Primary malignant lymphoma of the uterine corpus diagnosed by endometrial cytology. A case report

BACKGROUND: A relatively small number of cases of primary malignant lymphoma of the uterine corpus have been reported, and it is rare for cases to be preoperatively diagnosed by cytology. CASE: A 59-year-old female experienced abnormal uterine bleeding of two months' duration. Preoperative evaluation of endometrial cytology revealed malignant cells. These cells demonstrated a rather round or oval configuration, with a markedly increased nuclear/cytoplasmic ratio, and were isolated and scattered in an inflammatory background. The nuclei were round or oval, and macronucleoli were marked. The cytologic diagnosis was malignant lymphoma. Postoperative histologic evaluation verified the presence of a primary malignant lymphoma in the uterine corpus, with a B-cell phenotype. CONCLUSION: Preoperative endometrial cytology correctly demonstrated malignant lymphoma of the uterine corpus.     

The cytology of vaginal, cervical and endometrial smears obtained at the time of embryo transfer during in vitro fertilization

Seventy-four women enrolled in an in vitro fertilization (IVF) program had cytologic smears of the vagina, cervix and endometrium obtained at the time of embryo transfer (ET). Of these, 68 vaginal, 46 cervical and 25 endometrial smears were available for cytologic examination. Of the 68 vaginal smears, 4% showed a proliferative pattern, 40% were early secretory and 56% were advanced secretory. The 46 cervical smears demonstrated a delayed hormonal effect, with 70% showing a proliferative pattern, 23% early secretory and 7% advanced secretory cytology. Endometrial cells were obtained only when the Jones catheter, which has a side opening, was used. Twenty-two patients had both vaginal smears and suitable endometrial smears. Of these, 8 of the 9 patients with early secretory vaginal cytology had secretory endometrium while 10 of the 12 patients with mid-secretory vaginal cytology had secretory endometrium. The value of endometrial cytology in predicting conception following IVF-ET is unknown. It seems, however, that a good correlation exists between endometrial and vaginal cytology and that the latter may be of value as an additional, noninvasive tool for the evaluation of endometrial development.     

高原鼢鼠发情周期阴道细胞变化特征及血清促性腺激素含量动态

In order to determine the change characteristics of vaginal cells in the estrus cycle and the duration of the estrus cycle, vaginal smears and HE staining methods were used to observe and count the types, morphological changes, and proportions of vaginal cells in plateau zokor (Eospalax baileyi). The hormone secretion dynamics of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the serum of plateau zokor in the estrus cycle were determined by ELISA. The results showed that the main vaginal cells of plateau zokor were leukocytes, nuclear epithelial cells, incompletely cornified epithelial cells, and complete cornified epithelial cells. The proportion of nuclear epithelial cells in the proestrus was significantly higher than that during the other three periods (48. 4 ±3. 09)% (n=12, P < 0. 05). The proportion of complete cornified epithelial cells in the oestrus was the highest and significantly higher than that in the other three periods (59. 73 ±7. 59)% (n=15, P < 0. 05). The proportion of leukocytes in the metestrus and dioestrum was significantly higher than that in the proestrus and oestrus (P < 0. 05). The expression level of LH was the highest in the metestrus (4. 709 5 ±1. 094 0) ng/mL (n=6, P < 0. 05), which showed an increasing trend in proestrus and oestrus, and a decreasing trend in the metestrus and dioestrum. There was no significant difference in the expression level of FSH among the four periods (P > 0. 05); the estrus cycle duration of plateau zokor was 16 to 19 d, the characteristics of vaginal cell types in different stages of the estrus cycle were obvious, and the relative number was statistically significant. The study provided a basis for vaginal smear identification in the estrous cycle and reproductive physiology study of plateau zokor.     

Epidermal growth factor, transforming growth factor-α, and epidermal growth factor receptor expression and localization in the canine endometrium during the estrous cycle and in bitches with pyometra

Gene expression and immunohistochemical localization of epidermal growth factor (EGF), transforming growth factor-α (TGF-α), and epidermal growth factor receptor (EGF-R) were compared between the endometrium of bitches (Canis familiaris) with pyometra accompanied by cystic endometrial hyperplasia (CEH) and that of healthy bitches at similar stages of the estrous cycle. In normal bitches, endometrial TGF-α mRNA levels were highest at proestrus and gradually decreased as the cycle progressed to anestrus. Epidermal growth factor receptor mRNA levels were not significantly affected by the stage of the estrous cycle. Epidermal growth factor mRNA levels were higher at Day 35 of diestrus than at other stages of the estrous cycle (P < 0.05). In bitches with pyometra, endometrial TGF-α and EGF-R mRNA levels did not differ significantly from those at diestrus in normal bitches, but EGF mRNA levels were lower than those at Day 35 of diestrus in normal bitches (P < 0.05). In normal bitches, positive immunohistochemical staining for TGF-α, EGF, and EGF-R was mainly present in the glandular and luminal epithelial cells of the endometrium. In contrast, in bitches with pyometra, immunoreactivity for EGF was clearly present in endometrial stromal cells. Inflammatory cells that had infiltrated the endometrial stroma stained strongly for TGF-α and EGF-R. Luminal and glandular epithelial cells also stained positive for EGF-R. In conclusion, expression of TGF-α by inflammatory cells and a low level of expression and differential localization of EGF may be involved in aberrant growth of endometrial glands and development of CEH.     

Hysterographic appearance and uterine histology at different stages of the reproductive cycle and after progestagen treatment in the domestic cat

The aims of this study were to characterize the hysterographic and histological features of the uteri and to perform immunohistochemistry with proliferating cell nuclear antigen (PCNA) in the cat endometrium at various stages of the reproductive cycle and after treatment with exogenous progestagen. Seventy-four female domestic cats submitted for routine ovariohysterectomy were categorized into six groups: inactive (n=20), follicular (n=9), luteal (n=18), and postpartum (n=12) stages of the reproductive cycle; cats given medroxyprogesterone acetate for estrus prevention (MPA group) (n=12); and cats with uterine pathological lesions (n=3). Hysterography was performed and the relation of the uterine and luminal shape in the hysterogram with the stage of the reproductive cycle as well as with any pathological conditions of the uterus was evaluated. The uteri and ovaries were thereafter surgically removed and sectioned for histological examination. The PCNA was used to demonstrate the expression of endometrial epithelial cell growth. The hysterographic appearance was found to differ between the six groups of cats. A straight uterine cavity was characteristic for cats in the inactive stage, whereas a wavy uterine cavity was characteristic for cats in the follicular stage. In the luteal stage, the luminal cavity of the uteri differed in shape with increasing progesterone concentration from straight to irregular wavy or coiled. The coil shaped uterine lumen seen in the MPA treated and pathological groups was considered also to be an expression of a progestagenic effect. Waviness and coiling of the uterine lumen was related to a proliferation of the endometrial glands, whereas irregular filling defects were indicative of endometrial cystic changes. This study is the first to demonstrate the expression of PCNA in the cat endometrium although no differences were found between the six groups of cats. The hysterographic appearance was found to differ according to stage of the reproductive cycle and pathological conditions. Thus, a normative hysterogram is now available for diagnosing the reproductive stage and uterine changes in cats developing endometrial hyperplasia with and without cystic changes.     

Cervicovaginal cytology in uterine adenocarcinoma and adenosquamous carcinoma. Comparison of cytologic and histologic findings

To investigate the diagnostic accuracy and to characterize the findings in false-negative cases, the results of cervicovaginal cytology in 56 adenocarcinomas and 25 adenosquamous carcinomas (42 cervical, 36 endometrial, 2 metastatic and 1 arising synchronously from both cervix and endometrium) were reviewed, including review of the actual slides in 56 cases. Overall, 80% of the initial cytologic diagnoses resulted in diagnostic curettage (i.e., cytology was effectively positive); 84% of the postreview diagnosis were effectively positive. Nine cytology slides showed no malignant cells; eight of these negative smears showed repair, five were atrophic, two showed a high estrogen effect and one had enlarged atypical bare nuclei. These false-negative diagnoses were associated with an endometrial primary site (P less than .01), endometrioid histology (P less than .005), low-grade or intermediate-grade histology (P less than .005), small size of tumor (P less than .05) and absence of cervical involvement (P less than .005) in those cases in which a hysterectomy was performed. False-negative diagnoses were not associated with an absence of endocervical cells or with scanty cellularity. Of 39 cervical and 28 endometrial carcinomas with a positive cytologic diagnosis (initially or after review of the available slides), cytology correctly identified the primary site in 18% and 54% of the cases, respectively. Cytology incorrectly classified the anatomic site of four cervical and three endometrial carcinomas and considered one case arising in both the endometrium and cervix to be endometrial. Routine cervicovaginal cytology does have a role in screening for uterine glandular carcinoma; to maximize its diagnostic sensitivity, we suggest using a recommendation for curettage in the report of positive cases so that all of the varied cytologic diagnoses associated with glandular carcinomas will receive a uniform clinical response. In those cases with preserved cancer cells, a correlation can be made with the histologic type of the carcinoma, rather than with the anatomic site.     

Preoperative brush and impression cytology in ocular surface squamous neoplasms

OBJECTIVE: Preoperative cytologic diagnoses of ocular surface squamous neoplasms were evaluated and compared with histologic diagnoses. STUDY DESIGN: Impression cytology (Millipore filter paper) and brush cytology were applied to 32 patients who had conjunctival neoplasms. Papanicolaou-stained cytologic preparations and hematoxylin and eosin-stained histologic sections were examined by light microscopy. RESULTS: The brush technique was used on 27 patients; impression cytology was applied in 5 cases. Cytologic and histologic diagnoses were concordant in 26 cases. Squamous cell carcinoma or carcinoma in situ was diagnosed in 18 and dysplasia in 4 cases. Squamous metaplasia and normal-appearing conjunctival epithelial cells were diagnosed cytologically in four cases; of those histologic diagnoses, one was pterygium and three, conjunctival nevus. Four cases revealed discrepancies between the cytologic and histologic preparations. There was one false positive result, and one case was subconjunctival invasion of basal cell carcinoma of the eyelid. CONCLUSION: Impression and brush cytology are fast, cost-effective, reliable and noninvasive diagnostic tools for ocular surface squamous neoplasms. However, the brush technique has several advantages over impression cytology.     

Epithelial cytologic atypia in a fine needle aspirate of an invasive thymoma. A case report.

Fine needle aspiration of a superior-anterior mediastinal mass in a 35-year-old man revealed sheets and clusters of epithelial cells intermingled with a few lymphocytes, characteristic of a thymoma. The presence of atypical cytologic features, such as nuclear pleomorphism, large and vesicular nuclei, prominent nucleoli and frequent mitotic figures, in the epithelial cells caused diagnostic confusion with a thymic carcinoma. However, the subsequent clinical and histologic findings were consistent with an invasive epithelial thymoma. The cytologic features in the present case showed that thymoma with intermediate cytology between that of an ordinary thymoma and thymic carcinoma may be encountered in fine needle aspirates of mediastinal tumors. The cytologic differentiation from a carcinoma may be difficult when the degree of epithelial atypia is high. Histologic confirmation is necessary for a definitive 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.     

Quality assurance of canine vaginal cytology: A preliminary study

Regulatory controls of quality assurance in veterinary laboratories are less common than in human reproduction laboratories and the intra- and inter-technician variation in the assessment of canine vaginal cytology has not been reported. This study was designed to determine whether variation in classification of vaginal epithelial cells and interpretation of vaginal cytology smears existed within and between technicians in a canine reproductive laboratory.Sixteen vaginal cytology smears representing different known stages of the oestrous cycle were examined twice by one experienced technician and three inexperienced technicians in a blinded random order study design. Seven assessments were made; counting and classifying one hundred vaginal epithelial cells into four morphological classifications and assessment of three cellular categories. Technicians also interpreted their results and reported the stage of the cycle they thought each slide represented. In addition, selected samples were sent to four external commercial laboratories for interpretation.For the experienced technician, intra-technician variation was low for the morphological classifications and cellular assessments (r = 0.69-0.95). There was more intra-technician variation between results from Examination One and Examination Two for the inexperienced technicians (r = 0.53-0.92 where correlations were found). When inexperienced technicians' results were compared to results from the experienced technician, the inter-technician variation was low; results were correlated for 17 of the 21 observations (four morphological classifications and three cellular assessments across the three technicians) (r = 0.38-0.87). When technician interpretations of stage of the oestrous cycle were compared to the known stage of the cycle for each smear, the experienced technician correctly interpreted 19 of the 32 smears, whilst the three inexperienced technicians correctly interpreted 14, 16, and 18 of the 32 smears. The interpretation of vaginal smears by external laboratories was varied and sometimes inconclusive; 50% of laboratories incorrectly identified metoestrus smears as proestrus and 25% of the laboratories incorrectly identified an oestrus smear as proestrus.The results of this study are highly important for clinicians undertaking canine reproductive assessments since they demonstrate the potential for variability of results. While the greatest precision was found when vaginal smears were examined by an experienced technician (who, on a daily basis, examines many smears), more variability in both the reporting of different cell types and interpretation of the smears was observed by inexperienced technicians and when samples were sent to external commercial laboratories. These findings suggest that suitable quality control programmes should be implemented for laboratories that are undertaking routine assessments of canine reproductive function.     

Performing Vaginal Lavage,Crystal Violet Staining,and Vaginal Cytological Evaluation for Mouse Estrous Cycle Staging Identification

A rapid means of assessing reproductive status in rodents is useful not only in the study of reproductive dysfunction but is also required for the production of new mouse models of disease and investigations into the hormonal regulation of tissue degeneration (or regeneration) following pathological challenge. The murine reproductive (or estrous) cycle is divided into 4 stages: proestrus, estrus, metestrus, and diestrus. Defined fluctuations in circulating levels of the ovarian steroids 17-β-estradiol and progesterone, the gonadotropins luteinizing and follicle stimulating hormones, and the luteotropic hormone prolactin signal transition through these reproductive stages. Changes in cell typology within the murine vaginal canal reflect these underlying endocrine events. Daily assessment of the relative ratio of nucleated epithelial cells, cornified squamous epithelial cells, and leukocytes present in vaginal smears can be used to identify murine estrous stages. The degree of invasiveness, however, employed in collecting these samples can alter reproductive status and elicit an inflammatory response that can confound cytological assessment of smears. Here, we describe a simple, non-invasive protocol that can be used to determine the stage of the estrous cycle of a female mouse without altering her reproductive cycle. We detail how to differentiate between the four stages of the estrous cycle by collection and analysis of predominant cell typology in vaginal smears and we show how these changes can be interpreted with respect to endocrine status.     

Small cell carcinoma of the esophagus. Cytology and immunohistology in four cases.

Four cases of small cell carcinoma of the esophagus diagnosed by cytology, with subsequent histologic confirmation, were reviewed. The presence of small malignant cells in isolation with minimal cytoplasm was the common characteristic cytologic finding. Cellular molding was observed only focally in two cases, and streaking of nuclear material was not observed in any smear. The tumor cells were argyrophilic and not argentaffinic. Immunohistochemically the neoplastic cells were consistently immunoreactive with low-molecular-weight cytokeratins and epithelial membrane antigen. Esophageal washings as well as endoscopic biopsies yielded diagnostic material in all cases, but the histologic material was remarkable for crush artifacts that hindered the microscopic interpretation.     

Ascitic fluid cytology in a case of metastatic malignant mixed mesodermal tumor of the ovary

The cytologic features of the abdominal fluid from a patient with a malignant mixed mesodermal tumor (MMMT) of the ovary are presented. Both malignant epithelial and stromal elements were cytologically appreciated and confirmed by histologic examination. Other ovarian neoplasms that can present with malignant sarcomatous elements or mixed epithelial and sarcomatous elements are discussed; this case documents the importance of recognizing these features when staging patients with unusual ovarian neoplasms. To our knowledge, this is the first complete report of the ascitic fluid cytology of an MMMT of either ovarian or uterine origin.     

Reconstruction of functional endometrium-like tissue in vitro and in vivo using cell sheet engineering

Uterus is a female specific reproductive organ and plays critical roles in allowing embryo to grow. Therefore, the endometrial disorders lead to female infertility. Hence, the regeneration of endometrium allowing fertilized ovum to implant might be valuable in the field of fertility treatment. Recently, cell sheet engineering using a temperature-responsive culture dish has advanced in regenerative medicine. With this technology, endometrial cells were harvested as a contiguous cell sheet by reducing temperature. Firstly, mouse endometrial cell sheets were re-cultured for 3 days to evaluate the function. Histological analyses revealed that endometrial epithelial cell-specific cytokeratin 18 and female-specific hormone receptors, estrogen receptor β and progesterone receptor, were expressed. Furthermore, endometrial epithelial cells constructed epithelial layer at the apical side. Then, endometrial cell sheets from green-fluorescent-protein rat cells were transplanted onto the buttock muscle of nude rat for evaluating the function in vivo. Histological analyses showed that endometrial cell sheets reconstructed endometrium-like tissue, which was found to form uterus-specific endometrial glands having hormonal receptor to estrogen. In this study, endometrial cell sheets were speculated to contribute to the regeneration of functional endometrium as a new therapy.     

A new trick for an old dog: The application of mifepristone in the treatment of adenomyosis

Adenomyosis is also called internal endometriosis and affects about 20% of reproductive‐aged women. It seriously reduces life quality of patients because current drug therapies face with numerous challenges. Long‐term clinical application of mifepristone exhibits wonderful therapeutic effects with mild side‐effects in many disorders since 1982. Since adenomyosis is a refractory disease, we investigate whether mifepristone can be applied in the treatment of adenomyosis. In this study, we investigated the direct effects of mifepristone on human primary eutopic endometrial epithelial cells and stromal cells in adenomyosis. We found that mifepristone causes cell cycle arrest through inhibiting CDK1 and CDK2 expressions and induces cell apoptosis via the mitochondria‐dependent signalling pathway in endometrial epithelial cells and stromal cells of adenomyosis. Furthermore, mifepristone inhibits the migration of endometrial epithelial cells and stromal cells through decreasing CXCR4 expression and restricts the invasion of endometrial epithelial cells via suppression of epithelial‐mesenchymal transition in adenomyosis. We also found that mifepristone treatment decreases the uterine volume, CA125 concentration and increases the haemoglobin concentration in serum for adenomyosis patients. Therefore, we demonstrate that mifepristone could serve as a novel therapeutic drug in the treatment of adenomyosis, and therefore, the old dog can do a new trick.     

Effect of combined administration of estradiol and progesterone on the mitotic cycle of the epithelial tissues of the reproductive tract of ovariectomized white rats

The duration of stages of the cell cycle in the uterine and vaginal tissues of ovariectomized rats, treated with estradiol and estradiol-progesterone, was estimated using the labeled mitosis method. The joint treatment shortened G2 period in epithelial tissues. In the uterine epithelial tissues of estradiol-progesterone treated rats, the duration of S period was prolonged. In all tissues, progesterone stimulated the entry of cells into a second round of DNA synthesis. The estrogen-gestagen treatment inhibited the movement of vaginal epithelial cells from basal to superficial layers.     

Postpartum endometrial cytology in beef cows

The objectives were to characterize postpartum endometrial cytology and to determine the prevalence of subclinical endometrial inflammation and its impact on reproduction in beef cows. Samples for endometrial cytology (low-volume uterine lavage) were obtained from 135 of 137 Angus cows (2-87 d postpartum) in northern Minnesota, 26 d before breeding started. Agreement between examiners for subjective inflammation scores was very high (kappa = 0.971); the correlation between these scores and PMN counts was high (r = 0.83; P < 0.001), validating subjective categorization. The proportion of PMN and large mononuclear cells (principally macrophages) declined with postpartum interval (P < 0.001), whereas small mononuclear cells were consistently present (and not significantly affected by postpartum interval). Pregnancy rate to fixed-time AI was 29% and overall pregnancy rate was 89%. There was no association between cell type and ultimate pregnancy status or day of conception (P > 0.10). Although inflammation later in the postpartum period apparently impaired subsequent reproduction in dairy cows, in cows >50 d postpartum at sample collection in the present study, no cytological parameter significantly predicted final pregnancy status or day of conception. Previous twinning increased the risk of subclinical endometritis (P = 0.02), but not the probability of becoming pregnant (P = 0.14). In conclusion, we inferred that beef cows had the ability to clear uterine inflammation after resumption of ovarian cyclicity.     

Anatomic basis of endometrial cytology

A comparative cytologic and histologic study on 700 hysterectomy specimens showed that the cytologic evaluation of exfoliated cells from the uterine cavity did not correspond to the findings of the histologic examination of the endometrium in about 33% of sexually mature and 30% of postmenopausal women. The findings of both methods did not always coincide because the epithelial cells in the imprints or smears and the epithelial cells lining the glands in the histologic specimens belonged to structures that anatomically have little in common, one being superficial epithelium of the endometrium and the other being the glandular epithelium in the deep layers of the mucosa. This explains the false-negative results in the cytologic examination of the endometrium, especially in cases of glandular hyperplasia and early carcinoma, in which the foci of proliferation are initially covered by small and inactive surface epithelial cells and are inaccessible to cytologic investigation. False-positive cytologic results may occur in cases of irritated surface epithelium in chronic endometritis; this may also happen in women using an intrauterine device, during estrogen therapy, in regenerating mucosa after desquamation or curettage, in early pregnancy and after spontaneous abortion.     

Importance of using guarded techniques for the preparation of endometrial cytology smears in mares

Material for endometrial cytology can be collected by veterinarians using guarded or unguarded swabs, or digitally with a gloved hand, and is an important diagnostic tool in establishing the endometrial health of mares prior to breeding. The aim of this study was to determine whether the use of unguarded endometrial samples is a reliable indicator of the presence of neutrophils in the uterus. Duplicate endometrial smears were collected from 41 genitally normal, non-pregnant fertile mares by both double-guarded swabs (DGS) and in an unguarded manner by digital scraping (DS) of the endometrium. In 17 of the 41 mares, smears were also collected from the cranial vagina by DS. Cytological samples were collected from a further seven non-pregnant mares at different reproductive stages, and tissues (vestibule, vagina and cervix) from four reproductively normal mares were examined histologically after slaughter to detect the presence of neutrophils. Only 3/41 (7.3%) of the DGS endometrial smears had neutrophils present compared to 36/41 (87.8%) of the DS endometrial smears. The percentage of neutrophils in DGS endometrial smears ranged from 0 to 6% (mean = 0.41%), whereas those in the DS smears ranged from 2 to 90% (mean = 22.02%). Neutrophils were present in all vaginal smears (17/17, range=3-56% (mean = 22.18%)). There was a significant positive correlation (r = 0.84; P < 0.001) between the percentage of neutrophils in the vagina and in the DS endometrial smears. More neutrophils were found in the cervix, vagina and vestibule than in endometrial smears during the cycle (P<0.05). Neutrophils were also observed in tissue collected from the cervix, vagina and vestibule from reproductively normal mares at post-mortem. In conclusion, endometrial smears collected using unguarded techniques are very likely to be contaminated with neutrophils transferred from the vagina potentially leading to incorrect diagnosis of endometritis. When collecting samples for endometrial cytology it is important to use guarded techniques to ensure that only the endometrium is sampled to avoid contamination with cells carried over from other areas of the reproductive tract.