Biopsy histomorphometry predicts uterine myoinvasion by endometrial carcinoma: a Gynecologic Oncology Group study

A barrier to nonsurgical management of premalignant endometrial disease is the need to perform hysterectomy to exclude concurrent myoinvasive endometrioid adenocarcinoma. Occult adenocarcinoma rates for premalignant disease diagnosed by biopsy or curettage are approximately 40%. We applied the histomorphometric 4-class rule ("4C," which measures epithelial abundance, thickness, and nuclear variation) to diagnostic biopsies to predict myoinvasive cancer outcomes at hysterectomy. Women with endometrial biopsies or curettages having a community diagnosis of atypical endometrial hyperplasia were enrolled in a clinical trial in which subsequent hysterectomy was scored for endometrial adenocarcinoma, and 4C rule ability to predict cancer outcomes was measured. Qualifying biopsies were stratified into high- and low-risk histomorphometric subgroups. Two-hundred thirty-three women had biopsies suited to morphometry and scorable hysterectomy outcomes, of which 46% contained adenocarcinoma. Assignment to a high-risk category by the 4C rule was highly sensitive in predicting any (71%) or deeply (92%) myoinvasive adenocarcinoma at hysterectomy, and assignment to a low-risk group had a high negative predictive value for absence of any (90%) or deeply (99%) myoinvasive disease. Volume percentage epithelium was associated with myoinvasive cancer outcomes above a threshold of 50% (P < .001), and a measure of nuclear pleomorphism was significantly increased (P = .004) in deeply myoinvasive cancers. Formal histomorphometry of endometrial biopsies using the 4C rule has been validated as a means to identify a subset of women with premalignant disease who are unlikely to have concurrent myoinvasive adenocarcinoma and who may qualify for alternative nonsurgical therapies.     

Concomitant well-differentiated adenocarcinoma and leiomyosarcoma of the uterus

We describe a case of a concomitant well-differentiated endometrial endometrioid adenocarcinoma and leiomyosarcoma of the uterus in a 66-year-old woman who presented with a 6-month history of vaginal bleeding. The patient underwent total hysterectomy for endometrial carcinoma diagnosed by endometrial biopsy. Gross examination of the specimen revealed an endometrial mass bulging into the endometrial cavity and an underlying well-circumscribed nodule separated from the endometrial mass by a myometrial band. Frozen section performed at the time of the total hysterectomy rendered a diagnosis of malignant mixed-müllerian tumor. Histologic examination of the permanent sections revealed well-differentiated endometrial endometrioid adenocarcinoma clearly separated from a high-grade leiomyosarcoma. Differential diagnosis included malignant mixed-müllerian tumor. However, no admixture of carcinomatous and sarcomatous elements was present. There were no heterologous elements. To the best of our knowledge, no similar case has been described in the English literature.     

40岁以下妇女子宫内膜癌刮宫活检的病理诊断问题

目的 探讨40岁以下妇女子宫内膜癌刮宫活检的病理诊断。方法对20例40岁以下子宫内膜癌患者的临床病理资料进行回顾性分析。结果子宫内膜样腺癌18例,腺鳞癌(腺癌伴鳞状上皮分化)1例,浆液性乳头状癌并透明细胞癌1例。子宫内膜样腺癌的组织学特点是子宫内膜腺体失去极性,细胞核变大、变圆、核仁突出,染色质粗或呈空泡状,同时子宫内膜间质消失,代之为肉芽组织或纤维组织,常有炎性反应。子宫内膜样腺癌多数仅累及浅肌层,皆无转移。1例子宫内膜腺鳞癌呈双侧卵巢转移;1例浆液性乳头状癌有盆腔淋巴结转移。结论40岁以下妇女的子宫内膜癌多数为高分化子宫内膜样腺癌,应注意与子宫内膜不典型增生及不典型息肉状腺肌瘤鉴别。     

Sporadic microsatellite instability is specific to neoplastic and preneoplastic endometrial tissues

Microsatellite instability is a frequent (13%-24%) finding in sporadic endometrial adenocarcinoma and its precursor lesions, but most studies are limited to patients who already have malignant or premalignant endometrial disease. We performed retrospective testing for microsatellite instability in women in whom cancers showing microsatellite instability developed later and prospective testing in randomly selected normal and anovular endometrial biopsy specimens. Microsatellite instability in cancer-bearing biopsy specimens accurately reflected that seen in matched malignant tissues obtained at hysterectomy. In 1 patient, microsatellite instability developed in a scanty sample of fragmented endometrial tissues 7 years before the onset of endometrial cancer. Prospective testing for microsatellite instability in the endometria of women unselected for subsequent appearance of endometrial cancer showed a very low rate of microsatellite instability. Only 1 endometrial specimen showing microsatellite instability was found among 75 anovulatory endometrial specimens, and none were found in 377 normal endometrial specimens and 46 polyps examined. Microsatellite instability may precede the onset of histologically diagnosed carcinoma but is rare in randomly sampled histologically normal endometrial tissues.     

Microglandular adenocarcinoma of the uterus mimicking microglandular cervical hyperplasia

We present a rare case of microglandular carcinoma of the uterus occurring in 76-year-old woman. The tumor tissue in the curettage specimen showed strong similarity with microglandular hyperplasia of the cervix. Microglandular aggregates of glands with only mild nuclear atypia but without any structures of conventional endometrioid carcinoma were seen. Therefore, a microglandular hyperplasia of the cervix was seriously considered. The following features were helpful in the differential diagnosis: numerous neutrophils and "dirty" amount within glandular lumens; very scarce (but nevertheless present) mitoses; isolated single glands with more endometrioid than endocervical appearance; and strong expression of vimentin, which is unusual for microglandular hyperplasia of the cervix. In the resectate, a conventional well-differentiated endometrioid adenocarcinoma with microinvasion of the myometrium (under 1 mm of depth) was found. Microglandular differentiation has been, however, present in plaque-like proliferation replacing the endometrium and on the surface of conventional adenocarcinoma. Eleven months after the hysterectomy, the patient has no signs of recurrence or metastasis. Our case shows the difficulties in the diagnosis of this lesion and confirms a low aggressiveness that was observed in all 10 cases described to date.     

Clinical relevance of benign endometrial cells in postmenopausal women

Our objective was to determine if the finding of benign endometrial cells on a Papanicolaou (Pap) smear of a postmenopausal woman is associated with endometrial/uterine pathology, independent of symptomatology and hormone replacement therapy (HRT) status. The medical records of 146 postmenopausal patients who had a Pap smear showing normal-appearing endometrial cells between January 9, 1997 and January 12, 2000 were reviewed. Uterine pathology for each patient was determined by reviewing the results of endometrial sampling (endometrial biopsy or dilatation and curettage), hysterectomy, or pelvic sonogram, which were performed within 24 mo of the cytologic smear. The results were then correlated with clinical symptomatology and HRT status of each patient at the time the cytologic smear was obtained. Of the 146 Pap smears coded with "endometrial cells in a postmenopausal woman," 50 were excluded due to prior hysterectomy, perimenopausal status, and absence of further follow-up. Of the remaining 96 women, 27 (28%) had benign pathologic findings including polyps, leiomyomata, and simple hyperplasia without atypia, whereas 11 (12%) had significant pathologic findings including hyperplasia with atypia, adenocarcinoma, mixed Mullerian tumor, and leiomyosarcoma. Of the 11 patients with significant pathology, only one patient did not have abnormal vaginal bleeding but instead had a 30-wk-size irregular uterus on examination, and only 2 patients received hormone replacement therapy. In conclusion, Reporting endometrial cells on Pap smears in postmenopausal women did not lead to the diagnosis of any cases of significant pathology that would have gone unsuspected clinically. Moreover, HRT status did not affect the incidence of normal endometrial cells on Pap smears in postmenopausal women, nor did it aid in distinguishing which postmenopausal women had endometrial/uterine pathology. This calls into question the usefulness of the current Bethesda guideline to report "benign endometrial cells in a postmenopausal woman."     

False-positive squamous cell carcinoma in cervical smears: cytologic-histologic correlation in 19 cases

Cytologic features of squamous intraepithelial lesions (SIL) can mimic those of invasive squamous-cell carcinoma. We compare and correlate the cytological findings of 19 false-positive squamous-cell carcinomas with follow-up cone biopsies or hysterectomy specimens to define which type of dysplasia is more prone to diagnostic errors on cervical Papanicolaou (Pap) smears. Out of 128 patients diagnosed with invasive squamous-cell carcinoma from 1994-2000, 19 (14.8%) with follow-up cone biopsies or hysterectomy specimens were false-positive cases, showing only cervical intraepithelial neoplasia (CIN). We reviewed tissue sections from these 19 cases of CIN for cytologic features of squamous-cell carcinoma, such as markedly pleomorphic and/or dysplastic squamous cells, necrosis, and nucleoli. Twelve of 19 patients (63%) were menopausal. The mean age was 50.5 yr. On review of cervical smears, 18 cases qualified for the cytologic diagnosis of squamous-cell carcinoma, keratinizing type, and one case qualified for squamous-cell carcinoma, nonkeratinizing type. Pleomorphic and/or keratinizing dysplasia was found in 15 out of 19 patients (79%), necrosis within superficial endocervical glands in 9 out of 19 patients (47%), and conspicuous nucleoli in 12 out of 19 patients (63%). One or more of these changes were seen in all but 2 patients (89%). Endocervical gland involvement was present and extensive in 18 of the 19 cases (94%). The mean age was older than expected for SIL (50.5 vs. a reported 40), and matched the mean age found in patients with invasive squamous-cell carcinoma. Pleomorphic and/or keratinizing dysplasia involving endocervical glands may exhibit the cytologic features of squamous-cell carcinoma on cervical Pap smears.     

Performance characteristics of the Indiana University Medical Center endometrial sampler (Tao Brush) in an outpatient office setting, first year's outcomes: recognizing histological patterns in cytology preparations of endometrial brushings

Following successful hysterectomy-controlled trials, Tao brush endometrial cytology with liquid fixation was offered to clinicians for office use. This report recounts our first year's cytology and correlative histology outcomes. One hundred thirteen cases were accrued. Correlative tissue examinations comprising Pipelle (Prodimed, Neuilly-en-Thelle, France) biopsy, hysteroscopy and biopsy, dilatation and curettage, and hysterectomy were available at this institution for 59 cases. In 42 cases, cytology diagnoses could be compared to histology diagnoses. Twenty-five of 63 normal brushings were followed up. Fourteen were normal. Eleven Pipelle biopsies of cytologically atrophic endometrium were quantitatively limited and insufficient for diagnosis. Thirty-seven cases were abnormal, and 15 of these showed nuclear anaplasia. Twenty-eight of the abnormal cases were followed up. All correlative tissue examinations confirmed an abnormality. All 15 cases with nuclear anaplasia showed significant histopathology comprising atypical endometrial hyperplasia, endometrial intraepithelial neoplasia (EIN), endometrial intraepithelial carcinoma (EIC), and invasive adenocarcinoma. There were 13 inadequate endometrial brushings. Three cases had insufficient cellular material. The remaining 10 cases were cellular but were chiefly cervical/endocervical samples. Two of the cellular cases resulted from clinicians failing to replace the protective sheath over the brush bristles before removing the Tao brush from the endometrial cavity. The remaining 11 cases resulted from inaccessibility of the uterine cavity due to a tight or stenotic cervix. The Tao brush is a reliable uterine sampling device that performs well as a diagnostic tool for outpatient assessment of the endometrium of women with patent cervices. An advantage of endometrial cytology is that it accurately represents atrophic endometrium, and it is an effective case-finding tool for EIN and EIC. Women with tight or stenotic cervices are poor candidates for endometrial brushing, and may experience pain if the procedure is attempted. Diagn. Cytopathol. 2000;22:186-195.     

Stromal p16 expression differentiates endometrial polyp from endometrial hyperplasia

Endometrial polyps are very common benign endometrial lesions, but their pathogenesis is poorly understood, except for a few studies indicating the possibility of benign stromal neoplasm. Although the histopathological diagnosis of endometrial polyp on a surgical specimen is straightforward, it is often difficult to differentiate endometrial polyp from endometrial hyperplasia on a biopsy or curettage specimen. Presently, there is no immunohistochemical marker helpful in this differential diagnosis. In this study, we examined p16 expression in 35 endometrial polyps and 33 cases of endometrial hyperplasia that included 16 simple hyperplasias, 14 complex atypical hyperplasias, and 3 complex hyperplasias without atypia. Stromal p16 expression differed significantly between the two groups; it was seen in 31 (89?%) endometrial polyps, but in only 1 (3?%) endometrial hyperplasia. The percentage of p16-positive stromal cells ranged from 10 to 90?% (mean, 47?%) and the positive cells tended to be distributed around glands. Six cases of endometrial hyperplasia within an endometrial polyp were also examined and all cases showed stromal p16 expression. There was no difference in glandular p16 expression between endometrial polyps 33 (94?%) and hyperplasia 27 (82?%). The p16-immunoreactivity was mostly confined to metaplastic epithelial cells in both groups. Stromal p16 expression might be a peculiar characteristic of endometrial polyp and constitute a useful marker for the diagnosis, especially in fragmented specimens from biopsy or curettage. Stromal p16 expression might be a reflection of p16-induced cellular senescence, which has been documented in several benign mesenchymal neoplasms.     

Endometrial brush biopsy (Tao brush). Histologic diagnosis of 200 cases with complementary cytology: an accurate sampling technique for the detection of endometrial abnormalities

We examined 200 cases of endometrial brush biopsy (EBB) using the Tao brush and correlated findings with histologic findings from subsequent dilatation and curettage (D&C) or hysterectomy specimens. Diagnosis by EBB relied mainly on histologic evaluation of H&E-stained tissue sections and was complemented by additional cytologic smear examination. EBB correctly detected the following cases: endometrioid adenocarcinoma, 3; complex hyperplasia with atypia, 1; simple hyperplasia without atypia (SH), 2; and benign endometrium, 177. In 3 cases the diagnosis of atrophic endometrium was made by EBB; corresponding D&C specimens were nondiagnostic. Five cases of SH were interpreted by EBB as proliferative endometrium, and 13 endometrial polyps were not identified by EBB. Nine samples were nondiagnostic. Sensitivity and specificity were 100% for detecting atypical hyperplasia and carcinoma. However, it was difficult for EBB to distinguish SH from disordered proliferative endometrium or to diagnose endometrial polyps. We found that diagnosis by EBB is reproducible; a second pathologist blinded to histologic follow-up correctly identified all adenocarcinoma/atypical hyperplasia cases. EBB is an accurate, safe, and easy procedure that is well tolerated by patients and should be considered in the initial evaluation of high-risk outpatients.     

An investigation of the mechanisms underlying the disparity between rate of residual endocervical adenocarcinoma in situ (AIS) in hysterectomy specimens and clinical failure rate following conservatively treated AIS

The location, amount, and anatomic relationships of adenocarcinoma in situ (AIS) in 5 delayed second cone biopsy excision specimens and 21 definitive-therapy hysterectomy specimens were measured in relation to the neosquamocolumnar junction (nSCJ). All 5 biopsy specimens had 1 to 2 mm of AIS situated at the nSCJ. None had AIS in the proximal endocervix, despite positive or extremely close biopsy margins. Residual AIS in hysterectomy specimens was located proximal to the nSCJ in 19 (90%) of 21 cases. The mean distance between AIS and the nSCJ was 4.9 mm in 12 (86%) of 14 hysterectomy specimens. The mean maximum length of AIS was 4.6 mm in hysterectomy specimens and 1.1 mm in biopsy specimens. Some postbiopsy failures might be de novo neoplasms that begin at the nSCJ rather than recrudescence of persistent AIS. Small amounts of residual AIS following cone biopsy excision might be eradicated by the healing process. These 2 factors might underlie the disparate rates of residual AIS in hysterectomy specimens and postbiopsy excision failures and also explain the poor correlation between biopsy margin status and clinical failure. Factors that impact postbiopsy AIS eradication might be unrelated to de novo AIS beginning at the nSCJ.     

UbcH10 expression in benign, hyperplastic, and malignant endometrial curetted materials: a tissue microarray study

The aim of this study was to investigate the role of UbcH10 expression in the differential diagnosis of benign, hyperplastic, and malignant endometrial tissues and also the relationship of UbcH10 with the clinicopathologic parameters of malignant cases. A tissue microarray was performed for 81 endometrial curettage biopsies, which histological diagnosis had demonstrated to be 13 cases of proliferative endometrium, 7 cases of disordered proliferative endometrium, 5 cases of complex atypical hyperplasia, 24 cases of nonatypical hyperplasia, and 32 cases of endometrioid adenocarcinoma. Expression of UbcH10 was assessed by immunohistochemistry. When groups were compared according to UbcH10 percentages and scores, a statistically significant difference was found only between the carcinoma group and the other groups, except the complex atypical hyperplasia group (P < .05). In the malignant group, UbcH10 percentages and scores were only significantly related to age. There was no significant association between UbcH10 expression and tumor grade and stage. Overexpression of UbcH10 may be a useful indicator of endometrial carcinoma. UbcH10 also deserves further evaluation in the detection of prognostic mean and also for its role in endometrial carcinogenesis.     

My approach to the interpretation of endometrial biopsies and curettings

A major proportion of the workload in many histopathology laboratories is accounted for by endometrial biopsies, either curettage specimens or outpatient biopsy specimens. The increasing use of pipelle and other methods of biopsy not necessitating general anaesthesia has resulted in greater numbers of specimens with scant tissue, resulting in problems in assessing adequacy and in interpreting artefactual changes, some of which appear more common with outpatient biopsies. In this review, the criteria for adequacy and common artefacts in endometrial biopsies, as well as the interpretation of endometrial biopsies in general, are discussed, concentrating on areas that cause problems for pathologists. An adequate clinical history, including knowledge of the age, menstrual history and menopausal status, and information on the use of exogenous hormones and tamoxifen, is necessary for the pathologist to critically evaluate endometrial biopsies. Topics such as endometritis, endometrial polyps, changes that are induced by hormones and tamoxifen within the endometrium, endometrial metaplasias and hyperplasias, atypical polypoid adenomyoma, adenofibroma, adenosarcoma, histological types of endometrial carcinoma and grading of endometrial carcinomas are discussed with regard to endometrial biopsy specimens rather than hysterectomy specimens. The value of ancillary techniques, especially immunohistochemistry, is discussed where appropriate.     

Atypical endocervical glandular cells: Accuracy of cytologic diagnosis

Atypical cells thought to be of endocervical glandular origin often cause diagnostic uncertainty in cervicovaginal smears. For this reason consecutive cases of endocervical glandular atypia diagnosed in smears were correlated with subsequent biopsy diagnoses and then retrospectively reviewed. Smears were originally diagnosed as “mild glandular atypia, probably reactive” or “severe glandular atypia, suggestive of adenocarcinoma in situ” (AIS). Biopsy follow-up was obtained on 34 of 58 patients diagnosed with severe endocervical glandular atypia. Nine patients (26%) had AIS, three with concomitant high-grade squamous intraepithelial lesions (HSIL) and two with invasive adenocarcinoma. Eighteen patients (53%) had HSIL only. Seven had benign changes. Of 152 patients diagnosed with mild glandular atypia, biopsy follow-up was obtained on 40. One patient had AIS; 14 (35%) had HSIL; one had low-grade SIL (LSIL); and 24 (60%) had benign changes. Blinded review of these smears yielded results similar to those in the biopsy follow-up, that is, the prediction of AIS on smears included most cases of AIS, some invasive adenocarcinomas, a significant number of HSIL cases and a few benign lesions. A review diagnosis of “reactive glandular cells” proved to be HSIL in 31% of cases and AIS in one case. We conclude that patients with a diagnosis of severe glandular atypia in smears may prove to have AIS or invasive adenocarcinoma, but often have HSIL without concomitant AIS. In addition, although “reactive” glandular atypia in smears usually reflects a benign condition, a significant minority of such patients prove to have HSIL. © 1995 Wiley-Liss, Inc.     

Schnellschnittdiagnostik bei Erkrankungen des weiblichen Genitaltrakts

Intraoperative frozen sections are particularly important for ovarian tumors because definitive preoperative histology is not possible. The diagnostic accuracy of frozen sections is highest for primary invasive ovarian carcinomas and benign ovarian lesions, followed by borderline tumors and poorest for ovarian metastases and rare neoplasms, such as germ cell tumors. Endometrial carcinoma should be diagnosed preoperatively by curettage or biopsy. For endometrioid endometrial carcinomas the indications for lymphadenectomy are often based on intraoperative assessment of the uterus. The differential diagnosis of low grade stromal neoplasms is based on myometrial invasion and can be supported by assessment of frozen sections as well as the diagnosis of other mesenchymal uterine tumors suspected of being malignant. Frozen sections of pelvic lymph nodes provide the possibility of immediate subsequent para-aortic lymphadenectomy in endometrial and cervical carcinomas but have recently lost importance. Sentinel node biopsy with intraoperative frozen section analysis is routinely performed only for vulval carcinoma. The German Association of Gynecological Oncology (AGO) recommends deferred diagnosis and a two stage surgical procedure for any doubtful intraoperative ovarian histology. Intraoperative frozen sections for endometrial carcinoma and lymphadenectomy specimens as well as for sentinel node biopsies are currently not recommended but are also not completely rejected.     

Clear cell adenocarcinoma present exclusively within endometrial polyp: report of two cases

Endometrial polyp is a common benign lesion that protrudes into the endometrial surface. The incidence of carcinoma within endometrial polyp is thought to be low, however, postmenopausal women with endometrial polyps are at an increased risk. Endometrial clear cell adenocarcinoma is a distinct and relatively rare subtype of endometrial carcinoma, and recent studies have proposed putative precursor lesions of clear cell adenocarcinoma, namely clear cell endometrial glandular dysplasia (EmGD) and clear cell endometrial intraepithelial carcinoma (EIC). Herein, we describe two cases of clear cell adenocarcinoma present exclusively within endometrial polyp and discuss the association of its precursor. Two postmenopausal Japanese females, 66-year-old (Case 1) and 54-year-old (Case 2) presented with abnormal genital bleeding. Cytological examination of both cases revealed adenocarcinoma, thus, hysterectomy was performed. Histopathological studies demonstrated clear cell adenocarcinoma within exclusively endometrial polyp in both cases. The peculiar finding in Case 1 was presence of atypical glandular cells with large round to oval nuclei and clear cytoplasm within the atrophic endometrial glands in the surrounding endometrial tissue, which corresponded to clear cell EIC. A recent study showed that 33% of uteri had at least one focus of clear cell EmGD in endometrial polyps. Accordingly, clear cell adenocarcinoma and clear cell EmGD can occur in association with endometrial polyps more frequently than previously thought. Therefore, detailed histopathological examination is important in diagnosis of endometrial polyps, especially in the postmenopausal women, moreover cytological examination is a useful tool in the postmenopausal women with endometrial polyps.     

Stratified epithelium in prostatic adenocarcinoma: a mimic of high-grade prostatic intraepithelial neoplasia.

Typically glands of prostatic adenocarcinoma have a single cell lining, although stratification can be seen in invasive carcinomas with a cribriform architecture, including ductal carcinoma. The presence and diagnostic significance of stratified cells within non-cribriform carcinomatous prostatic glands has not been well addressed. The histomorphological features and immunohistochemical profile of cases of non-cribriform prostatic adenocarcinoma with stratified malignant glandular epithelium were analyzed. These cases were identified from needle biopsy cases from the consultation files of one of the authors and from a review of 150 consecutive in-house needle biopsy cases of prostatic adenocarcinoma. Immunohistochemistry was performed utilizing antibodies reactive against high molecular weight cytokeratin (34betaE12), p63 and alpha-methylacyl-coenzyme-A racemase (AMACR). A total of 8 cases were identified, including 2 from the 150 consecutive in-house cases (1.3%). In 4 cases, the focus with glands having stratified epithelium was the sole carcinomatous component in the biopsy, while such a component represented 5-30% of the invasive carcinoma seen elsewhere in the remaining cases. The main attribute in all these foci was the presence of glandular profiles lined by several layers of epithelial cells with cytological and architectural features resembling flat or tufted high-grade prostatic intraepithelial neoplasia, but lacking basal cells as confirmed by negative 34betaE12 and/or p63 immunostains in all cases. The AMACR staining profile of the stratified foci was variable, with 4 foci showing positivity, and 3 foci being negative, including two cases that displayed AMACR positivity in adjacent non-stratified prostatic adenocarcinoma. Prostatic adenocarcinoma with stratified malignant glandular epithelium can be identified in prostate needle biopsy samples harboring non-cribriform prostatic adenocarcinoma and resembles glands with high-grade prostatic intraepithelial neoplasia. These 'PIN-like' carcinomas can present in pure form. Recognition of this pattern of prostatic adenocarcinoma is necessary to correctly diagnose such cases as invasive carcinoma.     

Glassy cell carcinoma of the endometrium: a case report and review of the literature

Glassy cell carcinomas are composed of malignant cells showing a "ground glass" cytoplasm, distinct cell membranes, and large nuclei with prominent nucleoli. To our knowledge, only 12 cases of glassy cell endometrial carcinomas (EGCC) have been reported until now. A 63-year-old patient complaining of irregular vaginal bleeding underwent hysteroscopy-guided biopsy revealing a well-differentiated endometrial endometrioid adenocarcinoma. The patient underwent left salpingo-oophorectomy, total abdominal hysterectomy, and pelvic lymphadenectomy. The final diagnosis was FIGO stage IB poorly differentiated endometrial adenosquamous carcinoma with > 90% of glassy tumor cells. The patient is alive, with no evidence of disease for 69 months after diagnosis. We describe an additional case of EGCC and review the data of the literature, emphasizing the need to strictly define the criteria for the diagnosis and the potential usefulness of assessing biologic parameters for the prognostic characterization of this rare entity.     

34betaE12 Cytokeratin Immunodetection in the Differential Diagnosis of Small Cell Tumors of Lung

The group of small cell tumors of the lung includes fine following: (1) small cell carcinoma (SCC) of neuroendocrine (NE) origin, (2) poorly differentiated squamous carcinoma, (3) the rare basaloid (basal cell) carcinomas, and (4) malignant lymphomas, primitive neuroectodermal tumors (PNETs), and rhabdomyosarcomas. The differential diagnosis among these entities carries a heavy therapeutic impact but may be difficult in small biopsy specimens or in cytologic material, especially if necrosis or artifactual alterations are present. The use of additional techniques such as immunostaining for NE markers is not always helpful, since immunoreactive chromogranin A is detectable in only a small percentage of small cell carcinomas. It has recently been reported that in the aerodigestive tract 34betaE12 cytokeratin (CK) immunostaining selectively labels non-NE carcinomas, including squamous cell carcinoma, adenocarcinoma, and the rare basaloid carcinoma. We evaluated the role of such CK immunodetection in the differential diagnosis of small cell lung tumors in cytologic and biopsy specimens. Eighty-one lung tumors diagnosed by means of endoscopic bronchial biopsy, fine needle aspirate, or bronchial washing were collected. They included 43 small cell NE carcinomas and 38 cases used as controls (comprehensive of 2 large cell neuroendocrine carcinomas, 4 carcinoid tumors, 30 cases of non-NE lung carcinomas, 2 cases of bronchial infiltration by non-Hodgkin lymphomas). 34betaE12 CK immunoreactivity was found in 29/30 cases of non-NE carcinomas, but in only 3/43 SCCs. The latter showed positivity in only a few scattered cells. The 2 cases of bronchial infiltration by malignant lymphoma as well as the 4 cases of carcinoid tumors and the 2 cases of large cell neuroendocrine carcinomas were negative. These findings were confirmed in the surgical specimens of operatedon cases. We conclude that, in lung carcinoma biopsies showing a small cell pattern, presence of 34betaE12 CK immunoreactivity favors a non-NE carcinoma, whereas its absence supports the diagnosis of SCC. Int J Surg Pathol 8(4):317-322, 2000