Fine needle aspiration biopsy for preoperative workup of pancreatic cystic neoplasms: report of 4 cases

BACKGROUND: Cystic neoplasms of the pancreas comprise a pathologically heterogeneous group of lesions that usually present with similar, nonspecific clinical features. Based on the diagnosis, treatment varies from watchful observation of the lesion to total surgical resection of the pancreas. Therefore the importance of a precise and accurate diagnosis on fine needle aspiration (FNA) biopsy cannot be overemphasized from the patient management standpoint. There is debate regarding the accuracy of FNA diagnosis of cystic lesions of the pancreas. We report 4 cases and review the literature to explore and highlight the cytologic findings and diagnostic pitfalls that may help the cytopathologist accurately distinguish mucinous cystic neoplasm (MCN), intraductal papillary mucinous neoplasm (IPMN), serous cystadenoma (SCA) and ductal adenocarcinoma (DAC). CASES: We present 4 cases of patients with abdominal masses who underwent either computed tomography (CT)-guided or endoscopic ultrasound (EUS)-guided FNA biopsy as preoperative workup. Based on the cytologic diagnosis, the patients underwent surgery. CONCLUSION: Our cases illustrate the cytologic criteria that help the cytopathologist distinguish among MCN, IPMN, SCA and DAC. Correlation with clinical and radiologic findings is strongly advocated for accurate diagnosis. We describe the diagnostic pitfalls frequently encountered in these cases and how to avoid them.     

Rare coexistence of keratinizing squamous metaplasia with xanthogranulomatous pyelonephritis. Report of a case with the role of immunocytochemistry in the differential diagnosis

BACKGROUND: Xanthogranulomatous pyelonephritis (XPN), a rare form ofchronicpyelonephritis, is commonly associated with lithiasis and rarely leads to keratinizing squamous metaplasia. Its manifestations closely mimic those of a renal neoplasm, leading to misdiagnosis of malignancy, often resulting in radical nephrectomy. The role of immunocytochemistry in the preoperative cytologic diagnosis is assessed in the present case report. CASE: A 20-year-old male presented with fever and an enlarging mass in the right renal angle. Ultrasonography revealed a heterogeneous mass in the renal pelvis. Fine needle aspiration cytology was advised to rule out malignancy. Aspiration smears from the mass showed many dissociated cells and clusters of them with abundant vacuolated cytoplasm, vesicular nuclei and prominent nucleoli in some cells. Many desquamated metaplastic squamous cells were also seen. The background was predominantly necrotic, with inflammatory cells. The cytologic possibility of XPN with squamous metaplasia vs. renal cell carcinoma was considered. Immunocytochemical markers, epithelial membrane antigen (EMA) and CD68 (histiocytic marker) were used to determine the nature of the suspicious vacuolated cells; these cells were immunoreactive for CD68 and negative for EMA, thus confirming the cytologic diagnosis of XPN with keratinizing squamous metaplasia. CONCLUSION: The case highlights the presence of metaplastic squamous cells in XPN in smears for the first time. Immunocytochemistry is an essential tool in the preoperative cytologic diagnosis of XPN. The patient can be managed conservatively with antibiotics.     

Fine needle aspiration cytology in a case of diffuse sclerosing carcinoma of the thyroid

The fine needle aspiration (FNA) cytologic findings in a rare case of bilateral diffuse sclerosing carcinoma of the thyroid are described. Along with a generally papillary architecture, the FNA biopsy smears showed a number of features not usually seen in thyroid carcinomas: psammoma bodies, an abundance of squamous metaplasia and a dense inflammatory component. The FNA diagnosis was multifocal papillary carcinoma with squamous metaplasia; histopathologic examination made the final diagnosis.     

Amniotic membrane inhibits squamous metaplasia of human conjunctival epithelium

Squamous metaplasia is a common pathological process that occurs in the ocular surface epithelium. At present, there is no effective treatment for this abnormality. In the current study, we established an ex vivo conjunctival squamous metaplasia model by culturing human conjunctival tissues at an air-liquid interface for durations of up to 12 days. We then investigated the effects of amniotic membrane (AM) on squamous metaplasia through coculture of conjunctival tissues with AM or AM extract. We found that metaplasia features such as hyperproliferation and abnormal epidermal differentiation of conjunctival epithelium could be inhibited by AM or its extract. In addition, existing squamous metaplasia of conjunctival epithelium could be reversed to a nearly normal phenotype by AM. The mechanism by which AM prevents squamous metaplasia may involve downregulation of p38 mitogen-activated protein kinase and Wnt signaling pathways, which were activated in conjunctival explants cultured with an airlift technique. In conclusion, AM can inhibit and reverse squamous metaplasia of conjunctival epithelium. This finding may shed new light on prevention and treatment of diseases that involve epithelial squamous metaplasia.     

Primary squamous cell carcinoma of the pancreas: a case report and review of the literature

ABSTRACT: INTRODUCTION: Primary squamous cell carcinoma of the pancreas is a rare tumor with poor prognosis and is found in the literature only as case reports. The optimal management course remains poorly defined. We present a case of primary basaloid squamous cell carcinoma of the pancreas metastatic to the liver, which was treated with surgery and systemic chemotherapy. Our patient survived for 15 months: the longest survival reported in the literature to date. CASE PRESENTATION: A 70-year-old Caucasian man presented to hospital with a three-month history of weight loss, pruritus and icterus. Imaging studies confirmed the presence of an operable mass lesion in the head of the pancreas. Following a pancreaticoduodenectomy, histology results led us to make a diagnosis of squamous cell carcinoma. Postoperative restaging showed multiple metastases in the liver. He underwent palliative systemic chemotherapy with cisplatin and 5-fluorouracil achieving partial response and an excellent quality of life. He then went on to start second-line chemotherapy, but unfortunately died of sepsis soon thereafter. CONCLUSIONS: This case report emphasizes that achievement of a worthwhile objective and symptomatic palliative response is possible using platinum-based chemotherapy in squamous cell carcinoma of the pancreas.     

Immunologic determination of an epidermal G2-chalone-like factor as a marker of squamous cell structures in the urinary bladder and urine in rats

The epidermal G2 chalone-like substance of the rat skin may be determined by immunochemical methods only in squamous epithelia and it is revealed neither in mucosa of the urinary bladder, nor in urine of control rats. The antigenic activity of the chalone was revealed in 37 extracts of 56 tumors of the rat bladder. All antigen-containing tumors were found to be squamous cell carcinomas, transitional cell carcinomas with squamous cell metaplasia or possessed ultramicroscopic signs of squamous cell metaplasia appearing as "pure" transitional cell carcinomas under light microscope. The epidermal G2 chalone-like substance was present in urine of 7 out of 10 rats bearing the antigen-positive tumors of the urinary bladder.     

Cytologic findings in noninvasive intraductal papillary-mucinous carcinoma of the pancreas. A report of two cases

BACKGROUND: Intraductal papillary-mucinous carcinoma of the pancreas is a new diagnostic term proposed by the 1996 World Health Organization classification of the exocrine pancreas. So far, there have been only a few reports concerning its cytologic findings, especially in noninvasive cases. CASES: The clinical and cytohistologic findings in two cases of noninvasive intraductal papillary-mucinous carcinoma of the pancreas were reviewed. Cytologic specimens were obtained from pure pancreatic juice in the dilated main pancreatic duct during the operation (case 1) and during endoscopic retrograde pancreatography (ERP) (case 2). Both cases showed three-dimensionally or individually scattered tumor cells with an increased nuclear/cytoplasmic ratio and prominent nucleoli. CONCLUSION: Our cases suggest that pancreatic juice cytology during ERP or surgery is useful in diagnosing pancreatic cancers and that it may detect noninvasive intraductal papillary-mucinous carcinoma of the pancreas.     

A series of patients with minimal change nephropathy treated with rituximab during adolescence and adulthood

Background

The treatment of immune suppression dependent minimal change nephropathy (MCN) can be challenging and frequently leads to serious complications. In paediatric patients, successful treatment with rituximab is described in steroid-dependent MCN. There is limited information about the potential efficacy of rituximab for the treatment of MCN in adults and adolescence. We describe our experience with rituximab in adolescent and adult patients with immune suppression dependent MCN.

Results

Ten adolescents and adults with immune suppression dependent MCN and therapy related complications were treated with rituximab. At a mean age of 26 years, about 10.5 years after first presentation, they received two doses of rituximab (375 mg/m²). Maintenance immunosuppressive medication was stopped. After a mean follow-up of 43 months, three patients had four relapses. Three relapses were successfully retreated with rituximab again, after induction therapy with 60 mg prednisone per day. Rituximab was well tolerated and no infectious complications were recorded.

Conclusion

Treatment with rituximab induces a long-term remission of immune suppression dependent MCN in adolescents and adults. A timely treatment with rituximab could be considered to limit side effects of immunosuppressive medication.

     

Staurosporine-induced versus spontaneous squamous metaplasia in pre- and postmenopausal breast tissue

Breast cancers from pre- vs. postmenopausal women display unique characteristics that may be related to differences in epithelial differentiation between these two populations. In addition to lobular development, lactational changes, and involution, breast epithelium can undergo metaplastic alterations, often in association with carcinoma. Because protein kinase C (PKC) regulates differentiation and proliferation in many cell types, we asked whether modulation of PKC activity could define biochemical differences in breast epithelium from pre- vs. postmenopausal women. Organ cultures of normal human breast were treated with PKC agonists and antagonists. Epithelial differentiation was evaluated based on morphologic criteria and the expression of cell-type specific proteins. Staurosporine, a nonspecific but extremely potent inhibitor of PKC, induced squamous metaplasia in eight of eight cases within 2 weeks of treatment. Other inhibitors of PKC, such as calphostin C and tamoxifen, had no effect on epithelial differentiation. Long-term treatment with phorbol esters also did not induce squamous metaplasia. However, stimulation of cAMP levels by forskolin and isobutyl-methyl-xanthene (IMX) rapidly induced squamous metaplasia, as has been previously reported. Surprisingly, squamous metaplasia occurred in 10 of 12 cultures derived from postmenopausal women in the absence of exogenous agents. Untreated cultures derived from premenopausal women never developed this type of epithelium (0 of 11). Therefore, breast epithelium from pre- and postmenopausal women responded differently to in vitro culture. Forskolin/IMX or staurosporine can reproduce these conditions, acting independent of menopausal status. Because staurosporine's action was unique among PKC inhibitors, staurosporine may induce squamous metaplasia of breast epithelium by a PKC-independent mechanism. J. Cell. Physiol. 176:245–254, 1998. © 1998 Wiley-Liss, Inc.     

Benign cellular changes in Pap smears. Causes and significance

OBJECTIVE: We reviewed consecutive cases classified as benign cellular changes (BCC) over a four-month period. STUDY DESIGN: Cases classified as BCC were retrieved from the cytology files. A search was carried out to identify the previous Pap smears and concomitant cervical biopsies. RESULTS: One thousand one hundred three cases (23% of our gynecologic smears) were classified as BCC. Ninety-two patients (8.3%) underwent concurrent cervical biopsies. Specific infections accounted for 8% of BCC cases; reactive changes accounted for 92%. Of the biopsy specimens, 8.3% had no significant pathologic change. The most common biopsy diagnoses were cervicitis (31.5%), immature squamous metaplasia (16.3%) and reserve cell hyperplasia (10.8%). Miscellaneous benign diagnoses accounted for 21.7%. Cervical intraepithelial neoplasia (CIN) 1/human papillomavirus (HPV) was present in 14% of cases. All patients with biopsy diagnoses of CIN 1 had at least two previous abnormal Pap smears. Previous biopsy reports were available for review in 127 (12%) of the 1,103 patients. Of these 127 cases, 53.5% had a previous diagnosis of CIN/HPV; 9.4% had invasive carcinoma. A benign diagnosis was reported in 36.5%. CONCLUSION: The majority of BCC cases are due to reactive and inflammatory processes. In patients with a previous history of CIN, BCC may be of some significance. In patients with no significant prior cervical abnormalities, a Pap smear classified as BCC represents a reactive process.     

Bioinformatic analyses of microRNA-targeted genes and microarray-identified genes correlated with Barrett's esophagus

Barrett's esophagus (BE) is defined as a metaplasia condition in the distal esophagus, in which the native squamous epithelium lining is replaced by a columnar epithelium with or without intestinal metaplasia. It is commonly accepted that BE is a precancerous lesion for esophageal adenocarcinoma. The aim of this study was to investigate the aberrant microRNAs (miRNAs) and differentially expressed genes (DEGs) associated with BE based on online microarray datasets. One miRNA and five gene expression profiling datasets were retrieved from the Gene Expression Omnibus Database. Aberrant microRNAs and DEGs were obtained using R/Bioconductor statistical analysis language and software. 23 dysregulated miRNAs and 632 DEGs demonstrating consistent expression tendencies in the five gene microarrays were identified in BE. Moreover, 1962 target genes of aberrant miRNAs were predicted using three bioinformatic tools, namely TargetScan, RNA22-HSA and miRDB. Ultimately, 93 target DEGs were obtained, after which functional annotation was performed on DAVID Bioinformatics Resources. Among Gene Ontology (GO) biological processes, digestive tract development and epithelial cell differentiation have demonstrated significant associations with BE pathogenesis. In addition, analysis of the KEGG pathways has revealed associations with cancer. To enable further study, one miRNA-target DEGs regulatory network was constructed using Cytoscape. 6 target DEGs demonstrated higher-degree distributions in the network, and ROC analysis indicated that FNDC3B may be the best potential biomarker for BE diagnosis. The data presented herein may provide new perspectives for exploring BE pathogenesis and may offer hits with regard to potential biomarkers in BE diagnosis, prediction and therapeutic evaluation.     

Endometrial hyperplasia with berrylike squamous metaplasia and pilomatrixomalike shadow cells. Report of an intriguing cytohistologic case

BACKGROUND: The usefulness of endometrial cytology as a diagnostic method in asymptomatic women, especially in postmenopause, in the interpretation of composite pictures characterized by borderline features between atypical hyperplasia and well-differentiated adenocarcinoma, especially if associated metaplastic features are present, is somewhat controversial. CASE: An asymptomatic, 50-year-old, postmenopausal woman underwent a Pap smear and endometrial cytology for routine screening, disclosing three-dimensional, sometimes pseudopapillary groupings of hyperplastic endometrial glandular cells with focal atypia in direct continuity with large, squamoid cells of the keratinizing type and shadow cells. Histologic examination of endometrial tissue was advised, and two subsequent endometrial biopsies and hysteroscopic ablation were performed. The borderline character of the lesion (complex atypical hyperplasia vs. well-differentiated adenocarcinoma) with concomitant squamous metaplasia and pilomatrixomalike shadow cells prevented diagnostic agreement between several pathologists. CONCLUSION: Diagnostic cytology with direct endometrial sampling represents a valuable diagnostic screening tool for the differential diagnosis between normal and pathologic endometrium, a mucosal picture that deserves a subsequent (histologic) diagnostic procedure. In a few cases, as in the one presented above, even histologic examination, especially of so-called borderline lesions, reveals squamous or other types of metaplasia that can lead to interobserver discrepancies.     

Unilateral, multicentric Warthin's tumor mimicking a tumor metastatic to a lymph node. A case report

BACKGROUND: Warthin's tumor may be associated with false positive diagnoses of malignancy on fine needle aspiration. The most common cause of error is markedly atypical squamous metaplasia mimicking metastatic cystic squamous carcinoma. The common location of Warthin's tumors within periparotid nodes may add to the clinical suspicion of metastasis. We report a case of unilateral, multicentric Warthin's tumor arising in periparotid and intraparotid glands, leading to a strong clinical and cytologic suspicion of malignancy. CASE: A 60-year-old female presented with a 3-month history of several enlarged lymph nodes in the right side of the neck. Fine needle aspiration, performed at the right upper neck lymph node, suggested the possibility of metastatic tumor. On computed tomography and ultrasonography there were 4 nodular lesions in the right retromandibular area and lateral aspect of the neck, 1-1.5 cm in diameter. A thyroid scan revealed diffuse enlargement of the thyroid gland and a nodular lesion in the right lobe. Right thyroid lobectomy and modified radical neck dissection, including right superficial parotidectomy, were performed for evaluation of occult malignancy. Histologically we confirmed that the tumor was a synchronous, multicentric Warthin's tumor arising in the parotid gland and intraparotid and paraparotid lymph nodes. CONCLUSION: Clinicians and pathologists should consider an extraparotid Warthin's tumor in the differential diagnosis of multiple cervical masses.     

P16INK4A as an adjunct test in liquid-based cytology

OBJECTIVE: To assess the utility of P16INK4A as an adjunct test in liquid-based cytology in cases with equivocal morphologic changes of high grade squamous intraepithelial lesion (HSIL). STUDY DESIGN: P16INK4A immunoreactivity was investigated in residual ThinPrep material (Cytyc Corp., Boxborough, Massachusetts, U.S.A.) from 30 cases with equivocal diagnoses of HSIL that had corresponding follow-up biopsies. Two control ThinPrep cases were included: 1 HSIL with biopsy-confirmed cervical intraepithelial neoplasia (CIN) 3 and a negative specimen with a corresponding biopsy of squamous metaplasia. The expression of P16INK4A in ThinPrep specimens and corresponding biopsies was scored as previously described. A ThinPrep case was scored positive if it contained > 10 abnormal cells with nuclear and cytoplasmic immunocytochemical staining. Corresponding biopsies were scored as having negative, sporadic, focal or diffuse staining. RESULTS: The P16INK4A antibody assay was positive in 19 of 30 ThinPrep cases (63.3%). Seventeen of the 19 (89.4%) biopsies corresponding to the positively stained ThinPreps also were positive, with a score of at least focal positivity in the dysplastic regions (2 CIN 1, 4 CIN 2, 11 CIN 3; 2 lesions lost in the tissue recut). The assay was negative in 11 ThinPreps (36.6%) and 10 biopsies (33.3%) with tissue confirmation of chronic cervicitis (5), squamous metaplasia (2), CIN 1 (3) and 1 lesion lost in the tissue recut. Seventeen of 18 (94.4%) ThinPreps confirmed as high grade lesions upon biopsy showed P16INK4A positivity. The control HSIL case with a CIN 3 biopsy was diffusely positive for P16INK4A, and the control negative case with biopsy diagnosis of squamous metaplasia was negative. Nondysplastic squamous and metaplastic epithelium in 7 biopsies and nondysplastic squamous or metaplastic cells in ThinPrep cases were negative. Sporadic staining of bacteria, inflammatory cells and endocervical cells was noted. CONCLUSION: ThinPrep cases in the equivocal cytologic category with the corresponding tissue biopsy assayed for P16INK4A expression showed that there was utility for this type of testing. A larger series comparing corresponding ThinPrep and tissue biopsies will be undertaken. The role of HPV infection in these cases will also be explored.     

p53 and the malignant progression of Barrett's esophagus

Barrett's esophagus (BE) is a metaplastic disorder in which specialized columnar epithelium replaces healthy squamous epithelium (intestinal metaplasia). Even though its pathophysiology and the steps of its neoplastic progression are not completely understood, BE can be considered as a complication of gastroesophageal reflux disease (GERD). Given that esophageal adenocarcinoma, which is continually increasing in the Western world, still has a poor prognosis and suffers from late diagnosis, and because BE is a precancerous lesion, there is a strong need for good molecular markers of malignant progression in Barrett's metaplasia (BM). The aim of this review is to examine the published data regarding the role that assessment of p53 may play in the management of BE, trying to understand if it may be a useful marker to early diagnose BE malignant transformation.     

Enhancement of Squamous Cell Development in Cultured Skin by Cyclic Adenine Nucleotide and Prostaglandins

The present study tests the hypothesis that agents known to elevate the level of intracellular cyclic adenine nucleotide may direct different epithelial cells onto a pathway of epidermoid (squamous) development and differentiation. We report here that the mixture of dibutyryl cyclic AMP (dbcAMP), prostaglandins E₁, E₂ and B₁, (PG E₁, E₂, B₁), and papaverine (pap) enhances the rate of normal squamous cell development in organ-cultured skin of chick embryos. The three components may act synergistically to elevate the level of intracellular cyclic adenine nucleotide. We recently reported that the same group of agents induces abnormal development (squamous metaplasia) and aberrant differentiation (keratin production) in the normally cuboidal epithelium of cultured whole mammary glands of mice [1]. Thus, dbcAMP, PG E₁, E₂, B₁, and pap are effective in enhancing normal squamous cell development and also in inducing squamous metaplasia de novo in the epithelial components of two different organs of embryonic and adult animals of two classes of vertebrates. The combined findings are suggestive that cyclic adenine nucleotide together with the prostaglandins may act generally on diverse types of epithelia to bring about squamous cell development and a differentiation marked by keratin production.     

Aspiration cytology of the conjunctival surface

OBJECTIVE: To evaluate a method of obtaining conjunctival cells that utilizes aspiration of the conjunctival surface. STUDY DESIGN: Eighteen eyes from 16 patients with epibulbar lesions underwent aspiration of the conjunctival surface using a tuberculin syringe without a needle. The aspirated cells were prepared by the cytocentrifuge or Millipore filter technique. The lesions were subsequently biopsied, and the cytologic and histologic diagnoses were compared. RESULTS: Diagnoses of the conjunctival lesions, in decreasing order of frequency, were conjunctival intraepithelial neoplasia (dysplasia, carcinoma in situ), squamous cell carcinoma, squamous metaplasia, nevus, lymphoma and inflammation. In this feasibility study, the cytologic diagnosis accurately correlated with the histologic diagnosis in most cases. There were two cases in which the cytologic diagnosis led to the correct histologic diagnosis. CONCLUSION: Aspiration cytology of the conjunctival surface is useful in obtaining diagnostic material and may be used as a guide to where a biopsy should be performed. Limitations include inadequate samples and lack of observer experience.     

Roundness of epithelial nuclei in bronchial mucosa

OBJECTIVE: To estimate the shape of epithelial nuclei in bronchial mucosa. STUDY DESIGN: Bronchoscopic mucosal samples from 12 patients with chronic bronchitis and 14 patients with squamous cell bronchial carcinoma were routinely processed and stained with the hematoxylin and eosin method. Fields with stratification and squamous metaplasia were selected. The roundness of epithelial nuclei was estimated using Lucia, version 3.51 ab, with an objective of 40:1 (NA = 0.65) and final magnification of 1,900:1. The images were manually edited. Roundness was calculated from area and perimeter. RESULTS: The mean roundness in stratification and squamous metaplasia in bronchial mucosa from carcinoma patients (0.90 +/- 0.04) was significantly greater than in bronchial mucosa from chronic bronchitis patients (0.80 +/- 0.006) (P < .05). CONCLUSION: Our results indicate that cell nuclei in stratification and squamous metaplasia in patients without bronchial cancer are more elongated than nuclei found under the same conditions in patients with squamous cell carcinoma.     

Exfoliative cytology of atypical polypoid adenomyoma. A case report.

BACKGROUND: An atypical polypoid adenomyoma (APA) is a well-defined entity. It occurs in the endometrium, lower uterine segment and endocervix. It is usually composed of atypical complex glands with squamous metaplasia admixed with myofibromatous stroma. CASE: A 35-year-old female presented with one-year history of irregular menstrual periods. A diagnosis of adenocarcinoma in situ was rendered on her cervicovaginal smear. Pelvic examination revealed an enlarged uterus due to a leiomyoma. Colposcopic examination revealed a 0.6-cm, sessile, polypoid mass at the junction of the endocervix and ectocervix. A cone biopsy of the lesion showed irregular, endometrial-type glands embedded in a prominent myofibromatous stroma. The atypical glandular component of the mass demonstrated varying degrees of architectural complexity, ranging from simple to complex hyperplasia. In tissue sections the lesion was diagnosed as APA of the cervix. The patient underwent a hysterectomy for the leiomyoma. The hysterectomy specimen showed an 8.5-cm leiomyoma. The cervix and uterine corpus revealed no residual APA. CONCLUSION: APA of the cervix should be considered among the differential diagnoses of atypical glandular cells of undetermined significance. The diagnosis of APA cannot be made on cytology; the final diagnosis requires histologic confirmation.     

Clinical significance of a cytologic diagnosis of atypical glandular cells, favor endometrial origin, in Pap smears

OBJECTIVE: To evaluate the significance of a diagnosis of atypical glandular cells, favor endometrial origin (AGC-EM), using cytohistologic correlation. STUDY DESIGN: A retrospective search identified 90 cervicovaginal smears (vaginal pool) with a diagnosis of AGC-EM, in 2 tertiary care medical centers between January 1998 and December 2002. RESULTS: Forty-six (51%) were conventional preparations and 44 (49%) were liquid-based monolayers (SurePath, TriPath Imaging Inc., Burlington, North Carolina, U.S.A.). Follow-up biopsies were available in 55 of 90 (61%) cases, 15 of 90 (17%) cases had cytology follow-up, and 20 of 90 (22%) were lost to follow-up. The patients ranged in age from 30 to 86 years (mean, 56); 56 of 90 (62%) were > 50 years. Among the patients who underwent biopsy, 22 (40%) had a clinically significant lesion, including 10 (18%) endometrial adenocarcinomas, 8 (15%) endometrial hyperplasias and 4 (7%) high grade squamous intraepithelial lesion/squamous cell carcinoma, nonkeratinizing type. The remaining 33 patients had benign histology, including benign endometrium, endometrial polyp, tubal metaplasia, cystic endometrial atrophy and cervical microglandular hyperplasia. Of the patients with cytologic follow-up, 2 had Pap smears showing atypical squamous cells of undetermined significance, while the remainder had negative results. CONCLUSION: In our study population, 40% (22 of 55) of women who underwent biopsy following a diagnosis of AGC-EM had significant uterine lesions, with the majority of the lesions endometrial in origin. Patients with a diagnosis of AGC-EM, especially those > 50, should be followed closely, and endometrial sampling should be included in their initial workup.