The possibilities of adenocarcinoma arising from ectopic breast tissue, sebaceous glands, and endometrium were excluded by the histopathologic and immunohistochemical features of our patient's lesion.

Embryologically, the labia minora develop from the urethral folds, while the labia majora develop from the labioscrotal folds. Both of these embryologic structures are closely associated with cloacal development. The sigmoid colon and rectum are derived from the hindgut and cloaca. Occasionally, remnants of the cloaca remain within the vulva and retain the ability to undergo neoplastic transformation with differentiation into an adenocarcinoma similar to a primary adenocarcinoma of the colon. [46]

The histopathologic, histochemical, and immunohistochemical features of this case are similar to those of a large intestinal adenocarcinoma and similar to that described by Tiltman and Knutzen [5] and Rhatigan and Mojadidi [8] in their reports of adenocarcinoma arising from cloacal remnants. These patients have generally done well after wide local excision.

References

(1.) Wilkinson EJ: Premalignant and malignant tumors of vulva. Blaustein 's Pathology of the Female Genital Tract. Kurman RJ (ed). New York, Springer-Verlag, 4th Ed, 1994, pp 87-129

(2.) Gompel C, Silverberg SG: Pathology in Gynecology and Obstetrics. Philadelphia, JB Lippincott Co, 4th Ed, 1994, pp 1-29

(3.) Copeland LJ, Sneige N, Gershenson DM, et al: Bartholin gland carcinoma. Obstet Gynecol 1986; 67:794-801

(4.) Stern BD, Kaplan L: Multicentric foci of carcinomas arising in structures of cloacal origin. Am] Obstet Gynecol 1969; 104:255-266

(5.) Tiltman AJ, Knutzen VK Primary adenocarcinoma. of the vulva originating in misplaced cloacal tissue. Obstet Gynecol 1978; 51:30s-33s

(6.) Kennedy JC, Majmudar B: Primary adenocarcinoma of the vulva, possibly cloacogenic. a report of two cases. J Reprod Med 1993; 38:113-116

(7.) Wick MR, Swanson PE: Cutaneous Adenexal Tumors: A Guide to Pat hologic Diagnosis. Chicago, ASCP press, 1991, pp 1-77

(8.) Rhatigan RM, Mojadidi AM: Adenosquamous carcinoma of vulva and vagina. Am J Clin Pathol 1973; 60:208-217

KEY POINTS

* The majority of cases of primary adenocarcinomas of the vulva are reported to arise from Bartholin's glands. Other possible origins include sweat glands, ectopic breast tissue, paraurethral glands, sebaceous glands, minor vestibular glands, Gartner's duct remnants, foci of endometriosis, and misplaced cloacal remnants.

* The histopathologic, histochemical, and immunohistochemical features of the case presented are similar to those of a large intestinal adenocarcinoma.

* These neoplasms usually exhibit an indolent behavior, and patients have reportedly done well after wide local excision.