Enteric tumours of the lower female genital tract: a report of three cases

Three enteric-type neoplasms of the lower female genital tract are described; an enteric adenocarcinoma of the cervix, an enteric adenocarcinoma of the vagina and a tubulo-villous adenoma of the vagina. The two adenocarcinomas were characterized by the presence of columnar cells with a prominent brush border and an abundance of goblet cells. The tubulovillous adenoma was identical to similar lesions found in the large intestine. The criteria for diagnosis of an enteric adenocarcinoma of the female genital tract are discussed and it is concluded that the histochemical demonstration of o-acetylated sialomucin is the most specific marker of intestinal differentiation. It is suggested that enteric tumours of the cervix arise from foci of gastrointestinal metaplasia. Enteric tumours of the vagina are more likely to develop from cloacal remnants.     

Revising the WHO classification: female genital tract tumours

The upcoming revision of the World Health Organisation (WHO) classification of tumours of the female genital tract is scheduled for release in the second quarter of 2020. It will feature significant changes compared to earlier editions. In this review, we outline the process of revising this important reference source for those diagnosing tumours or engaged in cancer research and describe the significant changes. The WHO classification of tumours is increasingly evidence-based, with a clear update cycle, improved quality of illustrations and content, led by an editorial board comprised mainly of pathologists, but increasingly incorporating input from other disciplines. The advent of the new website allows the use of whole-slide images and hyperlinks to evidence or external bodies that produce guidance on staging or reporting.     

Papillary mucinous metaplasia: a distinct precursor of mucinous adenocarcinoma of the endometrium

Mucinous adenocarcinoma of the endometrium is heterogeneous, consisting of endometrioid adenocarcinoma composed of >50% mucinous cells, low-grade mucinous adenocarcinoma, microglandular adenocarcinoma, and gastric (gastrointestinal)-type adenocarcinoma. Previous studies have reported that papillary mucinous metaplasia is a possible precancerous lesion of mucinous adenocarcinoma with frequent KRAS mutations. Recently, we encountered a case of pure mucinous adenocarcinoma of the endometrium with concurrent papillary mucinous metaplasia in a 35-year-old woman. She underwent 6-month hormonal therapy for atypical endometrial hyperplasia. A follow-up biopsy led to a diagnosis of mucinous adenocarcinoma; therefore, total hysterectomy was performed. The tumor showed abundant intracytoplasmic mucin and mild-to-moderate cytologic atypia with papillary architecture. KRAS mutation analysis revealed a point mutation from GGT to GTT in codon 12. Although papillary mucinous metaplasia showed an overexpression of p16^INK4, especially in the intragrandular papillary tufts, and a low MKi67 labeling index, overt mucinous adenocarcinoma with a loss of P16^INK4a expression showed a high proliferating index of MKI67. The mass presented with stage ІA disease. During follow-up, the patient was stable and showed no recurrence. Considering the histologic similarity and incidence of KRAS mutations between papillary mucinous metaplasia and mucinous adenocarcinoma, papillary mucinous metaplasia may be a precancerous lesion for a subset of mucinous adenocarcinoma of the endometrium.     

Endocrine cells in the female genital tract

Endocrine cells are normal inhabitants of the para-urethral, Bartholin's and endocervical glands and of mesonephric rests. All these cells were characterized as serotonin-storing cells. In the para-urethral and Bartholin's glands, serotonin-containing cells were most often found in the transitional epithelium of excretory ducts. Endocrine cells participated in some pathological conditions. Abundant argentaffin cells were observed among the terminal ductules in chronic bartholinitis and serotonin-storing cells were identified in a peculiar ectocervical epithelium. Numerous serotonin-storing cells were detected in a well-differentiated adenocarcinoma of cervix occurring in a patient with the Peutz-Jeghers syndrome. Argyrophilic cells were present in cases of endometrial carcinomas; a striking feature was the demonstration of gut peptide hormones in an unusual type of endometrial adenocarcinoma. Finally, serotonin-storing cells were a constituent of Brenner tumours. It is suggested that a similar endocrine pattern may be shared by tissues originating from both Müllerian ducts and the urogenital sinus.     

Mucinous metaplasia of breast carcinoma with macrocystic transformation resembling ovarian mucinous cystadenocarcinoma in a case of synchronous bilateral infiltrating ductal carcinoma

Mammary mucinous cystadenocarcinoma (MCA) is a rare, invasive ductal carcinoma (IDC) of the breast that is virtually identical morphologically to MCA of the ovary, pancreas or appendix. Synchronous bilateral breast tumors, not uncommonly encountered in fibroadenoma and lobular carcinoma, are unusual in IDC. Reported herein is a primary MCA of the right breast coexisting with a bilateral ordinary IDC in a 55-year-old Taiwanese woman who underwent modified radical mastectomy of both breasts with bilateral axillary level I and II lymph node dissection. In the right breast a 2.5 cm unilocular mucus-filled cyst was found. It had complex papillae, some of which were supported by delicate fibrovascular stroma, lined by simple to slightly stratified columnar neoplastic epithelial cells with intracellular mucin and an abundance of intracystic extracellular mucin, coexisting with a low-grade ordinary IDC. In the left breast a high-grade ordinary IDC was discovered. The patient had undergone simple abdominal total hysterectomy for myoma uteri along with bilateral salpingo-oophorectomy 10 years previously. Based on pathological studies and a literature review, it is suggested that mammary MCA arises from mucinous metaplasia and macrocystic transformation of ordinary breast carcinoma. A brief discussion of bilateral breast cancers is also given.     

Surfactant protein D in the female genital tract

Surfactant protein D (SP-D) plays a role in innate immunity against various pathogens and in vivo studies have demonstrated that SP-D also has anti-inflammatory properties. SP-D was originally demonstrated in alveolar type II cells, but recent studies have shown extrapulmonary expression of SP-D indicating a systemic role for the protein. This study describes the presence of SP-D in the female genital tract, the placenta and in amniotic fluid using immunohistochemistry and enzyme-linked immunosorbent assay. SP-D was observed in cells lining surface epithelium and secretory glands in the vagina, cervix, uterus, fallopian tubes and ovaries. In the placenta, SP-D was seen in all villous and extravillous trophoblast subpopulations. Endometrial presence of SP-D in non-pregnant women varied according to stage of the menstrual cycle and was up-regulated towards the secretory phase. It is suggested that endometrial SP-D may prevent intrauterine infection at the time of implantation and during pregnancy.     

A variant of intestinal metaplasia associated with gastric carcinoma: a histochemical study

Gastrectomy specimens including 32 cases of carcinoma and 35 cases of peptic ulcer were examined in detail histologically and histochemically to show the distribution of intestinal metaplasia (IM) and types of mucin secreted. A variant of IM, with extensive involvement of both antrum and body and excessive secretion of sulphomucin, was found to be associated with carcinomas showing appreciable extracellular sulphomucin secretion. The identification of such a variant of IM may help the interpretation of gastric biopsies.     

Isolated vasculitis of the female genital tract: a case series and review of literature

To provide a clinicopathologic review of vasculitis confined to the female genital tract, we describe three cases, and we searched PubMed from 1965 to 2006 with analysis of all relevant articles. We identified 118 additional cases in the literature of whom 108 had isolated necrotizing vasculitis similar to classical polyarteritis nodosa (PAN-type), and 10 presented isolated giant cell arteritis (GCA-type) of the female genital tract. In most cases, arteritis was discovered surprisingly. The mean age of these patients was 48.6 years for the PAN-type and 64.1 for the GCA-type. Vasculitis affected a single organ in 88 (81.5%) cases of which 71 (65.7%) involved the cervix in the PAN-type, whereas it was limited in the myometrium in five (50%) cases in the GCA-type. There was no progression to a systemic vasculitis in 99.1% of the cases. A comparable favorable outcome was reported after surgery in all cases with a mean follow-up of 40.8 months. We conclude that isolated vasculitis of the female genital tract is a distinct condition, with two different patterns but a similar favorable outcome after resection. Its knowledge is needed to avoid aggressive evaluation and therapy.     

The dynamics of rapid sperm transport through the female genital tract: evidence from vaginal sonography of uterine peristalsis and hysterosalpingoscintigraphy

Vaginal ultrasonography of uterine peristalsis during the follicularphase of the menstrual cycle demonstrates an increasing frequencyand intensity of subendometrial and myometrial peristaltic wavesas the follicular phase progresses. During this time the numbersof contraction waves with a fundo-cervical direction decreaseconsiderably in favour of waves of contraction with a cervico-fundaldirection. There is evidence that rapid sperm transport throughthe female genital tract is passive and is provided by theseuterine contractions. Using hysterosalpingoscinti-graphy, rapidsperm transport was studied by placing technetium-labelled albuminmacrospheres of sperm size at the external os of the uterinecervix and following their path through the female genital tractAscension of the macrospheres occurred immediately followingdeposition at the external os of the cervix. As early as 1 minthereafter, the macrospheres had reached the intramural andisthmical part of the tube. Quantitatively, the extent of ascensionincreased with progression of the follicular phase. While onlya few macrospheres entered the uterine cavity and even fewerthe tubes during the early follicular phase, the proportionof macrospheres that entered the uterine cavity increased dramaticallyduring the mid-follicular phase despite continuing limited entryinto the tube. During the late follicular phase there was considerableascension of the macrospheres which was directed preferentiallyinto the tube ipsilateral to the dominant follicle. These dataindicate that rapid transport of the spermatozoa through thefemale genital tract is under the endocrine control of the dominantfollicle, ensuring the preferential accumulation of spermatozoaat the site of fertilization.     

Colonization of the respiratory and genital tracts of female mice with Mycoplasma pneumoniae and protection afforded to the genital tract by prior respiratory colonization

Mycoplasma pneumoniae, strain MY 12763, colonized the throats of 6 BALB/c female mice for at least 18 days after intranasal inoculation. The same strain colonized, in high titre, the vagina of 9 of 10 progesterone-treated BALB/c mice for at least 35 days, but none of 10 oestradiol-treated mice. Mice were less susceptible to genital-tract colonization with the multiple broth-passed FH strain of M. pneumoniae, only 3 of 10 becoming colonized. The 6 mice inoculated intranasally with strain MY 12763 were immune to genital-tract colonization with the same strain, whereas 10 mice without respiratory-tract colonization were susceptible. Protection of the genital tract in this way was at least as effective as that afforded by previous genital-tract colonization. In a further experiment, 26 immunocompetent BALB/c mice colonized previously in the respiratory tract were resistant to vaginal colonization, whereas 20 BALB/c nude mice, similarly colonized in the respiratory tract, were susceptible in the vagina, illustrating the importance of cell-mediated immunity. The possible relevance of the findings to the human situation is discussed.     

Chronic duodenitis with gastric metaplasia: electron microscopic study including comparison with normal

Dudoenal biopsies from 11 patients with non-ulcer dyspepsia were examined by electron microscopy. Chronic duodenitis with gastric metaplasia was seen in samples from four patients, and areas of normal-looking duodenal mucosa were present in nine. The metaplastic cells were similar to those previously described in association with duodenal ulcers. They usually showed marked morphological differences from the normal duodenal absorptive cells. The microvilli were distorted and reduced in number, the glycocalyx was ill-defined, the cytoplasm filled with mucous globules and the intercellular spaces, in some areas, were widened and contained acute and chronic inflammatory cells.     

Pancreatic mucinous lesions: a retrospective analysis with cytohistological correlation

The diagnosis of mucinous pancreatic lesions, which include mucinous noncystic adenocarcinoma, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), and mucinous metaplasia, is critical, given different clinical management and prognosis. This retrospective study is done to assess the cytological features and pitfalls associated with these entities in cytological samples.A search for pancreatic cytology specimens with histological confirmation of the various pancreatic mucinous lesions was done from 1988 to 2005: 9 mucinous adenocarcinoma, 14 IPMN, 11 MCN, and 3 mucinous metaplasia. The majority (35/37) had been endoscopic ultrasound-guided fine-needle aspirations. The cellularity, background extracellular mucin, epithelial architecture, mucinous nature of the epithelium, cell shape, and nuclear features were evaluated on the cytology material. Of the 22 cytological features evaluated, the presence of three-dimensional clusters, micropapillary structures, and nuclear atypia, which includes nuclear crowding, increased N/C ratio, anisonucleosis, nuclear membrane contour irregularity, clumpy chromatin, and prominent nucleoli, was found to be consistently associated with mucinous adenocarcinoma. There were no statistically significant cytological features, which helped in differentiating IPMN, MCN, and mucinous metaplasia. There was a relatively high false-positive rate in the IPMN group (5/14, 36%). Review of the histological specimen showed severe dysplastic epithelial change in these cases. One false-positive case of mucinous metaplasia (1/3, 33%) showed marked intraepithelial acute inflammation.The cytological diagnosis of mucinous pancreatic lesions remains challenging, except for mucinous noncystic adenocarcinoma. The findings were largely nonspecific in the differentiation between IPMN, MCN, mucinous metaplasia, and incidentally sampled gastrointestinal epithelium. False-positive diagnosis of adenocarcinoma occurs not infrequently in the setting of IPMN with severe dysplastic epithelial change and in lesions with associated acute inflammation, and can be a pitfall in the diagnosis of these lesions.     

Intermediate filaments of normal and neoplastic tissues of the female genital tract with emphasis on problems of differential tumor diagnosis

Cytokeratins of normal epithelia and of some neoplasms of the female genital tract were studied by immunofluorescence microscopy of frozen sections and by two-dimensional gel electrophoresis of cytoskeletal proteins from microdissected tissues. All normal epithelia were stained with the monoclonal cytokeratin antibody KG 8.13 whereas certain monoclonal antibodies stained only simple epithelia. As revealed by gel electrophoresis the normal epithelia of the ovarian surface, oviduct, endometrium and endocervix contained cytokeratin polypeptides Nos. 7, 8, 18 and 19. In contrast, stratified exocervical epithelium showed a much more complex pattern (polypeptides No. 1, 2, 4, 5, 6, 11, 13, 14, 15, 16, 17 and 19). A similar pattern was found in the vagina. All epithelial neoplasms studied, regardless of the degree of histologic differentiation, were stained with antibody KG 8.13 as well as with conventionally obtained guinea pig antibodies to bovine muzzle prekeratins. The ovarian, endometrial and endocervical epithelial tumors maintained the pattern of their cells of origin, i.e. they expressed only cytokeratins Nos. 7, 8, 18 and 19. In one type of endocervical adenocarcinoma an additional cytokeratin polypeptide (No. 17) was detected. In contrast, the epithelial tumors of the lower genital tract showed a more complex pattern which also showed some differences with respect to that described for the corresponding normal tissue. Thus, in non-keratinizing squamous cell cervical carcinomas, cytokeratins Nos. 5, 6, 7, 8, 13, 14, 15, 16, 17, 18 and 19 were present, whereas the keratinizing cervical cancers showed polypeptides Nos. 5, 6, 13, 14, 16, 17 and 19.(ABSTRACT TRUNCATED AT 250 WORDS)     

Multiple genital tract tumors and mucinous adenocarcinoma of colon in a woman with Peutz-Jeghers syndrome: a case report and review of literatures

We report a very rare case of Peutz-Jeghers syndrome (PJS) composed of multiple genital tract tumors and mucinous adenocarcinoma. A 46-year-old woman presented to our hospital with lower abdominal pain resulting from PJS involves sex cord tumor with annular tubules (SCTAT), ovarian mucinous tumor, ovarian serous tumor, mucinous adenocarcinoma of colon. The CEA concentration is high before surgery, and decreases after the surgery and subsequent chemoradiotherapy. This case demonstrates a classic clinical presentation of a patient with PJS. PJS patients have increased risk of malignancy and early detection and regular surveillance of the high-risk patients with PJS is crucial. Surgery may be required for obstructive gastrointestinal lesions as well as those exhibiting malignant degeneration.     

Enterovirus RNA shedding in the genital tract of childbearing-aged women living in Central Africa

Enteroviruses (EVs) (Picornaviridae) in the female genital tract may constitute possible sources of antenatal or perinatal infection. The presence of EV genomes in the acellular part of cervicovaginal lavages of 119 non-pregnant childbearing-aged African women was determined using a semiquantitative RT-PCR and hybridization detection assay. EV-specific cervicovaginal IgA and IgG antibodies were also detected by immunocapture ELISA assays. Of 119 CVS samples tested, only 10 (8%) were positive for the detection of EV RNA, demonstrating an genital shedding of EVs in African woman. EV-RNA positivity was not associated with the HIV serostatus or with the presence of semen traces in female genital secretion. The microwell hybridization assay of EV amplified RT-PCR products indicated the presence of low levels of EV genomes, ranging from 50 to 100 RNA copies per ml of genital fluids. EV-specific cervicovaginal IgA or IgG antibodies were detected only in two hemoglobin-positive cervicovaginal secretions samples from women without genital EVs. The lack of EV specific IgA or IgG antibody secretion by the cervicovaginal mucosa supported the hypothesis of genital shedding of EVs without ongoing viral replication in the female genital tract. In conclusion, the findings demonstrated the presence of EV genomes in nearly 10% of childbearing-aged women living in Central Africa, and provided the basis of possible antenatal or perinatal transmission of EV from mother-to-child.     

Importance of specimen type in detecting human papillomavirus DNA from the female genital tract

HPV testing is a valuable tool in cervical cancer screening and efficacy assessment of HPV vaccines. Concordance of specimens from three sites for detection of HPV DNA in the female genital tract was evaluated. At a single visit, the following specimens were collected: an endo‐ecto‐cervical swab (EEC), labial/vulvar/perineal/perianal swab (LVPP) and cervicovaginal lavage (CVL). Specimens were evaluated with HPV6, HPV11, HPV16, and HPV18 type‐ and gene‐specific PCR assays. Of the 898 women evaluated at baseline, 232 were HPV PCR positive in at least one specimen. Of these, for HPV6, HPV11, HPV16, and HPV18, respectively, throughout: (a) 70.4%, 40.0%, 65.3%, and 64.1% tested three‐site positive; (b) 13.6%, 30.0%, 19.7%, and 18.8% tested two‐site positive; and (c) 16.4%, 30.0%, 15.0%, and 17.2% tested single‐site positive. For patients who tested single‐site positive for HPV6, HPV11, HPV16, or HPV18, respectively, the specimen was: LVPP in 92.3%, 33.3%, 68.2%, and 72.7%; EEC in 0.0%, 33.3%, 18.2%, and 9.1%; and CVL in 7.7%, 33.3%, 13.6%, and 18.2%. Combining results of swab specimens together increases detection of HPV6, HPV11, HPV16, and HPV 18, respectively, to 98.7%, 90.0%, 97.9%, and 96.9%. HPV DNA is detectable from all three sites using type‐specific PCR assays; most women who tested positive for a given HPV type were positive for that type in all three specimens. J. Med. Virol. 81:1620–1626, 2009. © 2009 Wiley‐Liss, Inc.