Angiomyofibroblastoma of the female genital tract: analysis of 17 cases including a lipomatous variant

The clinicopathological and immunohistochemical profile of 17 cases of angiomyofibroblastoma (AMF) arising in the genital tract of females is reported. The lesions usually presented as painless masses and were located in the superficial vulvar region (15 cases), canal of Nuck (one case), and perineum (one case) in women ranging in age from 38 to 60 years (median, 46 years). The tumors were well delineated and ranged in size from 2 to 8 cm in greatest dimension. Microscopically, they were composed of spindled and epithelioid mesenchymal cells arranged in cords and nests preferentially arrayed around numerous small to medium-sized vessels. Mitotic activity ranged from 0 to 7 mitoses per 50 high-power fields (HPF) with no abnormal mitotic figures. Minimal nuclear atypia was appreciated. Intralesional fat was present in 12 cases and in two of these cases constituted most of the tumor (lipomatous variant of AMF). Tumor cells expressed vimentin (five of five cases), estrogen receptor protein (six of six cases), progesterone receptor protein (five of six cases), desmin (six of eight cases), CD34 (one of six cases), and smooth muscle actin (one of seven cases). None of the eight women with follow-up of up to 25 years (mean, 7.8 years) after simple excision developed a recurrence. This study confirms the benign nature of AMF, broadens its morphological spectrum to include a lipomatous variant, and proposes an origin from a perivascular stem cell that is capable of myofibroblastic and fatty differentiation.     

Epithelioid sarcoma: a clinicopathologic review of 55 cases

OBJECTIVE: To identify any clinical and pathologic features of treatment modalities that are predictive of outcome in patients with epithelioid sarcoma, a rare slow-growing soft tissue tumor most commonly occurring in the distal extremities of young adults. DESIGN: We reviewed the institutional files for cases of epithelioid sarcoma for the period 1956 to 1991 and analyzed the effect of various factors on survival. MATERIAL AND METHODS: Fifty-five cases of epithelioid sarcoma were found, and the relevant clinical, pathologic, treatment, follow-up, and outcome features were assessed. RESULTS: All tumors were treated initially by operative resection. The recurrence rate progressively decreased with increasing aggressiveness of the initial operation; however, no difference was noted in metastatic rate. Overall, the recurrence rate was 38% and the metastatic rate was 47%. At the end of a mean follow-up of 102 months, 69% of patients had no evidence of disease, 27% had died of the disease, and 4% were alive with disease. Increasing tumor size, necrosis of more than 30%, and vascular invasion correlated significantly with a worse prognosis. CONCLUSION: Epithelioid sarcoma should be considered a malignant neoplasm with a significant potential for aggressive behavior, and close follow-up of affected patients should be maintained for many years. Initial treatment should be aggressive in an attempt to prevent recurrence.     

Fibromatosis of soft tissue type involving the female genital tract: a report of two cases

The presence of a fatty liver often complicates the interpretation of abdominal computed tomography (CT). Abnormalities in or adjacent to the liver, including dilated bile ducts, liver masses and subphrenic collections, may be masked by the fatty liver. Furthermore, normal structures may simulate pathological conditions. Five cases are presented to illustrate some of these diagnostic pitfalls.     

Actinomycosis of the female genital tract

1 Intracellular recordings were made from smooth muscle cells of the mouse vas deferens. Excitatory junction potentials (e.j.ps) were evoked by stimulation of the intramural nerves. 2 Normorphine (50 nM-5muM) depressed the amplitude of the e.j.p. The ED50 was 430 nM. The latency of the e.j.p. and the resting membrane potential of the smooth muscle cells were unaffected by normorphine. 3 The depression of the e.j.p. by narcotic analgesic drugs was stereospecific. 4 Naloxone (100 nM) completely reversed the depression of the e.j.p. produced by normorphine (1 muM). Naloxone (100 nM) alone did not alter the amplitude of the e.j.p. 5 Normorphine (1 muM) did not prevent the depolarization of the smooth muscle cells produced by exogenous noradrenaline (10 muM). 6 It is concluded that narcotic analgesic drugs act directly upon the transmitter release sites to reduce the amount of noradrenaline liberated by each nerve impulse.     

Immunization of the female genital tract with a DNA-based vaccine

Vaccines are being sought for contraception and the prevention of sexually transmitted diseases. However, progress is slow in this area largely because of lack of information on induction of protective immune responses in genital tract mucosa. In this study, we investigated whether in vivo transfection with a model DNA-based antigen delivered by gene gun technology would induce an antibody response detectable in vaginal secretions. Female rats were immunized with plasmids encoding human growth hormone (HGH) under the control of a cytomegalovirus promoter (pCMV/HGH) via vaginal mucosa (V), Peyer's patch (PP), and/or abdominal skin (S) routes. Localization of HGH in the target tissues demonstrated that all three sites can be transfected in vivo with pCMV/HGH. Vaginal tissues expressed roughly the same level of plasmid as skin. Antibodies to HGH were detectable in serum and vaginal secretions in rats immunized with pCMV/HGH. In the rats primed and boosted vaginally, vaginal immunoglobulin A (IgA) and IgG antibody titers to HGH were sustained for at least 14 weeks, whereas rats immunized via other routes and protocols (S/V, S/S, PP/PP, or PP/V) did not consistently sustain significant vaginal antibody titers beyond week 6. DNA-based immunizations administered by the gene gun may be an effective method of inducing local immunity in the female genital tract.     

Mucosal immunity in the female genital tract

Immunoglobulin (Ig)-producing cells in mucosal tissues represent quantitatively the most important humoral immune system of the body. All exocrine tissue sites contain immunocytes (B-cell blasts and plasma cells) that mainly synthesize dimers and larger polymers of IgA (collectively called pIgA) with incorporated J chain. Such pIgA is actively transported to external secretions as secretory IgA (SIgA) by the polymeric Ig receptor (pIgR), a transmembrane epithelial glycoprotein also called the secretory component (SC). The same transport mechanism includes pentameric IgM to generate SIgM. Although the most active SIgA system occurs in the gut, secretory immunity also operates in the female genital tract, with considerable pIgA production in the cervical mucosa and fallopian tubes. The origin of these local IgA immunocytes remains undefined. In mice, both lymphoid tissue in the large bowel (GALT) and nasopharynx (NALT) have been suggested as inductive sites for B cells homing to the urogenital tract. It is well established that integrin alpha 4 beta 7 is used by primed lymphoid cells to enter the intestinal lamina propria through interactions with mucosal addressin cell adhesion molecule (MAdCAM)-1 expressed on venule endothelium. However, alpha 4 beta 7 does not appear to be an important homing molecule in the airways, and the same might be true for the urogenital tract; this could explain that high levels of IgA antibodies occur in cervicovaginal secretions of mice after nasal immunization. The endometrium can likewise perform pIgR-mediated external translocation of pIgA that in this tissue appears to be mainly derived from serum, partly under hormonal regulation. In addition, paracellular diffusion of serum-derived and locally produced IgG through epithelia is an important part of humoral immunity in the female genital tract.     

Primary osteogenic sarcoma of the breast: a clinicopathologic analysis of 50 cases

Extraskeletal osteosarcomas are rare. Few primary mammary osteosarcomas have been reported; many of these have been described in association with a biphasic tumor. Fifty pure osteosarcomas of the breast, diagnosed between 1957 and 1995, were reviewed after excluding those of biphasic origin. The absence of epithelial differentiation was confirmed using a panel of immunohistochemical markers in 32 cases and using ultrastructural evaluation in an additional four cases. Tumors occurred in 49 women and one man; age ranged from 27 to 89 years (median, 64.5 years). One patient received radiotherapy for ipsilateral breast carcinoma 9 years before presentation. Patients were treated by excisional biopsy (n = 13), tylectomy (n = 5) or mastectomy (n = 32). All axillary nodes, dissected in 20 patients, were free of tumor. One patient had extramammary spread at diagnosis. The neoplasms were 1.4 cm to 13.0 cm (mean, 4.6 cm), and 60% were grossly circumscribed. Tumors were classified as fibroblastic (n = 28), osteoclastic (n = 14), or osteoblastic (n = 8). Of 39 patients with available follow-up information, locally recurrent (n = 11) and metastatic (n = 15) disease developed in 23 (59%) at a mean of 10.5 and 14.5 months from diagnosis. Eight (73%) patients in whom local recurrence developed were treated with excisional biopsy or tylectomy; of these, seven had a positive margin. Sixteen (41%) patients died of disease at a mean of 17.1 months, within 20 months of onset of metastases, most commonly to the lung. Mammary osteosarcomas are aggressive tumors with a propensity for blood-borne rather than lymphatic spread. Total excision without axillary dissection is advised.     

Biopsy of lesions of the female genital tract

Surgical biopsies are often the bedrock of contemporary medical care--the foundation upon which many subsequent and important medical decisions are based. The methods described herein have been found to be very reliable and to produce diagnostic material of high quality. Although some clinics have been reluctant to rely on FNA cytopathologic diagnoses, always insisting on traditional biopsies for histopathologic study, we have relied on both biopsy methods for more than 15 years. The diagnostic accuracy of both methods is greatly improved by attention to technical detail and adherence to an established protocol. Neither method is exclusively applicable in all clinical settings.     

Common congenital anomalies of the female genital tract

The impact of common congenital anomalies of the female genital tract is hugely variable. Some anomalies are asymptomatic chance findings requiring no intervention. Others have a major impact on the potential for sexual activity and fertility. A good knowledge of basic embryology is important to understand the pathogenesis and clinical features of these anomalies. All gynaecologists should be aware of these conditions and possible clinical presentations. Whilst some conditions, such as imperforate hymen require a simple surgical intervention, other more complex anomalies need careful assessment and accurate pre-operative assessment to optimise the long-term outcomes. The contribution of uterine anomalies to subfertility is poorly understood and the role of uterine surgery needs further research.     

Salivary duct carcinoma (clinicopathologic study of 11 cases)

Eleven cases of salivary duct carcinoma were studied clinicopathologically. The clinical features are as follows: men outnumber women; arise most frequently within the parotid glands; rapidly enlarging mass; obvious symptoms of invading nerves; high rates of cervical lymph node and distant metastases; poor patient's prognosis. Its histologic features were shown by the various stages of development of duct carcinoma including dysplasia, carcinoma in situ, papillary, cribriorm, solid and commedo patterns. In addition to the intraductal carcinoma, there is the invasive carcinoma with obvious infiltration into the surrounding tissues. Its treatment requires the combination of radical surgery with postoperative radiotherapy.     

Extraskeletal osteosarcomas: a clinicopathologic study of 25 cases

OBJECTIVE: To describe a clock drawing task (CLOX) designed to elicit executive impairment and discriminate it from non-executive constructional failure. SUBJECTS: 90 elderly subjects were studied (45 elderly and well persons from the independent living apartments of a continuing care retirement community and 45 patients with probable Alzheimer's disease). The clock drawing performance of elderly patients was compared with that of 62 young adult controls. METHODS: Subjects received the CLOX, an executive test (EXIT25), and the mini mental state examination (MMSE). The CLOX is divided into an unprompted task that is sensitive to executive control (CLOX1) and a copied version that is not (CLOX2). Between rater reliability (27 subjects) was high for both subtests. RESULTS: In elderly subjects, CLOX subscores correlated strongly with cognitive severity (CLOX1: r=-0.83 v the EXIT25; CLOX2: r=0.85 v the MMSE). EXIT25 and MMSE scores predicted CLOX1 scores independently of age or education (F(4,82)=50.7, p<0.001; R2=0.71). The EXIT25 accounted for 68% of CLOX1 variance. Only the MMSE significantly contributed to CLOX2 scores (F(4,72)= 57.2, p<0.001; R2=0.74). CLOX subscales discriminated between patients with Alzheimer's disease and elderly controls (83.1% of cases correctly classified; Wilkes' lambda=0.48, p<0.001), and between Alzheimer's disease subgroups with and without constructional impairment (91.9% of cases correctly classified; Wilkes' lambda=0.31, p<0.001). CONCLUSIONS: The CLOX is an internally consistent measure that is easy to administer and displays good inter-rater reliability. It is strongly associated with cognitive test scores. The pattern of CLOX failures may discriminate clinical dementia subgroups.     

Partial moles: a clinicopathologic study of 25 cases

This study is based on a review of all moles diagnosed at the Kaplan Hospital in Israel from 1968 to 1977. Histologic reevaluation revealed that of a total of 72 moles, 47 (65%) were complete and 25 (35%) partial. In contrast to complete moles, about one third of the partial moles showed fetal parts. An analysis of the patient records showed smaller uteri, less vaginal bleeding, absence of severe vomiting, lower gonadotropin levels, and normal follow-up in patients with partial moles as compared with those who had complete moles. These results indicate that the partial mole is a distinct clinicopathologic entity that can be suspected by the clinician and confirmed by the pathologist on morphologic grounds, even in the absence of cytogenetic analysis.     

"HPV effect" in the female lower genital tract. A community study

OBJECTIVE: To determine the distribution of "human papillomavirus (HPV) effect" and intraepithelial neoplasia in the lower female genital tract in one community with a prospective study. STUDY DESIGN: In a family practice setting, colposcopy was offered to all women presenting for a routine cervical cytologic smear. Directed biopsies were taken from areas staining abnormally with acetic acid or iodine. RESULTS: This study of 224 women showed a high incidence of HPV effect in the lower genital tract (68%), including 18% on the vulva. The age distribution suggests a coital influence. A five-year review showed persistence of HPV effect on the vulva or vagina in only one patient. One other woman developed cervical intraepithelial neoplasia (CIN) 1. CONCLUSION: HPV effect is common in the lower genital tract of women under the age of 30 years. Colposcopic study suggested that HPV effect on the vulva and vagina is transient. The relatively high incidence of HPV effect on the vulva may explain why cervical HPV and CIN generally appear only after coitarche, as a consequence of physical transfer. This may help explain why women with a single lifetime sexual partner are not exempt from the risk of cervical cancer or its precursors.     

A study of the anaerobic bacterial flora of the female genital tract in health and disease

Semi-quantitative and qualitative bacterial assessment of the vaginal and cervical flora of a total of 202 women was carried out over a period of six months to determine the bacterial flora in three groups of women and changes caused by prior use of antibiotics. The number was made up of 32 healthy volunteers, 80 women with gynaecological problems and 90 women with gynaecological infections who had had antibiotic treatment prior to this study. Standard methods were used for the investigations. Five main genera of anaerobic bacteria were isolated from all patients. They included, the Bacteroides spp., Prevotella spp., Porphyromonas spp., Peptostreptococcus spp. and Clostridium spp. Five non-sporing gram negative anaerobic bacteria constituted the bulk of the flora including Prevotella bivia, P. disiens, P. melanogenica, P. asaccharolytica and B. fragilis. The predominant flora was P. bivia occurring in 61 pc of cervical swab specimens of the 80 women with proven gynaecological infections who had not used antibiotics and accounting for 27 pc of the total number of Gram-negative anaerobic bacteria isolated. Escherichia coli and Staphylococcus epidermidis were the most frequently encountered aerobic bacteria. The semi-quantitative counts of the different bacterial species in the patient group were significantly higher than in the control group of healthy individuals (p < 0,025). Similarly, prior antibiotic administration significantly reduced the population and quantitative count of the anaerobic bacteria.     

Mantle cell lymphoma: a clinicopathologic study of 80 cases

Mantle cell lymphoma (MCL) is a relatively uncommon yet distinct type of malignant lymphoma whose clinical and pathological characterization has been limited by the small numbers of cases published to date. We studied 80 cases of MCL seen at a single institution over 7 years to determine both clinical and pathological prognostic factors. The patients in this study were predominantly male (70%) and older (mean age, 63 years) and presented with advanced-stage disease (88%). Extranodal involvement was common. Median overall survival (OS) was 43 months. Except for performance status, prognosis was not significantly influenced by clinical prognostic factors. Histologically, MCL architecture was classified as diffuse (78%), nodular (16%), or mantle zone (6%); the OS among these groups was identical. Increased mitotic activity (>20 mitotic figures per 10 high power fields), blastic transformation, and peripheral blood involvement at diagnosis also predicted for a worse outcome, but bone marrow involvement did not. The presence or absence of a translocation t(11; 14) by cytogenetic analysis or a bcl-1 rearrangement by Southern analysis did not significantly predict outcome. In summary, this study of 80 cases of MCL highlights its distinctive clinicopathologic features and shows that increased mitotic activity, blastic morphology, and peripheral blood involvement at diagnosis are prognostically important factors.     

Granulocytic sarcoma of the jejunum: a rare cause of small bowel obstruction

We report the case of a 40-yr-old man presenting with symptoms of small bowel obstruction. Small bowel x-rays revealed a stricture of the mid-jejunum. Push enteroscopy found a polypoid mass at 1 meter of the ligament of Treitz. Histopathological examination of the biopsy and surgical specimens showed a diffuse infiltrate of the mucosa made of medium to large cells, which were stained on immunohistochemistry by the leucocyte marker CD45 and the histiocyte/monocyte marker CD68 but were negative for the B and T cell markers. Cytological examination of the ascitic fluid revealed many myelobasts with cytoplasmic Auer rods and positive myeloperoxidase staining. There was no evidence of blood or bone marrow involvement suggestive of acute leukemia or myeloproliferative disorders. These findings were consistent with the diagnosis of preleukemic granulocytic sarcoma (or chloroma). Chemotherapy led to complete remission, but 21 months later the patient developed an acute myeloid leukemia. He died from aspergillus pneumonitis, 10 months after bone marrow allograft. Preleukemic granulocytic sarcoma of the small bowel is a rare condition and its diagnosis is usually not easy, requiring histochemical or immunohistochemical studies. Most cases have progressed to acute myeloid leukemia.     

Mucoepidermoid carcinoma of the conjunctiva: a clinicopathologic study of five cases

Five patients with mucoepidermoid carcinoma of the conjunctiva were studied. The tumors were located close to the limbus in three patients, in the bulbar conjunctiva in one, and in the lower cul-de-sac in the remaining patient. Histopathologically, they exhibited lobules of tumor cells showing an admixture of epidermoid and mucus-secreting cells. Histochemical stains for mucin were most useful in arriving at a correct diagnosis. Follow-up information revealed that all five tumors recurred rapidly, invading the corneal stroma, intraocular structures, and orbit. Biologically, these tumors appear to be locally aggressive and should be differentiated histopathologically from the conventional squamous cell carcinoma of the conjunctiva, which carries a better prognosis. They should be managed by wide local excision, and the margins should be carefully examined for residual tumor. Frequent follow-up is recommended to detect early recurrence.     

Intravenous leiomyomatosis of the uterus: a clinicopathologic study of 22 cases

Sphingosine-1-phosphate (Sph-1-P) has been implicated as a second messenger in control of cell motility and proliferation (e.g., Sadahira Y, et al., PNAS 89:9686, 1992; Olivera A & Spiegel S, Nature 365:557, 1993). The control mechanism for its synthesis, as catalyzed by sphingosine kinase, is crucial in signal transduction. Synthesis of Sph-1-P in Balb/c 3T3 fibroblasts (A31 variant) is strongly up-regulated by brief treatment of cells with 12-O-tetradecanoylphorbol-13-acetate (TPA). Level of Sph-1-P in PKC-depleted cells is 10-fold higher than in undepleted cells, and a further 5-fold increase occurs after treatment with TPA. In Swiss 3T3 and B16 melanoma cells, Sph-1-P level was unaffected by TPA treatment. Thus, the effect of TPA on Sph-1-P synthesis appears to be cell type-specific.