Vulvar Paget's disease. Cytologic and immunohistologic diagnosis of a case

An exfoliative smear from the vagina in a case of vulvar Paget's disease extending into the vagina and urethra was cytologically diagnosed as showing a large cell carcinoma. The malignant cells proved to be Paget cells by comparison of the cytologic specimen with subsequent biopsy specimens and by immunohistochemical studies using antibodies for glandular cytokeratin, epithelial membrane antigen, carcinoembryonic antigen and gross cystic disease fluid protein. These studies demonstrated that the Paget cell is probably of apocrine derivation. Exfoliative cytology and immunohistochemistry of exudative vulvar lesions may be helpful in the identification of Paget cells.     

Cytologic diagnosis of Bartholin's gland adenocarcinoma

An adenocarcinoma of Bartholin's gland was diagnosed by a smear of a swollen lesion of the left vulva, with confirmation on the subsequent surgical specimen. This appears to be the second such case in which the diagnosis was established by cytologic examination of the smear. This rare tumor should be considered in patients presenting with vulvar swellings; cytologic examination can be useful in its early diagnosis, as demonstrated by this case.     

p16 Expression in Squamous Lesions of the Female Genital Tract

The aim of this study was to examine the role of p16 in the pathogenesis of squamous carcinoma of the gynecologic tract. Squamous carcinoma and carcinoma in situ from the female genital tract were examined for the expression of p16 by paraffin immunohistochemistry. About 74% (40/54) of cases showed p16 expression. By primary site, 77% (23/30) of cervical, 67% (6/9) of vaginal and 85% (11/13) of vulvar primaries expressed p16, but two endometrial primary squamous carcinomas were negative (0/2). In addition, p16 was not identified in non-dysplastic tissue and low grade dysplasia. In cases where there were matched vaginal or vulvar and cervical primaries in a given patient, there was concordant positive p16 expression. It is concluded that p16 is frequently expressed in squamous carcinoma of the cervix, vagina and vulva, but not seen in cases of benign and low grade lesions. It may be a marker of transformation from a low to a high grade lesion. More cases of endometrial primaries need to be studied to see if these evolve by a p16-independent pathway.     

Cytologic detection of urothelial cancer and other abnormalities in a cohort of workers exposed to aromatic amines

A total of 541 members of a cohort at increased risk for occupational bladder cancer underwent a 33-month program of screening with urine cytology. Selected workers received further urologic study with cystoscopy and bladder biopsies. Eight workers had positive or suspicious cytologic findings. Only one of the eight had a prior history of bladder cancer. Biopsies showed invasive carcinoma and/or nonpapillary carcinoma in situ in five workers in this group, severe atypia in one, and no significant abnormality in two. Of 56 workers who had atypical cytologic findings, 16 had bladder biopsies, which showed atypia of flat urothelium in 11, nonpapillary carcinoma in situ in one, noninfiltrating papillary carcinoma in one, and no significant abnormality in three. The cytologic detection of urothelial abnormalities often required more than a single specimen. Since the cohort in this study may develop more bladder cancers with the passage of time, continued follow-up is indicated.     

Cytologic diagnosis of vaginal metastasis from renal cell carcinoma. A case report

BACKGROUND: Metastasis of renal cell carcinoma to the vagina is rare, although it may be the first evidence of the existence of the primary tumor. CASE: A metastatic deposit of renal cell carcinoma in the vagina was diagnosed by cytology as clear cell adenocarcinoma, which was confirmed by biopsy. Radiographic and ultrasound examinations confirmed the renal site of origin, which was corroborated by immunohistochemistry of the biopsy specimen. CONCLUSION: When a cytologic diagnosis of vaginal clear cell adenocarcinoma is made, metastasis of renal cell carcinoma should be considered in the differential diagnosis.     

Hydrotubation for diagnosing carcinoma in situ of the fallopian tube. A case report

BACKGROUND: Primary adenocarcinoma of the fallopian tube is rare and not diagnosed until at an advanced stage. We present a case of carcinoma in situ of the fallopian tube in which cytologic examination obtained by hydrotubation facilitated the diagnosis. CASE: A 55-year-old woman presented to Yamaguchi Red Cross Hospital for uterine cancer screening. Endometrial brush cytology revealed adenocarcinoma cells, but endometrial curettage showed no abnormal findings. We performed hydrotubation, collecting abdominal fluid by culdocentesis for cytology. The smear test showed adenocarcinoma with cells similar to those obtained by endometrial brush cytology. Laparotomy showed no abnormalities in the abdominal cavity, and pelvic washing cytology was negative. Based on the positive cytology found by hydrotubation, we performed a hysterectomy and bilateral salpingo-oophorectomy. Postsurgical histology revealed adenocarcinoma in situ of the fallopian tube. CONCLUSION: The present case suggests that cytologic examination obtained by hydrotubation may be useful in diagnosing early tubal cancer.     

Immunohistochemical study of neuroendocrine differentiation in primary glandular lesions and tumors of the urinary bladder

OBJECTIVE: Neuroendocrine (NE) cells are uncommon in primary adenocarcinoma (AC) and other glandular lesions of the bladder, with no recent study series concerning its significance in differential diagnosis, prognosis or biologic significance. STUDY DESIGN: Sixteen primary bladder AC (enteric-type [n = 71, mucinous [n = 6] and not otherwise specified [NOS] [n = 31), 4 cases of urothelial carcinoma with glandular differentiation, 20 cases of glandular cystitis and 3 urachal remnants with intestinal metaplasia constituted the study series. In addition, 20 specimens of normal-looking urothelium, 15 conventional urothelial carcinomas and 5 small cell carcinoma (SCC) cases were included for comparison. NE differentiation included detection of chromogranin A, neuron-specific enolase (NSE) and synaptophysin by immunohistochemistry. The statistical analysis included the chi2 or Fisher exact test. RESULTS: Chromogranin A-positive cells were present in 60% (11 of 16) of primary AC, all of enteric or mucinous type, but not in any of the 3 NOS-type AC investigated. NE differentiation in bladder AC subtypes resulted in highly significant differences between enteric or mucinous vs. NOS type (p = 0.0023). NE differentiation was also different in urachal vs. nonurachal AC (p = 0.020) and primary bladder AC vs. conventional invasive urothelial carcinoma (p < 0.001). Synaptophysin-positive cells were seen in 2 (12.5%) of the 16 primary AC cases, and NSE was negative in the 16 primary bladder AC. All urachal remnants and 70% of glandular cystitis examples had chromogranin A-immunoreactive cells. One of 4 urothelial carcinomas with glandular differentiation had chromogranin A-immunoreactive cells, but this was not significant when compared with primary AC (p = 0.1). Normal-looking bladder urothelium and conventional urothelial carcinoma specimens had no chromogranin A-immunoreactive cells. The 5 SCC cases investigated were positive for chromogranin A. No correlation was found between NE differentiation and outcome of primary bladder AC or urothelial carcinoma with glandular differentiation. CONCLUSION: Primary bladder AC, cystitis glandularis and urachal remnants with intestinal metaplasia showed variable degrees of NE differentiation, with no apparent clinical correlation or prognostic significance. However, the absence of NE differentiation in NOS-type primary bladder AC may help in better defining this uncommon subtype of primary bladder AC.     

Cytologic features of pleural effusion in apocrine sweat gland carcinoma. A case report

BACKGROUND: Carcinoma arising in the apocrine sweat glands is very rare, and there are few reports of the cytologic features. We encountered a case of metastatic apocrine carcinoma in a pleural effusion. CASE: A 46-year-old male had a dark reddish nodule in the right axillary region that was diagnosed as apocrine carcinoma of skin appendage origin. Three years after wide resection and chemotherapy, widespread metastases developed with a massive pleural effusion. Needle aspiration fluid cytology contained clusters of adenocarcinoma. Some tumor cells had abundant cytoplasm or periodic acid-Schiff-positive, coarse granules. Decapitation secretion was occasionally found on the cell surface. Immunohistochemically, the tumor cells were often positive for BRST-2 and BRST-3. CONCLUSION: Cytologic features of metastatic apocrine sweat gland carcinoma show some characteristics of adenocarcinoma. Moreover, its definitive diagnosis in a pleural effusion can be made because of retaining the characteristics of apocrine sweat gland.     

Vulvar syringoma,report of a case and review of the literature

Syringomas are common intraepidermal sweat gland tumors most often found in women around the time of adolescence. Frequent sites of involvement include the lower eyelids and malar areas, however vulvar involvement is relatively rare. These lesions often present as small, multiple, skin-colored-to-yellowish papules and are often associated with increased vulvar discomfort and itching. We present a case of a 29-year old female who presented to her gynecologist complaining of vulvar itching and burning. A small condylomatous-type wart observed on her vulva was biopsied and found to be a syringoma. Because of their clinical presentation and associated symptoms, vulvar syringomas should be considered in the differential diagnosis of any multicentric papular lesion of the vulva, vulvar pain syndrome, and pruritis vulvae.     

A morphometric study of primary adenocarcinoma of the vagina

Primary adenocarcinoma of the vagina accounts for approximately 1% of all invasive carcinomas of the female genital tract. This paper reports on a study of four cases of primary adenocarcinoma (including one with in utero diethylstilbestrol exposure) of the vagina from the files of the Medical University of South Carolina. Both tissue sections and cytologic preparations from each case were evaluated in order to delineate the morphologic characteristics of the cells that compose the lesions. Histologically, the lesions primarily presented the tubular cystic pattern; solid and papillary growth patterns were also seen in one case. The constituent cells included clear cells, hobnail cells and secretory and nonsecretory tubular cystic cells. All specimens were examined for the following parameters: cell population, nuclear area, cytoplasmic area, nuclear/cytoplasmic (N/C) proportions, nuclear and cytoplasmic characteristics. While a fairly detailed profile of the morphologic criteria for hobnail cells was developed, the cellular profiles of the other malignant glandular cells originating in primary vaginal adenocarcinoma remain less certain.     

Advanced primary clear cell carcinoma of the vagina not associated with diethylstilbestrol

BACKGROUND: Primary vaginal clear cell carcinoma occurs in young women exposed to diethylstilbestrol (DES) in utero. Primary vaginal clear cell carcinoma not associated with DES is very rare. We report the clinicopathologic and cytopathologic features of a patient with advanced, sporadic primary vaginal clear cell carcinoma with metastases to liver, lung and paraaortic lymph nodes. CASE: A postmenopausal, 63-year-old woman presented to our department with genital bleeding. A hemorrhagic tumor found in the vagina was diagnosed as a clear cell carcinoma by cytopathologic examination of the tumor smear and by histopathologic examination of a biopsy specimen. A chest radiograph revealed multiple lung metastases, and metastases to the liver and paraaortic lymph nodes were noted on computed tomography and magnetic resonance imaging. The tumor was diagnosed as primary clear cell carcinoma of the vagina, stage IVb (FIGO) based on a normal cytopathologic examination of the cervix, endometrium and ascites; normal appearance of the uterus, ovaries and kidneys on magnetic resonance imaging; and absence of detectable tumor in the urinary tract. The patient died of respiratory failure 31 days after hospitalization. The tumor demonstrated overexpression of p53 protein and did not show microsatellite instability. CONCLUSION: This patient was the second reported Japanese woman with advanced primary vaginal clear cell carcinoma not associated with DES.     

Effect of vaginal distension on blood flow and hypoxia of urogenital organs of the female rat.

Vaginal delivery of children causes traumatic injury to tissues of the pelvic floor and is correlated with stress urinary incontinence; however, the exact mechanism of organ and tissue injury leading to incontinence development is unknown. The purpose of this project was to test the hypothesis that vaginal distension results in decreased blood flow to, and hypoxia of, the urogenital organs responsible for continence, which would suggest an ischemic and/or reperfusion mechanism of injury. Thirteen female rats underwent vaginal distension for 1 h. Thirteen age-matched rats were sham-distended controls. Blood flow to the bladder, urethra, and vagina were determined using a microsphere technique. Hypoxia of these organs was determined by immunohistochemistry. Blood flow to all three organs was significantly decreased just before release of vaginal distension. Bladder blood flow decreased further immediately after release of vaginal distension and continued to be significantly decreased 15 min after the release. Blood flow to both the urethra and vagina tripled immediately after release, inducing a rapid return to normal values. Vaginal distension resulted in extensive smooth muscle hypoxia of the bladder, as well as extensive hypoxia of the vaginal epithelium and urethral hypoxia. Bladders from sham-distended rats demonstrated urothelial hypoxia as well as focal hypoxic areas of the detrusor muscle. We have clearly demonstrated that vaginal distension results in decreased blood flow to, and hypoxia of, the bladder, urethra, and vagina, supportive of hypoxic injury as a possible mechanism of injury leading to stress urinary incontinence.     

Usefulness of silver intensification of immunostaining for cytologic diagnosis of primary melanoma of the female genital organs

OBJECTIVE: To improve the procedure for diagnosing vaginal melanoma with cytopathologic analysis of HMB-45. STUDY DESIGN: The study examined silver intensification of immunostaining of HMB-45 in nine cases of primary melanoma of the vagina and vulva using archival Papanicolaou-stained smears. RESULTS: All nine samples showed positive staining for HMB-45. Five cases showed intensive staining, two moderate and two weak. The positive staining was black in the cytoplasm of melanoma cells but was detected in neither the background nor normal squamous cells. Though destaining of Papanicolaou stain was not performed before immunostaining, the positivity of immunostaining was easily judged. CONCLUSION: After morphologic observation, immunocytochemical study of HMB-45 is possible even though time has passed since the cytologic specimen was obtained. When there is a suspicion of amelanotic melanoma or scantily pigmented melanoma of the vagina and vulva, cytogenesis with HMB-45 is helpful, especially because it involves little invasion.     

Carcinoma In Situ of the Uterine Cervix—A Review of Some Present Clinical Problems

The vaginal smear reveals a spectrum of borderline lesions of the uterine cervix. This spectrum is the source of new clinical problems involving both the recognition and treatment of these various entities. A review of the literature of the past decade indicates that vaginal smears should be obtained regularly every year or two in all women beginning at the onset of sexual activity, but the initial smear may be falsely negative in 10 to 30 percent of cases. When patients have abnormal smears, the precise diagnosis can be established more accurately by cold-knife conization than by multiple punch biopsy.While hysterectomy has been considered “definitive treatment,” late recurrence in the vagina occurs in 1.24 percent of patients so treated. A compilation of 1,100 patients with carcinoma in situ of the cervix treated by conization and follow-up smear reveals that in over 90 percent the disease was controlled by the cone alone, and the remainder by repeat cone or hysterectomy.Precise definition is required in treatment decisions concerning micro-invasive lesions, but these may be well treated by non-radical measures. In almost 500 patients so treated, no death occurred from therapy or tumor metastasis.When carcinoma in situ is found during pregnancy, a coexisting invasive carcinoma must be excluded by appropriate conization or punch biopsy and definitive therapy completed after vaginal delivery.     

Carcinoma in situ of the urinary bladder. Clinical presentation, cytologic pattern and stromal changes

The clinical presentation, cytologic pattern and stromal changes in the cystectomy specimen were studied in a group of 26 patients with carcinoma in situ of the urinary bladder who underwent cystectomy. Only cases in which the nuclear area of the carcinoma in situ cells was over 80 sq micron (large-cell type) were included in this study. The results indicate that the cells from large-cell carcinoma in situ of the bladder exfoliate easily, resulting in a cytologic pattern of predominantly single, highly abnormal cancer cells. Due to the increased exfoliation of the affected epithelium, the bladder stroma is focally denuded; therefore, while cytology may be strongly positive for malignancy in these cases, the histologic diagnosis can be falsely negative when only denuded stroma is biopsied. The edematous stroma causes complaints of "cystitis." The neoplastic urothelium may involve contiguously related epithelial surfaces. When the lesion extends into the prostatic ducts, the patient can have "pseudoprostatitis" complaints. Urethral extension may give penile voiding pain. In one female patient, involvement of the vagina and vulva was found. Carcinoma in situ may develop in patients with papillary low-grade bladder carcinoma during follow-up, with a concomitant shift in the cytologic and clinical patterns; this deserves the consideration and attention of the cytologist and the clinician due to its serious clinical implications.     

Fine needle aspiration cytology of breast cylindroma in a woman with familial cylindromatosis: a case report

BACKGROUND: That sweat gland type tumors occur occasionally in the breast is not surprising, as the breast and cutaneous sweat glands are embryologically related. Cylindromas present most commonly as solitary and sporadic dermal nodules on the face and scalp. Cases of multiple cylindromas are dominantly inherited, and the neoplasms are referred to as "turban tumors" when multiple lesions cover the scalp. Primary cylindroma of the breast has been reported once in the past. To the best of our knowledge, the fine needle aspiration cytology of primary breast cylindroma and its occurrence in the setting of familial cylindromatosis have not previously been reported. CASE: A 59-year-old woman presented with an ill-defined left breast mass. She had a personal and family history of dermal cylindromas on the head and face. Fine needle aspiration cytology demonstrated small, uniform cells with oval nuclei and finely granular cytoplasm, with some cells arranged around conspicuous cylinders of dense, acellular material. Excisional biopsy was recommended to exclude adenoid cystic carcinoma. Tissue biopsy revealed a benign cylindroma arising in breast parenchyma. CONCLUSION: Fine needle aspiration cytology of cylindroma very closely mimics that of adenoid cystic carcinoma. Although extremely rare, primary breast cylindroma is another entity to be included in the cytologic differential diagnosis of bland, basaloid cells associated with globular, extracellular material, a finding most commonly associated with adenoid cystic carcinoma.     

Adenoid cystic carcinoma of the uterine cervix. Cytologic features

A case of primary cervical adenoid cystic carcinoma in a 75-year-old woman is reported. Two cervical smears taken at the time of initial presentation for vaginal spotting were negative; a third smear, taken a year later prior to laparotomy, was diagnosed as positive. The cytologic findings in the positive cervical smear are described and illustrated. The differential diagnosis of the cytologic findings is discussed, and the literature on this lesion is briefly reviewed. The results in this case and others suggest that the diagnosis of cervical adenoid cystic carcinoma in an asymptomatic patient may be missed by routine smear examination.     

Extrauterine malignancies. Role of Pap smears in diagnosis and management.

OBJECTIVE: To further elucidate the cytologic manifestations of extrauterine malignancies, to evaluate their possible distinction from primary cervical malignancies and to analyze their clinical significance and role in staging. STUDY DESIGN: Papanicolaou (Pap) smears in 33 cases with abnormal cells originating in histologically proven extrauterine carcinomas were evaluated. These cases came from the files of the Medical College of Pennsylvania and Lankenau Hospitals. RESULTS: Ovary, gastrointestinal tract and breast were the three most frequent primary sites, accounting for 28 of the 33 cases (85%). The histologic types encountered were adenocarcinoma, 29 cases (88%); mucoepidermoid carcinoma, 1 (3%); small cell carcinoma, 1 (3%); cloacogenic carcinoma and large cell lymphoma, 1 (3%). The following diagnoses were rendered at the time of initial evaluation: adenocarcinoma consistent with metastasis, 21 cases; carcinoma, primary versus metastatic, 2; adenocarcinoma, suspicious for endometrial primary, 2; suspicious for carcinoma, 1; and atypical glandular cells, 7. CONCLUSION: The yield for positive Pap smear diagnoses in extrauterine malignancies is best in patients with an established diagnosis of a primary neoplasm. The degree of tumor differentiation and extent of tumor involvement did not appear to correlate with diagnostic yield. There appeared to be no statistically significant association of tumor diathesis with primary versus metastatic carcinoma and presence or absence of documented local involvement of the endometrium, cervix or vagina. Therefore, while Pap smears can serve as a diagnostic tool in the evaluation of extrauterine malignancies, they are best utilized as an adjunct to tumor staging and patient management.     

Micropapillary variant of transitional cell carcinoma of the urinary bladder: a report of three cases with cytologic diagnosis in urine specimens

BACKGROUND: Micropapillary transitional cell carcinoma is a recently described, aggressive variant of bladder cancer. Its cytologic features in urine have not been previously characterized. CASES: Three cases illustrate the urinary cytologic features of this high grade urothelial carcinoma and its concurrent biopsy findings. This tumor is similar to low. grade urothelial lesions of the bladder, tends to present as micropapillary clusters in urine and yet has high grade nuclear features within these clusters that help with the differential diagnosis of a flat, high grade urothelial carcinoma. CONCLUSION: The micropapillary type of transitional cell carcinoma is a distinct morphologic entity with an aggressive clinical course. Recognizing its presence in urinary cytology, albeit a rare occurrence, is important in distinguishing this lesion from the more indolent, low grade papillary lesions and high grade urothelial carcinomas, which continuously shed single malignant urothelial cells.