PLEKHA7, an Apical Adherens Junction Protein, Suppresses Inflammatory Breast Cancer in the Context of High E-Cadherin and p120-Catenin Expression.

Inflammatory breast cancer is a highly aggressive form of breast cancer that forms clusters of tumor emboli in dermal lymphatics and readily metastasizes. These cancers express high levels of E-cadherin, the major mediator of adherens junctions, which enhances formation of tumor emboli. Previous studies suggest that E-cadherin promotes cancer when the balance between apical and basolateral cadherin complexes is disrupted. Here, we used immunohistochemistry of inflammatory breast cancer patient samples and analysis of cell lines to determine the expression of PLEKHA7, an apical adherens junction protein. We used viral transduction to re-express PLEKHA7 in inflammatory breast cancer cells and examined their aggressiveness in 2D and 3D cultures and in vivo. We determined that PLEKHA7 was deregulated in inflammatory breast cancer, demonstrating improper localization or lost expression in most patient samples and very low expression in cell lines. Re-expressing PLEKHA7 suppressed proliferation, anchorage independent growth, spheroid viability, and tumor growth in vivo. The data indicate that PLEKHA7 is frequently deregulated and acts to suppress inflammatory breast cancer. The data also promote the need for future inquiry into the imbalance between apical and basolateral cadherin complexes as driving forces in inflammatory breast cancer.

Clinical Management of Mucocele-Like Lesions of the Breast with Limited or no Epithelial Atypia on Core Biopsy: Experience from Two Institutions.

PURPOSE: Mucocele-like lesions of the breast identified on core biopsy are rare high-risk lesions associated with variable upgrade rates to carcinoma on excision. We aimed to identify the clinicoradiopathological features that can help optimize management of this lesion. METHODS: We evaluated 50 mucocele-like lesions identified on core biopsies from two institutions, including 36 with no atypia and 14 with limited atypia. Outcome data from excision or clinicoradiological follow-up were reviewed with core biopsy results. RESULTS: Radiological targets were calcifications in 74% of cases, calcifications with associated mass or density in 16%, and mass in 10%. One of the 16 excised lesions without atypia on core biopsy, which was a mass lesion, was upgraded to mucinous carcinoma on excision. Of the 12 excised lesions with limited atypia, none were upgraded on excision. Among the lesions not excised, 20 without atypia had a median follow-up of 61 months, and 2 with limited atypia had follow-up of 97 and 109 months. None of these 22 patients had new development of their lesions on follow-up. The upgrade rate was 2% in our entire cohort, 3% for lesions without atypia, and 0% for lesions with limited atypia. CONCLUSIONS: Clinicoradiological surveillance can be appropriate when a mucocele-like lesion without atypia is identified on core biopsy for a non-mass lesion with pathological-radiological concordance. For mucocele-like lesions with limited atypia, a nonsurgical approach could be considered if the atypia by itself does not warrant excision. The latter recommendation requires careful clinicopathological correlation and support from additional studies.

Intermediate and long-term outcomes of fibroadenoma excision in adolescent and young adult patients.

Fibroadenomas are benign breast masses that often occur in adolescence and young adulthood. Primary management options include observation or surgical excision, but little is known about long-term outcomes after fibroadenoma excision in adolescents. In the present study, we reviewed the medical records of females aged 13-35 years who underwent fibroadenoma excision at our institution from 1986 through 2010. Patients were included if they had excision of at least 1 fibroadenoma (confirmed by histopathology) smaller than 5 cm in maximal diameter. We collected information pertaining to clinical presentation, management, and outcomes. In addition, an investigator-designed long-term outcome survey was sent to 138 eligible participants to assess patient satisfaction, as well as the recurrence of fibroadenoma, and the need or desire for further surgical intervention. Most patients (126 of 138) underwent 1 operation for fibroadenoma excision. Three women underwent immediate breast reconstruction at fibroadenoma excision. Fifty-seven patients completed the investigator-designed survey (response rate, 41.3%) with a median follow-up time of 13.5 (range, 2.0-26.7) years. Nine of 55 patients (16.4%) reported postoperative breast asymmetry and the desire to pursue reconstructive surgery. Three survey responders reported breast pain. Fourteen of 56 women (25.0%) reported the diagnosis of 1 or more additional fibroadenomas after the initial excision; another 7 reported recurrence of the mass at the site of excision. Most survey participants were satisfied with the aesthetic outcome of their fibroadenoma excision; however, a small proportion believed that they would benefit from reconstructive breast surgery. The recurrence and development of additional fibroadenomas should be addressed by providers during counseling for treatment options and postoperative follow-up.

Multivariate model to identify women at low risk of cancer upgrade after a core needle biopsy diagnosis of atypical ductal hyperplasia.

PURPOSE: Atypical ductal hyperplasia (ADH) identified on percutaneous breast biopsy represents a high-risk lesion, upgrading to cancer with surgical excision in ~7-45.8% of cases. Routine excision is questioned due to potential overtreatment and cost. This study evaluates clinical, imaging, and histologic features to predict the risk of upgrade. METHODS: With IRB approval, a single-institution retrospective review was performed of patients who underwent surgical excision of ADH diagnosed by core biopsy from June 2005 to June 2013. We reviewed electronic medical records, breast imaging, and biopsy slides. Multiple imputation was used for missing data. Association of various features with cancer upgrade was assessed using logistic regression. RESULTS: Among 399 cases, the upgrade rate to cancer was 16.0%, (95% CI: 12.8-20.0%), with nine invasive cancers and 55 ductal carcinoma in situ (DCIS) only. Via a logistic regression approach, we defined a subgroup with low risk for upgrade: women whose biopsies showed no individual cell necrosis, and either a) 1 focus of ADH with ≥50% removal, or b) 2-3 foci with ≥90% removal. Cases meeting these criteria had an upgrade rate of 4.9% (95% CI: 1.0-8.9%), compared to 21.4% (16.4-26.3%) in cases that did not meet this low-risk definition. CONCLUSIONS: ADH on core biopsy with low risk of upgrade to cancer is defined by lack of individual cell necrosis, number of foci of ADH, and percent of imaging lesion removed. If these findings are validated, women whose biopsies meet low-risk criteria might be considered for prevention therapy and surveillance without surgical excision.

Is axillary surgery beneficial for patients with adenoid cystic carcinoma of the breast?

BACKGROUND AND OBJECTIVES: Adenoid cystic carcinoma (ACC) is a rare, typically triple-negative, breast cancer reported to have a favorable prognosis and low rate of nodal metastasis. No consensus guidelines exist for axillary staging and treatment. METHODS: We identified all patients with ACC evaluated at our institution from January 1994 to August 2016. Patient, tumor, and treatment variables were abstracted and analyzed. RESULTS: We identified 20 pure ACCs (0.13% of all invasive breast cancers) with size range 0.2-4.8 cm, in 19 women, median age 59 years. Preoperative axillary ultrasound was normal in 10/13 women and suspicious in 3/13 who had a subsequent negative lymph node fine needle aspiration (FNA). Fifteen patients (75%) had sentinel lymph node surgery and were pathologically node-negative, while the remaining five had no axillary surgery. With 3.6 years median follow-up (range 0.2-38.6 years), three patients experienced an in-breast recurrence at 2, 16, and 17 years, respectively, while none recurred in regional nodes. CONCLUSIONS: We observed no cases of nodal metastasis in 20 consecutive cases of ACC of the breast. Preoperative axillary ultrasound with FNA of suspicious nodes accurately predicted pathologic nodal stage. These data suggest axillary surgery might be omitted safely in patients with pure ACC and a clinically negative axilla.

Does BMI affect the accuracy of preoperative axillary ultrasound in breast cancer patients?

INTRODUCTION: Obesity affects 36 % of American women and is a well-documented breast cancer risk factor. Preoperative axillary ultrasound (AUS) is used routinely for axillary staging in newly diagnosed breast cancer patients; However, the impact of obesity on the usefulness of AUS is unknown. Our aim was to evaluate the effect of body mass index (BMI) on the performance of AUS. METHODS: From our prospective breast surgery database, we identified 1,510 consecutive invasive breast cancers in patients undergoing primary surgery, including axillary operation, from January 2010 to July 2013. Preoperative AUS was performed in 1,375 cases (91 %). We analyzed patient, pathology and imaging data. RESULTS: Median BMI was 27.4 and 479 patients (36 %) were classified as obese (BMI ≥ 30). Most tumors were T1 (71 %) and estrogen receptor-positive (87 %). AUS was suspicious in 401 (29 %) patients, of whom 374 had ultrasound-guided lymph node fine-needle aspiration (FNA). Overall, 124 patients (33.2 %) were FNA positive. FNA identified disease preoperatively in 35.8 % of node-positive obese patients. For all BMI categories (normal, overweight, obese), AUS was predictive of pathologic nodal status (p < 0.0001). AUS sensitivity did not differ across BMI categories, while specificity and accuracy were better for overweight (p = 0.001 and 0.008, respectively) and obese (p = 0.007 and 0.02, respectively) patients, than for normal-BMI patients. CONCLUSIONS: Despite theoretical concern regarding both potential technical challenges and obesity-related lymph node alterations, the sensitivity of preoperative AUS for detecting nodal metastasis was similar in obese and non-obese patients, while specificity was better in obese patients. Preoperative AUS is valuable for preoperative nodal staging of obese breast cancer patients.

ERß1: characterization, prognosis, and evaluation of treatment strategies in ERα-positive and -negative breast cancer.

BACKGROUND: The role and clinical value of ERß1 expression is controversial and recent data demonstrates that many ERß antibodies are insensitive and/or non-specific. Therefore, we sought to comprehensively characterize ERß1 expression across all sub-types of breast cancer using a validated antibody and determine the roles of this receptor in mediating response to multiple forms of endocrine therapy both in the presence and absence of ERα expression. METHODS: Nuclear and cytoplasmic expression patterns of ERß1 were analyzed in three patient cohorts, including a retrospective analysis of a prospective adjuvant tamoxifen study and a triple negative breast cancer cohort. To investigate the utility of therapeutically targeting ERß1, we generated multiple ERß1 expressing cell model systems and determined their proliferative responses following anti-estrogenic or ERß-specific agonist exposure. RESULTS: Nuclear ERß1 was shown to be expressed across all major sub-types of breast cancer, including 25% of triple negative breast cancers and 33% of ER-positive tumors, and was associated with significantly improved outcomes in ERα-positive tamoxifen-treated patients. In agreement with these observations, ERß1 expression sensitized ERα-positive breast cancer cells to the anti-cancer effects of selective estrogen receptor modulators (SERMs). However, in the absence of ERα expression, ERß-specific agonists potently inhibited cell proliferation rates while anti-estrogenic therapies were ineffective. CONCLUSIONS: Using a validated antibody, we have confirmed that nuclear ERß1 expression is commonly present in breast cancer and is prognostic in tamoxifen-treated patients. Using multiple breast cancer cell lines, ERß appears to be a novel therapeutic target. However, the efficacy of SERMs and ERß-specific agonists differ as a function of ERα expression.

Facile Green Synthesis of Iron Oxide Nanoparticles and Their Impact on Cytotoxicity, Antioxidative Properties and Bactericidal Activity.

Background: Bioreductive processes are quite potent, effective and affordable for the synthesis of green nanoparticles (NPs), as compared to the physical and chemical methods. The present study aimed to evaluate the bactericidal, antioxidative and anticancer activity of turmeric rhizome-iron oxide nanoparticles (FeONPs) derived from the turmeric rhizome (Curcuma amada) using ferric chloride as a precursor. Methods: With focusing on the manufacture of FeONPs via green approach, we characterized the NPs using FTIR, FT-Vis, DLS, and UV-Vis spectroscopy. The produced particles were tested for antibacterial, antioxidant, and anticancer properties. The synthesized NPs were also examined using the MDA-MB-231 human epithelial breast cancer cell line and NCI-60 cancer cell lines. Results: The antioxidant activity of TR-FeONPs was concentration-dependent. The scavenging activity of TR-FeONPs was 76.09% at a concentration of 140 µg/ml. Using different concentrations of TR-FeONPs in the MTT assay against the MDA-MB-231 cell line indicated a reduction of less than 50% in cell viability at 125 µg/ml. Moreover, TR-FeONPs exhibited an effective bactericidal property. The gTR-FeONPs synthesized bioreductively were found to be effective in renal cancer, UO-31 cell line, with GI50 value of 66.64%. Conclusion: Our study showcases a sustainable method based on green chemistry principles to produce FeONPs utilizing turmeric rhizome. We anticipate that the FeONPs produced through this biosynthesis process could serve as a promising drug delivery system in cancer treatment and as an effective antimicrobial agent against various diseases.

Tongues Tied by Orofacial Myofunctional Therapy about Tongue Tie: A Narrative Review.

Aim and Background: The respective review articles aim is to provide an overview as well as describes and enlists different orofacial myofunctional therapy exercises as a modality for tongue tie secondary to surgery.Tongue tie is the basically a connection that joints base of tongue to the floor of mouth. This leads to difficulties various difficulties such as altered speech, oral habits, maligned teeth and many more. During formative years, most children successfully treated of tongue tie by releasing it, but problems start after its correction. That it may can reappear or may lead to same difficulties as prior. Parents and clinicians are only concerned about speech and aesthetics after release of tongue tie. But OMT plays important role ore and post-surgical procedure. OMT help in proper tongue posture along with reducing the probability of tissue reattachment after surgery by exercises. This therapy positively influenced functions by reducing deleterious habits. Methods: A review of relevant literature is predicated on articles found using free text terms, mesh terms, and some basic tongue tie as well as tongue tie release pamphlets that were published in English up until the year 2023 in the electronic databases PubMed, EBSCO, Scopus, Google Scholar, and Web of Science. With the aid of mesh keywords, the initial search yielded 38-40 articles; 20-35 were chosen depending on the requirements. Also we searched for orofacial myofunctional exercises or exercises recommended after tongue tie release. Results: Various exercises enlisted in our article that will guide a individual before and after tongue tie release which will give positive outcomes such as proper tongue posture, speech, swallow, regained aesthetics and self-esteem. Conclusion: Tongue plays an important role in development of perioral structures as well as in the swallow to good speech articulation and dental occlusion. So, as pediatric dentist its important know that after release of tongue tie what to do and how to maintain. This review article is focused on the various orofacial myofunctional therapy techniques employed for tongue tie but not a single one to describe them. Clinical significance: Our pertaining review act as a guide for clinicians as well as individuals to manage tongue tie after its release. How to cite this article: Shah SS, Agarwal PV, Rathi N, et al. Tongues Tied by Orofacial Myofunctional Therapy about Tongue Tie: A Narrative Review. Int J Clin Pediatr Dent 2024;17(1):109-113.

Amyloidosis of the breast: predominantly AL type and over half have concurrent breast hematologic disorders.

Amyloidosis is a disorder characterized by extracellular deposition of proteins in an abnormal fibrillar configuration. Amyloidosis can be localized or systemic and may affect any organ. Breast involvement by amyloidosis has rarely been reported. In this study, we described the characteristics of 40 cases of breast amyloidosis that were reviewed at the Division of Anatomic Pathology at Mayo Clinic from 1995 to 2011. The cohort included 39 women and 1 man with a mean age of 60 years. The type of amyloidosis, determined by immunohistochemistry or mass spectrometry-based proteomics in 26 patients, was immunoglobulin-associated in all cases (AL-kappa type in 15 (58%) cases, AL-lambda in 10 (38%) and mixed heavy and light chains (AH/AL) in 1 (4%) case). Mass spectrometry-based proteomics was able to determine the type of amyloidosis in 95% of cases tested compared with 69% of cases by immunohistochemistry. In addition to amyloidosis, the breast biopsy showed a hematologic disorder in 55% of cases, most commonly MALT lymphoma. One patient had concurrent intraductal carcinoma, but none had invasive carcinoma. Of the 15 patients seen in our institution, 53% had localized amyloidosis and 47% had extramammary amyloid involvement, which was diagnosed before breast amyloidosis in most patients. M-spike was detected in the blood in 62%. After a median follow-up of 33.5 months in 12 patients, 5 died, mostly of complications of lymphoma or leukemia. In conclusion, our findings indicate that breast amyloidosis is of the AL type in the vast majority of patients (usually kappa). It is associated with systemic amyloidosis in close to half of patients and with hematologic malignancy in the breast in over half of patients. Therefore, further work up to rule out hematologic malignancy and/or systemic amyloidosis is recommended. Mass spectrometry-based proteomics is superior to immunohistochemistry for typing of breast amyloidosis.

Imaging response and residual metastatic axillary lymph node disease after neoadjuvant chemotherapy for primary breast cancer.

BACKGROUND: Although surgical management of the breast after neoadjuvant chemotherapy (NAC) may be governed by treatment response, axillary management continues to be determined by stage at presentation. Axillary ultrasound (AUS) with fine-needle aspiration (FNA) is used to detect lymph node (LN) metastases for pre-NAC staging, but imaging assessment of treatment response in the axilla remains undefined. We evaluated post-NAC axillary imaging and surgical pathology to understand how imaging might direct axillary surgery. METHODS: We evaluated pre- and post-NAC axillary imaging and clinicopathologic data in 272 patients who received NAC for primary breast cancer and underwent operation at our institution from 2010 to 2012. Treatment response on imaging was categorized as complete (CR), partial (PR), and none/progression (NR). RESULTS: Pre-NAC axillary staging classified patients as AUS negative/no FNA (n = 61), FNA/LN negative (n = 42), and FNA/LN positive (n = 169). Post-NAC axillary imaging included AUS (n = 146), MRI (n = 139), and PET-CT (n = 38). At operation, 128 of 272 patients (47 %) were LN positive: 23.3 % (24 of 103) of cN0 and 61.5 % (104 of 169) of cN1-AUS/FNA-positive patients at presentation. Of the 65 cN1-ypN0 patients, 58.1 % (25 of 43) had an imaging CR by US, 58.6 % (17 of 29) by MRI, and 84.6 % (11 of 13) by PET-CT. The sensitivity of post-NAC axillary imaging in detecting persistent LN metastases for cN1-AUS/FNA-positive patients was 69.8 % for US, 61.0 % for MRI, and 63.2 % for PET-CT. CONCLUSIONS: Performance characteristics of AUS, MRI, and PET-CT, while informative, were inadequate to preclude surgical axillary staging of in breast cancer patients after NAC. Whether this information might be used to tailor surgical and postsurgical treatment requires further investigation.

Comparative Fluoride Ion Release Pre and Postrecharge Situations among Three Different Pediatric Dental Restorative Materials: An In Vitro Study.

Objectives: To determine the initial fluoride (F) release and rerelease after recharge of three pediatric dental restorative materials when aged in artificial saliva (M1) and deionized water (M2). Materials and methods: A total of 30 disks, 10 disks of each restorative material R1: Jen Rainbow, Jen Dent Ukraine; R2: Tetric® N-Flow, Ivoclar Vivadent, and R3: resin-modified glass ionomer cement (RMGIC) (Fuji II LC- GC Corporation) were fabricated and were tested for F dynamics in two different media, M1: artificial saliva, M2: deionized water group. The F initial release was measured on the 1st, 7th, 14th, 21st, and 30th day, and on the 31st day, acidulated phosphate F (APF) gel was applied and F rerelease was measured on the 31st, 37th, 44th, 51st, and 60th day using F ion-specific electrode (Orion). The result was statistically analyzed using two-way analysis of variance (ANOVA) and post hoc Bonferroni test. Results: Fluoride (F) ion release was significantly higher in deionized water than in artificial saliva (M1), and F ion rerelease (after recharge) was significantly higher in artificial saliva (M1). Fuji-II LC demonstrated a significantly (p < 0.05) higher F release and rerelease among all the tested materials. Among the tested composites, R2: Tetric® N-Flow exhibited significantly higher F dynamics than R1: Jen Rainbow composite. Conclusion: All the tested restorative materials exhibited optimum F release (0.024 ppm, that is, the range to prevent newer carious lesions) in both the pre and postrecharge conditions. Even though Fuji-II LC demonstrated significantly better F dynamics in the tested scenarios, Tetric® N-Flow has the additional advantage of improved mechanical retentive and esthetic properties along with the optimum F release in pre and postrecharge scenarios. How to cite this article: Mathias MR, Rathi N, Bendgude VD, et al. Comparative Fluoride Ion Release Pre and Postrecharge Situations among Three Different Pediatric Dental Restorative Materials: An In Vitro Study. Int J Clin Pediatr Dent 2022;15(6):729-735.

Orofacial Myofunctional Therapy in Tongue Thrust Habit: A Narrative Review.

AIM AND OBJECTIVE: The respective review article is to provide an overview of the various exercises in orofacial myofunctional therapy (OMT) as a treatment modality for tongue thrust habit. Tongue thrust is the persistence of an infantile swallow pattern during late childhood. This leads to breathing and speech difficulties, open bite, and protruded teeth. During formative years, most children successfully transition from an infantile to a mature swallowing pattern. However, a few develop a retained infantile swallow and tongue thrust habit which could be due to abnormal habit like thumb sucking or an underlying cause like enlarged adenoids. Adverse effects of these habits can be avoided by early detection and intervention in a growing child. Tongue thrust can be treated in different ways with early diagnosis, removal of underlying causes, correcting tongue posture, and breaking of habit with the use of orthodontic appliances. This review article is focused on the various OMT techniques employed for the correction of tongue thrust. There are several exercises in OMT which can help a child with tongue thrust. These can be performed at home under the supervision of the child's parents. Orofacial myofunctional therapy has provided a dramatic and positive influence on patients treated for tongue thrust. The joy of eating, speaking, and correct breathing can be regained along with confidence, self-esteem, and improved quality of life. Clinically, OMT plays a positive role by not only improving swallow but also the posture of tongue, improper muscle function, and reduces relapse of previous orthodontic treatments. HOW TO CITE THIS ARTICLE: Shah SS, Nankar MY, Bendgude VD, et al. Orofacial Myofunctional Therapy in Tongue Thrust Habit: A Narrative Review. Int J Clin Pediatr Dent 2021;14(2):298-303.

Pure tubular carcinoma and axillary nodal metastases.

BACKGROUND: Pure tubular carcinoma of the breast is a rare subtype with a low incidence of axillary lymph node metastases. The aim of this study was to determine the frequency of axillary lymph node metastasis in patients with pure tubular carcinoma. METHODS: We identified patients diagnosed with tubular carcinoma from 1987 to 2009 from our institution's tumor registry. Pathology slides were reviewed, and pure tubular carcinoma was defined as ≥ 90% tubule formation, low nuclear grade, and rare to no mitoses. Medical records were reviewed for clinicopathologic data including tumor size, number of positive and negative axillary lymph nodes, treatment, and recurrence. RESULTS: We identified 105 cases of pure tubular carcinoma of the breast in 103 patients. Median tumor size was 0.8 (range 0.1-1.8) cm. Nodal staging was performed in 93 cases (89%). Five patients (5.4%) had positive lymph nodes, and two patients (2.2%) had isolated tumor cells. All patients with lymph node metastases had tumors >0.8 cm in size. At 5.2 years' follow-up, no patients have developed recurrence or metastases, or have died from breast cancer. CONCLUSIONS: Axillary lymph node metastases are not common in small pure tubular carcinomas. Nodal staging may be omitted in small pure tubular carcinomas.

FNA of misclassified primary malignant neoplasms of the thyroid: Impact on clinical management.

BACKGROUND: Fine needle aspiration (FNA) cytology is a popular, reliable and cost effective technique for the diagnosis of thyroid lesions. The aim of our study was to review cases of misclassified primary malignant neoplasms of the thyroid by FNA, and assess the causes of cytologic misdiagnosis and their impact on clinical management. METHODS: Clinical data, FNA smears and follow-up surgical specimens of cases diagnosed with primary thyroid carcinoma were reviewed. RESULTS: Of the 365 cases with a malignant diagnosis by FNA over a period of 11 years, nine (2.4 %) were identified with discrepant histologic diagnosis with regard to the type of primary thyroid malignancy. In addition, four cases were added from the consultation files of the Massachusetts General Hospital. Areas of difficulty contributing to misclassification included overlapping cytologic features (n = 6), rarity of tumors (n = 3), and sampling limitations (n = 4). Of the 13 cases, 12 underwent total or near total thyroidectomy and one patient had concurrent surgical biopsy. Measurement of serum calcitonin levels in one case, with an initial cytologic diagnosis of medullary carcinoma, prevented unnecessary lymph node dissection. Misclassification of medullary carcinoma as papillary carcinoma precluded lymph node dissection in one case. Further management decisions were based on the final histologic diagnosis and did not require additional surgery. Two cases of undifferentiated (anaplastic) thyroid carcinoma were misdiagnosed as papillary thyroid carcinoma. Both patients received total thyroidectomies, which may not otherwise have been performed. CONCLUSIONS: A small subset of primary malignant neoplasms of the thyroid may be misclassified with regard to the type of malignancy on FNA. The majority of primary malignant neoplasms diagnosed on FNA require thyroidectomy. However, initial cytologic misclassification of medullary carcinoma or undifferentiated carcinoma as other malignant neoplasms or vice versa may have an impact on clinical management.

Albumin In Situ Hybridization Can Be Positive in Adenocarcinomas and Other Tumors From Diverse Sites.

OBJECTIVES: Albumin messenger RNA (mRNA) expression is a marker of hepatocellular differentiation. Most published data are from review of tissue microarrays, and albumin in situ hybridization (ISH) expression across several tumor types is incompletely characterized. METHODS: Sections from 221 tumors were evaluated for albumin mRNA. Immunohistochemistry was used to confirm diagnoses. Albumin ISH was performed according to manufacturer-provided instructions. Fifty-nine cases were evaluated with both commercial ISH assays. RESULTS: Albumin mRNA was detected in all hepatocellular carcinomas (HCCs) and 81% of intrahepatic cholangiocarcinomas. Lung (20%), gallbladder (39%), hepatoid pancreatic (n = 1 of 1) adenocarcinoma, breast invasive ductal carcinoma (18%), yolk sac tumor (25%), and acinar cell carcinoma (29%) showed expression. Both assays were concordant in 93% of cases. CONCLUSIONS: Albumin ISH was expressed in all HCCs studied. It was also positive in intrahepatic cholangiocarcinoma and patchy positive in gallbladder adenocarcinoma and a subset of other neoplasms, which can be a potential pitfall.

Endometrial eosinophilic syncytial change related to breakdown: immunohistochemical evidence suggests a regressive process.

Eosinophilic syncytial change (ESC), also known as papillary syncytial change, occurs in association with endometrial breakdown and bleeding, especially in nonphysiological conditions. When prominent, this morphological alteration yields a pattern of eosinophilic epithelial cells, often in pseudopapillary arrangements that can mimic cellular changes seen in metaplastic and atypical endometrium. To determine if ESC represents a proliferative, regenerative process or a degenerative, retrogressive alteration, we assessed whether the cells of ESC were actively growing. Our methodology involved a retrospective immunohistochemical study on endometrial biopsies with proliferation markers Ki-67 (MIB-1 antibody) and phosphohistone H3 Ser 28 (pHH3) in 15 cases of multifocal ESC associated with benign endometrium, 5 cases of atypical hyperplasia, and 7 cases of endometrial carcinoma. The Ki-67 proliferative index and the pHH3 mitotic index were calculated per 100 cells for each case. On immunohistochemical analysis, the Ki-67 labeling index was 1.3% for cases of ESC (mean age, 53 yr), 15.8% in atypical hyperplasia (mean age, 51.6 yr), and 42.6% in endometrial carcinoma (mean age, 68.1 yr). In the endometrial cancers, the Ki-67 proliferative index was 10.6% for FIGO grade 1 tumors (n=3), 27.6% for grade 2 tumor (n=1), and 79.6% for serous carcinoma (n=3). The mitotic index calculated from pHH3 immunostaining was zero in all cases of ESC, whereas it was 2.3% in atypical hyperplasia and 4.8% in endometrial carcinomas (2.4% for grade 1, 3% for grade 2, and 7.8% for serous). Our results indicate that ESC is a regressive change. Furthermore, when there is a question of whether eosinophilic endometrial epithelium represents this change, a combination of Ki-67 and pHH3 immunostains can be helpful in distinguishing this entity from more significant processes including carcinoma.

Adenocarcinoma in situ arising in vulvar papillary hidradenoma: report of 2 cases.

Adenocarcinoma in situ rarely occurs in vulvar papillary hidradenoma. We encountered 2 cases of adenocarcinoma in situ arising in a papillary hidradenoma of the vulva. Both patients were asymptomatic women, aged 83 and 92 years, who presented with nodules (1.0 and 2.0 cm) on the vulva. Macroscopically, the lesions seemed tan-pink, fleshy, and well circumscribed. One tumor ulcerated the overlying epidermis. On microscopic examination, the tumors showed focal features of benign hidradenoma at the periphery with transitions into areas of increasing cytologic atypia that fulfilled criteria for adenocarcinoma in situ similar to that seen in the breast. One tumor showed a predominant cribriform pattern with moderate atypia and many mitoses; the other showed a mixture of cribriform and micropapillary patterns, mild atypia, and fewer mitotic figures. There was no evidence of destructive invasion or desmoplasia in either tumor. Both lesions show areas strongly immunoreactive for mammaglobin and gross cystic disease fluid protein 15 as well as estrogen and progesterone receptor protein in 1 case. There was no evidence of benign ectopic breast tissue within or adjacent to the neoplasms. Both patients underwent local excision with no evidence of tumor recurrence at 15 and 32 months of follow-up. The fact that these tumors displayed morphologic and immunohistochemical features that resembled ductal carcinoma in situ of the breast demonstrates the close homology between papillary hidradenoma and breast epithelium. In the absence of invasion, our experience suggests that these tumors can be cured by local excision.

Hepatocyte Antigen Expression in Barrett Esophagus and Associated Neoplasia.

Hepatocyte antigen or hepatocyte paraffin 1 (Hep Par 1) is widely used as a diagnostic immunomarker for hepatocellular carcinoma. It has also been identified as a rate-limiting enzyme of the urea cycle, carbamoyl phosphate synthetase 1. Hep Par 1 has been detected in non-neoplastic small intestinal epithelium, but its expression in Barrett esophagus and its related neoplasia has not been well investigated. We immunohistochemically evaluated expression of Hep Par 1 on 75 cases of Barrett esophagus (25 cases without dysplasia, 16 cases with low-grade dysplasia, 25 cases with high-grade dysplasia, and 9 cases with intramucosal adenocarcinoma) on endoscopic biopsies and endoscopic mucosal resections. All 25 cases without dysplasia (100%) showed granular cytoplasmic Hep Par 1 staining (24 diffuse and 1 focal). Of the 16 cases with low-grade dysplasia, 12 (75%) were positive (5 diffuse and 7 focal), whereas 4 (25%) were negative (P=0.018). Of the 25 cases with high-grade dysplasia, 9 (36%) showed focal positivity, whereas 16 (64%) were negative (P=0.0001). Similarly of the 9 cases of intramucosal adenocarcinomas 3 (33%) were focally positive, whereas 6 (67%) were negative (P=0.0001). Hep Par 1 is diffusely expressed in non-neoplastic Barrett esophagus while it is frequently lost in related dysplasia and adenocarcinoma, suggesting decreased level of HepPar1 may represent an early event in Barrett-related tumor genesis. This warrants additional investigation to look for the possible role of carbamoyl phosphate synthetase 1 in the pathogenesis of Barrett-related neoplasia.