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1.
Semin Diagn Pathol ; 39(3): 176-186, 2022 May.
Article in English | MEDLINE | ID: mdl-34852949

ABSTRACT

High-grade endometrial carcinoma (HGEC) is a heterogeneous group of tumors with various morphologic, genetic, and clinical characteristics. Morphologically, HGEC includes high-grade endometrioid carcinoma, serous carcinoma, clear cell carcinoma, undifferentiated/dedifferentiated carcinoma, and carcinosarcoma. The morphologic classification has been used for prognostication and treatment decisions. However, patient management based on morphologic classification is limited by suboptimal interobserver reproducibility, variable clinical outcomes observed within the same histotype, and frequent discordant histotyping/grading between biopsy and hysterectomy specimens. Recent studies from The Cancer Genome Atlas (TCGA) Research Network established four distinct molecular subtypes: POLE-ultramutated, microsatellite unstable, copy number high, and copy number low groups. Compared to histotyping, the TCGA molecular classification appears superior in risk stratification. The best prognosis is seen in the POLE-ultramutated group and the worst in copy number high group, while the prognosis in the microsatellite unstable and copy number low groups is in between. The TCGA subtyping is more reproducible and shows a better concordance between endometrial biopsy and resection specimens. It has now become apparent that the molecular classification can supplement histotyping in patient management. This article provides an overview of the pathologic diagnosis/differential diagnosis of HGEC and the TCGA classification of endometrial cancers, with the clinical significance and applications of TCGA classification briefly discussed when appropriate.


Subject(s)
Adenocarcinoma, Clear Cell , Carcinoma, Endometrioid , Endometrial Neoplasms , Biomarkers, Tumor/genetics , Carcinoma, Endometrioid/genetics , Carcinoma, Endometrioid/pathology , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Endometrial Neoplasms/surgery , Female , Humans , Mutation , Prognosis , Reproducibility of Results
2.
Int J Surg Pathol ; 31(3): 338-342, 2023 May.
Article in English | MEDLINE | ID: mdl-35708000

ABSTRACT

This was a 57-year-old woman who presented with mild discomfort in the right groin. Physical examination revealed a mass in the right groin, and by ultrasound, the mass was hypoechoic and solid with some internal vascularity. The clinical differential diagnosis included lymphoma and others. The mass was excised for pathologic evaluation. Gross examination of the specimen revealed a 3 × 2.4 × 2 cm, solid and cystic mass. Microscopically, it was a biphasic tumor consisting of carcinomatous and sarcomatous components. The tumor was seen contiguous with endometriosis and atypical endometrioid hyperplasia. The histologic findings were consistent with malignant mixed Mullerian tumor (MMMT) arising from endometriosis in the right groin. The tumor involved the resection margin. Subsequent chest/abdominal/pelvic computed tomography did not reveal evidence of tumors, and diagnostic peritoneal/pelvic laparoscopy did not show diseases. Postoperatively, the patient received 6 cycles of chemotherapy consisting of carboplatin and paclitaxel, followed by radiation in the right groin. Malignant transformation from endometriosis occurs in less than 1% of endometriosis cases, and about 80% of the transformed tumors occur in the ovaries. The most commonly transformed malignant tumors are endometrioid and clear cell carcinomas, with rare adenosarcoma and endometrial stromal sarcoma reported. To our knowledge, we are reporting the first case of MMMT arising from endometriosis in the groin.


Subject(s)
Adenosarcoma , Endometriosis , Mixed Tumor, Mullerian , Female , Humans , Middle Aged , Groin/pathology , Endometriosis/pathology , Adenosarcoma/diagnosis , Adenosarcoma/pathology , Adenosarcoma/surgery , Pelvis/pathology
3.
Mod Pathol ; 24(9): 1254-61, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21572399

ABSTRACT

Tubal metaplasia of the endometrium may occasionally display cytologic atypia (atypical tubal metaplasia) resembling serous carcinoma or endometrial intraepithelial carcinoma. Although atypical tubal metaplasia is presumed to be reactive or degenerative in etiology, its clinical significance is unknown. In this study, we investigated atypical tubal metaplasia in regard to its immunoexpression of p53, Ki-67, and human telomerase reverse transcriptase (TERT), and its long-term clinical outcome. A total of 63 cases of atypical tubal metaplasia and 200 cases of endometrial samples with typical tubal metaplasia were followed for a mean of 64 and 61 months, respectively. Of the 63 atypical tubal metaplasia cases, formalin-fixed, paraffin-embedded tissue sections from 16 cases were immunostained with antibodies to p53, Ki-67, and TERT. Sections from 13 cases of uterine serous carcinoma were also stained for TERT as control. After long-term follow-up, 5% of patients in the atypical tubal metaplasia group developed hyperplasia without atypia compared with 4% of patients in the control group (P=0.44), whereas 3% in the atypical tubal metaplasia group developed atypical hyperplasia or carcinoma compared with 2% in the control group (P=0.44). p53 immunoreactivity was either focal and weak or negative in all cases of both atypical and typical tubal metaplasia (P>0.05). Ki-67 immunoreactivity was present in 0-5% of cells in 94% of both atypical and typical tubal metaplasia (P>0.05). TERT immunoexpression was absent in all 16 cases of atypical tubal metaplasia, but present in all 13 cases of uterine serous carcinoma (P<0.0001). Our study indicates that atypical tubal metaplasia displays an immunostaining pattern similar to otherwise typical tubal metaplasia of the endometrium, and distinct from uterine serous neoplasms. The presence of atypical tubal metaplasia in endometrial samplings does not increase the risk of developing endometrial hyperplasia or malignancy.


Subject(s)
Biomarkers/analysis , Endometrium/pathology , Ki-67 Antigen/analysis , Telomerase/analysis , Tumor Suppressor Protein p53/analysis , Adult , Aged , Aged, 80 and over , Endometrium/metabolism , Female , Follow-Up Studies , Humans , Metaplasia , Middle Aged , Uterine Diseases/metabolism , Uterine Diseases/pathology , Young Adult
4.
Int J Surg Pathol ; 29(7): 716-721, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33881947

ABSTRACT

The literature shows a wide range in the frequencies of finding breast carcinoma in the excised specimens following a biopsy diagnosis of atypical ductal hyperplasia (ADH), likely due to a poor diagnostic reproducibility among different pathologists as well as an inherent heterogeneity in ADH. We evaluated whether histologic subtyping of ADH would help predict the risk of breast carcinoma. Our study consisted of 143 cases of ADH diagnosed by core needle biopsy and followed by excision. Of these, 54 cases (37.8%) showed carcinoma in the excised specimens (47 cases of ductal carcinoma in situ alone, 3 cases of invasive ductal carcinoma alone, and 4 cases of mixed invasive ductal carcinoma and ductal carcinoma in situ). We arbitrarily divided ADH into two subtypes: type A was considered when one or more ducts were completely replaced by low-grade ductal carcinoma in situ type cells but the lesion was <2 mm and type B was considered when one or more ducts were partially involved by low-grade ductal carcinoma in situ type cells regardless of lesion size. Type A was associated with a significantly higher frequency of breast carcinoma (63.6%) than type B (30.0%). ADH containing punctate necrosis showed a higher association of carcinoma (66.7%) compared to those without necrosis (35.1%). Within type B ADH, involvement of 3 or more foci had a higher frequency of carcinoma (50.0%) than involvement of fewer foci (26.6%). These histologic features of ADH may prove useful in predicting the likelihood of breast carcinoma and provide helpful information for patient's management.


Subject(s)
Breast Neoplasms/diagnosis , Carcinoma, Ductal, Breast/diagnosis , Carcinoma, Intraductal, Noninfiltrating/diagnosis , Mammary Glands, Human/pathology , Mastectomy, Segmental/statistics & numerical data , Adult , Aged , Aged, 80 and over , Biopsy, Large-Core Needle/statistics & numerical data , Breast Neoplasms/epidemiology , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/epidemiology , Carcinoma, Ductal, Breast/pathology , Carcinoma, Ductal, Breast/surgery , Carcinoma, Intraductal, Noninfiltrating/epidemiology , Carcinoma, Intraductal, Noninfiltrating/pathology , Carcinoma, Intraductal, Noninfiltrating/surgery , Female , Humans , Hyperplasia/diagnosis , Hyperplasia/pathology , Hyperplasia/surgery , Mammary Glands, Human/surgery , Middle Aged , Necrosis/diagnosis , Necrosis/pathology , Necrosis/surgery , Prognosis , Reproducibility of Results , Risk Assessment/methods , Risk Assessment/statistics & numerical data
5.
Case Rep Hematol ; 2019: 5718716, 2019.
Article in English | MEDLINE | ID: mdl-31781425

ABSTRACT

Amoxicillin/clavulanic acid is one of the widely prescribed antibiotics in the outpatient setting giving excellent antimicrobial coverage and relatively safe profile in terms of adverse reactions. Gastrointestinal and cutaneous reactions are among the commonly reported. Our goal is to describe a case of agranulocytosis induced by amoxicillin/clavulanic acid in a previously healthy patient and review prior reports with similar presentation.

6.
Hum Pathol ; 80: 40-46, 2018 10.
Article in English | MEDLINE | ID: mdl-29559235

ABSTRACT

There is a wide range of finding endometrial adenocarcinoma (ADCA) in the uterus after a diagnosis of complex atypical hyperplasia (CAH), likely due to a poor diagnostic reproducibility and an inherent heterogeneity in CAH. We evaluated whether histologic subtyping of CAH would help predict ADCA. Our study consisted of 222 cases of CAH diagnosed by endometrial biopsy or curettage. ADCA was seen in 38.3% of these cases at hysterectomy. We divided CAH into 2 subtypes: type A was defined as back-to-back glands in a focus smaller than 2.1 mm, and type B as crowded glands with cytologic atypia but with still-intervening stroma regardless of lesional size. Type A was associated with a significantly higher frequency of ADCA (75.9%) compared with type B (26.2%). Lesions containing neutrophilic/cellular debris showed a higher association of ADCA (60.0%) compared with those without neutrophilic/cellular debris (35.5%). CAH present outside endometrial polyp was associated with a higher frequency of ADCA (42.5%) than that confined to endometrial polyp (19.5%). Within type B cases, lesions greater than 3 mm had a higher association of ADCA (34.3%) than did smaller ones (13.6%). Patients older than 50 years were more likely to have ADCA in the uterus compared with younger women with a preoperative diagnosis of CAH (43.2% versus 28.3%). CAH made on office biopsy showed a higher association of ADCA (46.6%) compared with a diagnosis made on curettage (31.1%). Recognition of these clinicopathological features in CAH may prove useful in predicting the likelihood of ADCA in the uterus.


Subject(s)
Endometrial Hyperplasia/pathology , Endometrial Neoplasms/pathology , Endometrium/pathology , Hyperplasia/pathology , Adenocarcinoma/pathology , Adult , Aged , Female , Humans , Male , Middle Aged , Precancerous Conditions/pathology , Uterine Neoplasms/pathology
7.
Hum Pathol ; 59: 120-124, 2017 01.
Article in English | MEDLINE | ID: mdl-27746268

ABSTRACT

Ovarian hyperthecosis, a source of estrogen, may occur in postmenopausal women. In this study, we evaluated the possible association of ovarian hyperthecosis with endometrial polyp, endometrial hyperplasia, and endometrioid adenocarcinoma in postmenopausal women. Our study consisted of 238 postmenopausal women: 108 with endometrioid adenocarcinoma and 130 without endometrial carcinoma. The International Federation of Gynecology and Obstetrics system was used to grade endometrioid adenocarcinoma. Within the endometrioid adenocarcinoma cases, 48 (44.4%) were grade 1, 46 (42.6%) were grade 2, and 14 (13.0%) were grade 3. Among the noncancer cases, 71 (54.6%) had atrophic endometrium, 32 (24.6%) had endometrial polyp, and 27 (20.8%) had endometrial hyperplasia. The frequency of ovarian hyperthecosis in patients with endometrial polyp (46.9%), endometrial hyperplasia (55.6%), and grade 1 (43.8%), grade 2 (54.3%), and grade 3 (57.1%) endometrioid adenocarcinoma was each significantly higher than that in patients with atrophic endometrium (23.9%), supporting an association of these lesions with ovarian hyperthecosis in postmenopausal women. There was no statistically significant difference in the rate of ovarian hyperthecosis among patients with endometrial polyp, endometrial hyperplasia, and grade 1, grade 2, and grade 3 endometrioid adenocarcinoma. Our study indicates that ovarian hyperthecosis with its resultant risk factor of hyperestrinism may contribute to the pathogenesis of endometrial polyp, endometrial hyperplasia, and endometrioid adenocarcinoma in postmenopausal women. Although some studies show that grade 3 endometrioid adenocarcinoma has different genetic/molecular changes from its lower-grade counterparts, our study suggests that endometrioid adenocarcinoma of all grades may share the common risk factor of hyperestrinism.


Subject(s)
Carcinoma, Endometrioid/pathology , Endometrial Hyperplasia/pathology , Endometrial Neoplasms/pathology , Endometrium/pathology , Ovary/pathology , Polyps/pathology , Postmenopause , Biopsy , Carcinoma, Endometrioid/surgery , Case-Control Studies , Endometrial Hyperplasia/surgery , Endometrial Neoplasms/surgery , Endometrium/surgery , Female , Humans , Hysterectomy , Middle Aged , Neoplasm Grading , Polyps/surgery
8.
Acta Cytol ; 61(3): 194-198, 2017.
Article in English | MEDLINE | ID: mdl-28486237

ABSTRACT

OBJECTIVE: The 2014 Bethesda System recommends that benign-appearing endometrial cells (BECs) in routine Pap tests should be reported in patients aged ≥45 years. This is a change from previous guidelines to report BECs in women ≥40 years of age. BECs are reported to have 1% chance of endometrial lesion on follow-up. This study tests whether the new threshold may increase the specificity of the test for the detection of clinically significant endometrial lesions. STUDY DESIGN: After institutional review board approval, 1,177 BECs, reported during an 8-year study period in patients aged ≥40 years, were retrieved from 672,000 routine ThinPrep Pap tests. The results of subsequent workup were collected by chart review, and the Fisher exact test was used to compare results in patients aged <50 and ≥50 years. RESULTS: No endometrial carcinoma and only 2 cases of endometrial hyperplasia were detected in women aged <50 years, whereas 5.5% of women aged ≥50 years with BECs had carcinoma and/or endometrial hyperplasia (p = 0.000169). CONCLUSION: Investigation of BECs on routine Pap test are useful in patients aged ≥50 years as 5.5% of cases were confirmed to have significant endometrial disease. Our data as well as other studies support raising the BEC-reporting age threshold from ≥45 to ≥50 years, as the new threshold may improve the specificity of the test.


Subject(s)
Endometrium/pathology , Papanicolaou Test/methods , Adult , Age Factors , Biopsy , Female , Humans , Hysterectomy , Middle Aged , Retrospective Studies
9.
Hum Pathol ; 37(10): 1350-6, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16949924

ABSTRACT

Uterine leiomyomas (LMs) and leiomyosarcomas (LMSs), both of smooth muscle origin, sometimes coexist in the same uterus. Little genetic evidence exists concerning the developmental relationship between LM and LMS. Using the X-chromosome inactivation pattern of the human androgen receptor gene, we examined the clonality of LM and LMS. Of the 24 patients with LM, 21 had multiple neoplasms; all were clonal and individual LMs derived from separate clones. Of the 20 patients with LMS, 6 exhibited multiple tumors in the uterus, and 4 of these individuals also harbored coexisting uterine LMs. We found all LMSs to be clonal. Separate tumors showed identical pattern of X inactivation in 4 patients, and in 2 other individuals, multiple LMSs developed from independent clones. Among the 4 patients with LMS and coexisting LM, 3 showed the same pattern of X inactivation in LMS and the adjacent LM. In 2 of the 3 patients, the tumor also exhibited a morphological transition between benign cells in LM and malignant cells in LMS, supporting the possibility of transformation from LM to LMS. One patient displayed different clones in LMS and the coexisting LM, indicating their independent origins. We conclude that (i) both LM and LMS are clonal; (ii) different nodules in multiple LM are of independent origins; (iii) multiple lesions of LMS may be either monoclonal or multiclonal; (iv) most LMSs are solitary lesions and are most likely de novo, but an individual LM may undergo "malignant transformation" to a LMS; and (v) some LMSs and coexisting LMs are of independent origins.


Subject(s)
Chromosomes, Human, X , Leiomyoma/genetics , Leiomyosarcoma/genetics , Uterine Neoplasms/genetics , X Chromosome Inactivation , Adult , Clone Cells , DNA, Neoplasm/analysis , Female , Humans , Leiomyoma/pathology , Leiomyosarcoma/pathology , Middle Aged , Polymerase Chain Reaction , Receptors, Androgen/genetics , Uterine Neoplasms/pathology
10.
Breast Cancer ; 12(4): 294-8, 2005.
Article in English | MEDLINE | ID: mdl-16286910

ABSTRACT

Clinical studies have shown a correlation of HER-2/neu amplification/over-expression and favorable response to neoadjuvant chemotherapy and anti-HER-2/neu antibody treatment. However, contradictory findings also have been reported. Some tumors may develop resistance to neoadjuvant chemotherapy after an initial period of sensitivity. Our study attempts to evaluate the effects of neoadjuvant chemotherapy on HER-2/neu status in locally advanced breast cancer. Thirty-nine patients with locally advanced breast cancers established by core needle biopsy received neoadjuvant chemotherapy and were compared with 60 patients with breast cancers who did not receive neoadjuvant chemotherapy. IHC for HER-2/neu was performed on paraffin sections of the core biopsy before treatment and the excised specimen following chemotherapy and scored as Negative (0-1+), 2+ and 3+. The results of the study and the controls were compared and analyzed using Fisher's exact test. HER-2/neu IHC scores decreased in 28.5% (15/39) of patients receiving neo-adjuvant chemotherapy compared to 11.7% (7/60) of patients in the control (p < 0.013). HER-2/neu IHC status changed from strongly positive to negative (3+ to 0) in five of 39 (12.5%) in the study group and in 2 of 60 (3.3%) in control group (p = 0.104). For patients receiving neoadjuvant chemotherapy in whom the tumor becomes refractory to chemotherapy or recurs, repeat testing for HER-2/neu status may be necessary. Elimination of HER-2/neu positive tumor cells may account for the changes in the IHC scores and the development of resistance to neoadjuvant chemotherapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Carcinoma/drug therapy , Gene Expression Profiling , Receptor, ErbB-2/biosynthesis , Breast Neoplasms/genetics , Breast Neoplasms/surgery , Carcinoma/genetics , Carcinoma/surgery , Case-Control Studies , Drug Resistance, Neoplasm , Female , Humans , Neoadjuvant Therapy , Treatment Outcome
11.
J Reprod Med ; 50(8): 643-6, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16220776

ABSTRACT

BACKGROUND: Benign endocervical-type mucinous adenomyoma arising in the uterine corpus is a rare entity. We report a case of intraepithelial mucinous adenocarcinoma arising in an endocervical-type mucinous adenomyoma of the uterine corpus in a previously healthy woman. CASE: A 55-year-old, white woman presented with postmenopausal bleeding. Uterine leiomyomas and endometrial polyps were suggested by ultrasonography. Endometrial curettage showed multiple polypoid tissue fragments, each composed of glands lined with tall columnar endocervical-type mucinous epithelium lying within a background of endometrial-type stroma and smooth muscle fibers. The mucinous glandular epithelium showed a spectrum of architectural and cytologic changes ranging from benign to severe atypia and occasional back-to-back cribriform glands, consistent with adenocarcinoma. The surrounding smooth muscle fibers and endometrial stromal cells were benign. A diagnosis was made of intraepithelial adenocarcinoma arising in a mucinous adenomyoma in the uterine corpus. CONCLUSION: Endocervical-type mucinous adenomyoma, although previously reported as a benign entity, may contain areas of adenocarcinoma.


Subject(s)
Adenocarcinoma, Mucinous/diagnosis , Adenomyoma/diagnosis , Neoplasms, Second Primary/diagnosis , Uterine Neoplasms/diagnosis , Adenocarcinoma, Mucinous/pathology , Adenocarcinoma, Mucinous/surgery , Adenomyoma/pathology , Adenomyoma/surgery , Diagnosis, Differential , Endometrium/pathology , Epithelium/pathology , Female , Humans , Hysterectomy , In Situ Hybridization , Middle Aged , Muscle, Smooth/pathology , Neoplasms, Second Primary/pathology , Neoplasms, Second Primary/surgery , Polyps/diagnosis , Polyps/pathology , Polyps/surgery , Treatment Outcome , Uterine Hemorrhage/diagnosis , Uterine Hemorrhage/etiology , Uterine Hemorrhage/pathology , Uterine Neoplasms/pathology , Uterine Neoplasms/surgery
12.
Hum Pathol ; 46(9): 1376-81, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26220161

ABSTRACT

High-risk human papillomavirus infection usually is seen at one anatomic site in an individual. Rarely, infection at multiple anatomic sites of the female lower genital tract in the same individual is encountered either simultaneously and/or at a later date. The current study identifies the various subtypes of high-risk human papillomavirus infection in these scenarios and analyzes the potential significance of these findings. High-risk human papillomavirus infection involving 22 anatomic sites from 7 individuals was identified after institutional review board approval. Residual paraffin-embedded tissue samples were retrieved, and all 15 high-risk human papillomavirus were identified and viral load quantified using multiplex real-time polymerase chain reaction-based method. Multiple high-risk human papillomavirus subtypes were identified in 32% of the samples and as many as 5 different subtypes of high-risk human papillomavirus infection in a single anatomic site. In general, each anatomic site has unique combination of viral subtypes, although one individual showed overlapping subtypes in the vagina, cervix, and vulvar samples. Higher viral load and rare subtypes are more frequent in younger patients and in dysplasia compared with carcinoma. Follow-up ranging from 3 to 84 months revealed persistent high-risk human papillomavirus infection in 60% of cases.


Subject(s)
DNA, Viral/genetics , Genital Neoplasms, Female/diagnosis , Human Papillomavirus DNA Tests , Multiplex Polymerase Chain Reaction , Papillomaviridae/genetics , Papillomavirus Infections/diagnosis , Real-Time Polymerase Chain Reaction , Adult , Aged , Aged, 80 and over , Female , Genital Neoplasms, Female/pathology , Genital Neoplasms, Female/virology , Humans , Middle Aged , Papillomavirus Infections/pathology , Papillomavirus Infections/virology , Predictive Value of Tests , Prognosis , Risk Assessment , Risk Factors , Time Factors , Viral Load , Young Adult
13.
Hum Pathol ; 34(9): 880-5, 2003 Sep.
Article in English | MEDLINE | ID: mdl-14562283

ABSTRACT

Molecular alterations that are associated with clinicopathological features of extramammary Paget's disease of the vulva (PDV) are poorly understood. Consequently, we have investigated whether a correlation exists between overexpression of p53 protein and various clinicopathologic features of PDV. Our study group comprises 10 primary noninvasive PDVs, 3 primary PDVs with minimal invasion, and 1 primary PDV with frank invasion. Recurrence in the form of noninvasive PDV was seen in 4 patients with previously noninvasive PDVs and in 1 patient who previously had PDV with minimal invasion. Metastases to the inguinal lymph nodes were associated with the 1 PDV with frank invasion and 1 of the PDVs with minimal invasion. An immunohistochemical study of p53 expression was performed on paraffin-embedded tissue. Negative p53 immunostaining was seen in all of the primary noninvasive PDVs as well as their recurrences. Positive p53 immunostaining was observed in the invasive as well as the intraepidermal components of all of the primary PDVs with invasion, the metastatic tumors in the inguinal lymph nodes, and the recurrent PDV associated with prior invasion, indicating a possible role of p53 in the progression of PDV. To our knowledge, our observation of p53 overexpression in the intraepidermal component of PDVs associated with invasion is the first to be reported in the literature. This observation may prove helpful in identifying stromal invasion in small biopsies. We also report for the first time an association between high nuclear grade in PDV and the propensity for inguinal lymph node metastasis.


Subject(s)
Paget Disease, Extramammary/metabolism , Tumor Suppressor Protein p53/metabolism , Vulvar Neoplasms/metabolism , Aged , Aged, 80 and over , Female , Fluorescent Antibody Technique, Indirect , Humans , Lymph Nodes/pathology , Middle Aged , Neoplasm Invasiveness , Neoplasm Recurrence, Local , Paget Disease, Extramammary/secondary , Paget Disease, Extramammary/surgery , Stromal Cells/pathology , Vulvar Neoplasms/pathology , Vulvar Neoplasms/surgery
14.
J Reprod Med ; 49(6): 457-62, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15283054

ABSTRACT

OBJECTIVE: To assess the utility of consensus review of original ThinPrep slides (Cytyc Corp., Boxborough, Masssachusetts) vs. duplicate slides and to identify the significance of the number of representative cells in classifying atypical squamous metaplastic cells, cannot exclude high grade squamous intraepithelial lesion (ASC-H). STUDY DESIGN: A duplicate ThinPrep slide was prepared from 19 cases of ASC-H. Both original and duplicate slides underwent blinded review by 4 pathologists. Consensus cytologic interpretations (75% agreement) were noted and compared with follow-up diagnoses. Dots with atypical metaplastic cells from each slide were counted and correlated with the consensus cytologic interpretation. RESULTS: Following review of 19 original and 19 duplicate slides, consensus interpretations were reached in 14 and 15 cases, respectively. Nine cases of squamous intraepithelial lesion (SIL) were confirmed by biopsies. Consensus interpretation of original and duplicate slides predicted 7 and 6 cases of SIL, respectively. Consensus interpretation of duplicate slides predicted 60% of histologically benign cases. Two-thirds of nonconsensus cases were histologically benign. Consensus interpretations for high grade SIL were reached more often on slides with greater numbers of atypical squamous metaplastic cells. Fewer abnormal cells were present on the duplicate slides. CONCLUSION: Consensus reviews of original and duplicate slides are equally useful in classifying atypical squamous cells, cannot exclude high grade squamous intraepithelial lesion, but may not be practical in all circumstances. HPV DNA testing of all such cases may better detect clinically significant cases.


Subject(s)
Carcinoma, Squamous Cell/diagnosis , Microtomy , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Neoplasms/diagnosis , Adult , Carcinoma, Squamous Cell/pathology , Cervix Uteri/cytology , Female , Humans , Mass Screening , Observer Variation , Reproducibility of Results , Sensitivity and Specificity , Uterine Cervical Neoplasms/pathology , Vaginal Smears , Uterine Cervical Dysplasia/pathology
15.
Diagn Mol Pathol ; 22(1): 35-40, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23370429

ABSTRACT

The BRAF V600E somatic mutation is recognized as an oncogenic driver of many human cancers involving the MAPK/ERK pathway. Colorectal and lung cancers associated with the BRAF V600E mutation often demonstrated mucinous morphology. This study hypothesized that the BRAF V600E mutation may be associated with mucinous morphology in endometrial cancer and aimed to investigate its prevalence in mucinous (endometrial) carcinoma (MC) and endometrioid adenocarcinoma with significant mucinous differentiations (ECMD) (>10% neoplastic cells). Twenty-eight cases of endometrial cancer were selected, including 17 (60.7%) cases of MC or ECMD. All patients were Caucasian with age ranging from 50 to 87 years old (median 65). Genomic DNA was extracted from formalin-fixed paraffin-embedded tumor tissue and subjected to both real-time mutant allele-specific amplification polymerase chain reaction (PCR) and PCR amplification, followed by direct sequencing. Three (3/28, 10.7%) BRAF V600E mutations were detected by real-time mutant allele-specific amplification PCR and confirmed by direct sequencing. Two of 3 cases positive for BRAF V600E mutation were ECMDs with "surface epithelial changes." KRAS mutations were found in 9 cases (32.1%), none with BRAF mutation. This is the first report of BRAF V600E mutation in endometrial cancer, indicating that it may contribute to tumorigenesis of endometrial cancer, although at a low frequency compared with KRAS mutations.


Subject(s)
Adenocarcinoma/genetics , Adenocarcinoma/pathology , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Mutation, Missense , Proto-Oncogene Proteins B-raf/genetics , Adenocarcinoma, Mucinous/genetics , Adenocarcinoma, Mucinous/pathology , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Polymerase Chain Reaction , Sequence Analysis, DNA , Tissue Embedding
16.
Int J Surg Pathol ; 20(1): 97-100, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21427093

ABSTRACT

A 40-year-old woman underwent excision of a painless left vulvar mass. The specimen showed a well-circumscribed mass measuring 3.5 × 2.7 × 2.5 cm. Microscopic examination exhibited an encapsulated neoplasm with a solid and papillary growth pattern. The tumor cells were oval to columnar and showed moderate nuclear atypia. No capsular invasion was identified. Immunonegativity for calponin and p63 confirmed the absence of myoepithelial cells either within or at the periphery of the tumor. The tumor was immunopositive for gross cystic disease fluid protein 15, synaptophysin, and chromogranin. The histologic and immunohistochemical characteristics were consistent with an encapsulated solid papillary carcinoma with neuroendocrine differentiation. The patient has been free of disease for 4 years after surgery. This is the first report of a vulvar encapsulated solid papillary carcinoma with neuroendocrine differentiation. Correct diagnosis is imperative because of the distinct biologic behavior of the tumor.


Subject(s)
Carcinoma, Papillary/pathology , Vulvar Neoplasms/pathology , Adult , Carcinoma, Papillary/metabolism , Cell Differentiation , Female , Humans , Immunohistochemistry , Vulvar Neoplasms/metabolism
17.
Patholog Res Int ; 2012: 674748, 2012.
Article in English | MEDLINE | ID: mdl-23213623

ABSTRACT

UNLABELLED: Clear cell carcinomas (CCC) of the mullerian system are considered high grade tumors, but morphologically, the cells of CCC show both low and high grade features. The aims of the current study were to categorize CCC into low and high nuclear grade types, correlate their association with endometriosis, and then observe possible variations in pathogenesis based on their expression of p53 and Ki-67. We studied 41 pure mullerian CCCs and designated each as either a high (HNG) or low (LNG) nuclear grade tumor. Morphologically, 17 (41%) CCCs were LNG and 24 (59%) were HNG. Nine (38%) HNG and 2 (12%) LNG tumors showed positive immunostaining with p53. Endometriosis was associated with 8 (47%) LNG tumors and 8 (33%) HNG CCCs. Of the 11 cases with p53 alteration, 4 (1 LNG and 3 HNG) were associated with endometriosis. CONCLUSIONS: HNG CCCs, irrespective of their association with endometriosis, have alterations of p53. In general, LNG ovarian and endometrial CCCs, irrespective of their association with endometriosis/adenomyosis, are less likely to show p53 alteration. It appears that mullerian CCCs may have variable pathogenesis depending on their nuclear grade and association with endometriosis. A larger study is needed to validate these findings.

18.
Hum Pathol ; 43(5): 747-52, 2012 May.
Article in English | MEDLINE | ID: mdl-22047646

ABSTRACT

Serous borderline ovarian tumors have a favorable prognosis, and recurrences are uncommon. The factors influencing recurrence are not fully understood. Epithelial inclusions are identified in serous borderline ovarian tumors and are traditionally referred to as epithelial implants, which often show epithelial proliferation. We investigated whether the presence of epithelial implant and epithelial proliferation portends a higher risk for recurrence of serous borderline ovarian tumors in patients who underwent surgical removal of these tumors. Also examined was whether the anatomical site of epithelial implant and epithelial proliferation was associated with a higher risk of recurrence. One hundred eighty-eight cases of pure serous or predominantly serous borderline ovarian tumors were studied for the presence of epithelial implant and epithelial proliferation, and subsequent recurrences were recorded. The anatomical sites of epithelial implant and epithelial proliferation were compared between serous borderline ovarian tumors with or without recurrence. Statistical analysis was performed using the χ(2) test. Epithelial implant was noted in 106 cases (56%), and epithelial proliferation, in 26 cases (14%). Recurrence was identified in 10.4% cases with epithelial implant and 23% cases with epithelial proliferation. Statistical analyses of patients with recurrence showed significant differences in the following groups: epithelial implant versus no epithelial implant (P < .025) and epithelial proliferation versus no epithelial implant (P < .001). Recurrence rates were higher in the epithelial implant and epithelial proliferation groups as compared with no epithelial implant or epithelial proliferation groups. Epithelial implant and epithelial proliferation appear to pose a statistically significantly higher risk of recurrence in serous borderline ovarian tumors as compared with the absence of epithelial implant. Although the anatomical location of such implants was not significantly associated with a higher risk, the presence of epithelial proliferation at multiple sites was more frequently seen in recurrent serous borderline ovarian tumors.


Subject(s)
Cystadenoma, Serous/pathology , Epithelial Cells/pathology , Neoplasm Recurrence, Local/pathology , Ovarian Neoplasms/pathology , Adult , Cell Proliferation , Cystadenoma, Serous/surgery , Female , Follow-Up Studies , Humans , Ovarian Neoplasms/surgery , Prognosis , Risk
19.
Case Rep Pathol ; 2012: 418070, 2012.
Article in English | MEDLINE | ID: mdl-22953131

ABSTRACT

A 73-year-old woman was found to have a 1.7 cm axillary mass, for which a core needle biopsy was performed. The specimen revealed fragmented squamous epithelium surrounded by lymphoid tissue consistent with a squamous inclusion cyst in a lymph node, but a metastatic squamous cell carcinoma could not be excluded. Within one month, the lesion enlarged to 5 cm and was excised. Touch preparation cytology during intraoperative consultation displayed numerous single and sheets of atypical epithelioid cells with enlarged nuclei and occasional mitoses, suggesting a carcinoma. However, multinucleated giant cells and neutrophils in the background indicated reactive changes. We interpreted the touch preparation as atypical and recommended conservative surgical management. Permanent sections revealed a ruptured squamous inclusion cyst in a lymph node with extensive reactive changes. Retrospectively, the atypical epithelioid cells on touch preparation corresponded to reactive histiocytes. This is the first case report of a rapidly enlarging ruptured squamous inclusion cyst in an axillary lymph node following core needle biopsy. Our case demonstrates the diagnostic challenges related to a ruptured squamous inclusion cyst and serves to inform the readers to consider this lesion in the differential diagnosis for similar situations.

20.
Diagn Pathol ; 6: 3, 2011 Jan 10.
Article in English | MEDLINE | ID: mdl-21219622

ABSTRACT

We describe two cases of large solitary luteinized follicle cyst of pregnancy and puerperium (LSLFCPP) with new clinicopathologic findings. The first case occurred in a 40-year old woman who was found to have a left ovarian mass during the third trimester of pregnancy. The patient delivered a full term healthy female infant via caesarean section. The ovarian mass was removed by oophorectomy. The specimen showed a unilocular, thin-walled, clear fluid filled cyst measuring 15 × 12 × 5 cm. Microscopically, the cyst was lined by single to multiple layers of luteinized cells with mainly small, round and regular nuclei and focally enlarged, bizarre, and hyperchromatic nuclei. Occasional mitotic figures were seen. The cyst wall showed marked edema and nests of luteinized cells that were morphologically similar to the cyst lining cells. Groups of lesional cells were surrounded by reticulin fibers. The patient has been healthy without disease after 7 years. The second patient was a 29-year old pregnant woman who was found to have a right ovarian cyst by ultrasound at 14-week gestation. She then presented with preterm labor at 33-week gestation and delivered a healthy female infant via caesarean section. A right salpingo-oophorectomy was performed. Gross inspection of the specimen revealed a unilocular, brown mucoid fluid filled cyst measuring 14 × 11 × 9 cm. The cyst surfaces were smooth, and the cyst wall exhibited marked edema. Microscopic examination showed features similar to the first case: cyst lined by luteinized cells with focal large nuclei, scattered nests of luteinized cells in the edematous fibrous wall, and reticulin fibers surrounding large nests of lesional cells. No mitoses, however, were identified in the second case. The patient has been well without disease 1 year after surgery. These two cases contribute to a better understanding of LSLFCPP. Our case in the 40-year old patient is the first to show mitotic figures in LSLFCPP and suggests that the presence of occasional mitoses should not exclude a diagnosis of LSLFCPP. The lesion in the second patient caused preterm labor. Nevertheless, absence of disease recurrence in our patients demonstrates a benign nature of LSLFCPP.


Subject(s)
Follicular Cyst/diagnosis , Ovarian Cysts/diagnosis , Postpartum Period , Pregnancy Complications/diagnosis , Adult , Female , Follicular Cyst/pathology , Follicular Cyst/surgery , Humans , Mitotic Index , Ovarian Cysts/pathology , Ovarian Cysts/surgery , Ovariectomy , Pregnancy , Pregnancy Complications/pathology , Pregnancy Complications/surgery , Treatment Outcome
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