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.

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.

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.

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.

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.

Granulomatous diseases of the breast and axilla: radiological findings with pathological correlation.

OBJECTIVES: This article reviews our experience and describes the literature findings of granulomatous diseases of the breast and axilla. METHODS: After approval of the Institutional Review Board was obtained, the surgical pathological records from January 2000 to January 2017 were searched for the keyword granulomatous. Clinical, imaging and histology findings were reviewed by both a fellowship-trained radiologist and a breast-imaging consultant radiologist, reviewing 127 patients (age range, 32-86 years; 126 women and 1 man). RESULTS: Most common causes of granulomatous lesions of the breast and axilla included silicone granulomas 33% (n = 42), fat necrosis 29% (n = 37) and suture granulomas 11% (n = 14). In 16% (n = 20), no cause could be found and clinical history was consistent with idiopathic granulomatous mastitis. Other granulomatous aetiologies included granulomatous infections, sarcoidosis and Sjögren's syndrome. Causes of axillary granulomatous disease were similar to the breast; however, a case of cat-scratch disease was found that only involved the axillary lymph nodes. They can have a variable appearance on imaging and may mimic malignancy with irregular masses seen on mammography, ultrasound and magnetic resonance imaging. Fistulas to the skin and nipple retraction can suggest chronicity and a granulomatous aetiology. Combination of clinical history, laboratory and imaging findings can be diagnostic. CONCLUSIONS: Granulomatous processes of the breast are rare. The diagnosis can, however, be made if there is relevant history (prior trauma, silicone breast implants, lactation), laboratory (systemic or infectious processes) and imaging findings (fistula, nipple retraction). Recognising these entities is important for establishing pathological concordance after biopsy and for preventing unnecessary treatment. TEACHING POINTS: Breast granulomatous are rare but can mimic breast carcinoma on imaging Imaging with clinical and laboratory findings can correctly diagnosis specific granulomatous breast diseases Recognition of the imaging findings allows appropriate pathological concordance and treatment.

Treponema pallidum Immunohistochemistry is positive in human intestinal Spirochetosis.

BACKGROUND: Human intestinal spirochetosis (IS) has been recognized for decades, but whether it represents commensalism or a pathogenic process remains controversial. IS is diagnosed on routine stains with confirmation by silver stains but these stains are labor intensive and slow to read. We evaluated the Treponema pallidum immunostain as a diagnostic adjunct for IS. METHODS: We retrieved biopsies from 33 patients with IS for this study. Each case was tested by Warthin-Starry (WS) and T. pallidum immunohistochemistry (IHC). Species specific genotyping was performed in 3 cases. RESULTS: Patients with IS ranged from 22 to 82 years without gender predilection. IS involved normal (n = 15), and inflamed (n = 5) mucosa and colonic polyps (n = 13). Warthin-Starry and T. pallidum IHC were positive in all cases including both species of Brachyspira. Six (18%) symptomatic patients were treated for IS, and experienced resolution. In patients diagnosed with incidental IS on cancer screening (n = 5), follow up biopsies, without therapy, were negative for IS. T. pallidum IHC required 75 min less hands-on time than WS for performance and was faster to interpret. CONCLUSIONS: T. pallidum IHC can be used to confirm the diagnosis of IS and is easier to perform and faster to interpret than WS.

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.

Copper deposition in focal nodular hyperplasia and inflammatory hepatocellular adenoma.

AIMS: To examine copper deposition in focal nodular hyperplasia (FNH) and inflammatory hepatocellular adenoma (IHA) and to determine if it can play a role in their differentiation. METHODS: 28 FNHs and 19 IHAs from surgical resections showing typical morphological and immunohistochemical features were stained with rhodanine to evaluate for copper deposition. Histological features such as nodularity, fibrous bands, ductular proliferation, steatosis, ballooned hepatocytes and lymphocytic inflammation were also scored. RESULTS: Copper deposition was detected in 96% (27/28) of FNHs and 37% (7/19) of IHAs, P<0.001. In all cases, copper was seen within the hepatocytes only around the pseudo-portal tracts or areas of fibrosis. Copper deposition in IHA was significantly associated with presence of lymphocytic inflammation (P=0.04) but not associated with features like nodularity, fibrous bands, ductular proliferation, ballooned hepatocytes and steatosis (P>0.05, for all). In FNH, the presence and degree of copper deposition was not significantly associated with any histological features (P>0.05, for all). CONCLUSIONS: Copper deposition occurs more frequently in FNH (96%) than IHA (37%), P<0.001. However, the presence of copper alone cannot be used as a feature to differentiate between FNH and IHA.

A subset of well-differentiated hepatocellular carcinomas are Arginase-1 negative.

Hepatocellular carcinoma (HCC) is a common malignancy both in the United States of America and worldwide. Despite the refinement of imaging techniques in at-risk populations, a needle biopsy diagnosis remains an important diagnostic tool for HCC in many cases. Various immunohistochemical markers have been developed to facilitate this diagnosis, such as HepPar-1, glypican-3 and, most recently, arginase-1. Amongst them, arginase-1 has been shown to have superior sensitivity and specificity than the others. Performance of arginase-1 has been reported to be excellent for diagnosis of well-differentiated HCCs, with some tail-off in sensitivity for poorly differentiated tumors. Our experience has suggested that a subset of well-differentiated HCCs can be negative for arginase-1. We examined 68 consecutive confirmed cases of well-differentiated HCC diagnosed on needle biopsy, and found 7 (10%) to be completely negative for arginase-1. This finding is of fundamental clinical importance in view of previous studies that have shown arginase-1 to be always positive in well-differentiated HCC.

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.

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.

Aberrant CDX2 expression in hepatocellular carcinomas: an important diagnostic pitfall.

CDX2 is a sensitive and specific marker of intestinal differentiation. It is routinely used in surgical pathology, as its expression within a tumor favors an origin within the gastrointestinal tract. We had anecdotally encountered occasional hepatocellular carcinomas (HCCs) that were CDX2 positive. CDX2 expression in HCC has not yet been reported, but it has also not been examined in detail. Therefore, we evaluated CDX2 expression in a large number of resected HCCs. Full tumor sections from 172 resected HCCs and 6 resected fibrolamellar carcinomas (FLCs) were stained for CDX2. Nine (5.2%) of 172 HCCs were positive for CDX2, whereas all 6 FLCs were negative. CDX2 expression in HCCs was more commonly seen in poorly differentiated tumors (5 of 16 cases, 31%) than well and moderately differentiated tumors (4 of 156 cases, 2.5%), P = .0004. No other statistically significant correlations were observed (P>.05). Results of our study show that a small subset (5%) of HCCs can be CDX2 positive. Awareness of this phenomenon is important because CDX2 expression in a liver tumor does not completely exclude a diagnosis of HCC.

Idiopathic granulomatous mastitis: imaging update and review.

OBJECTIVES: The purpose of this study was to review the imaging features of idiopathic granulomatous mastitis (IGM) with clinical and pathology correlation. METHODS: With institutional review board (IRB) approval, a retrospective search of the surgical pathology database from January 2000 to July 2015 was performed. Clinical, imaging and histology findings were reviewed. Cases of granulomatous mastitis without a known source, diagnosed with percutaneous or surgical biopsy, were included in our analysis. RESULTS: Seventeen cases of IGM were identified with imaging available for review. The majority of patients presented with a palpable abnormality, whereas a minority were asymptomatic with an abnormal screening mammogram. At imaging, IGM most often demonstrated a focal asymmetry at mammography, a hypoechoic mass with irregular or angular margins at ultrasound, and robust enhancement with mixed progressive and plateau kinetics at magnetic resonance imaging (MRI). Axillary lymph nodes were reactive in appearance at ultrasound. Molecular breast imaging performed in one case showed mild focal asymmetric radiotracer uptake. CONCLUSION: IGM is a rapidly progressive rare inflammatory condition of the breast resulting in non-necrotizing granuloma formation. Imaging features mimic breast carcinoma and diagnosis can be difficult. Radiologists' awareness of this condition is essential to prevent delayed or unnecessary treatment. TEACHING POINTS: • Idiopathic granulomatous mastitis is rapidly progressive inflammatory condition. • Imaging features may mimic breast carcinoma or infection. • Ultrasound shows irregular hypoechoic masses with increased vascularity and sinus tracts. • MRI shows irregular, enhancing masses or non-mass enhancement with microabscesses. • MRI is useful for assessment of breast involvement and response to treatment.

Arginase-1 is frequently positive in hepatoid adenocarcinomas.

Hepatoid adenocarcinoma is a rare extrahepatic tumor, which shows morphological and immunohistochemical similarities to hepatocellular carcinoma (HCC). Hence, hepatoid adenocarcinoma can cause diagnostic confusion with HCC. Arginase-1 immunostain has been recently shown to be an excellent marker of normal hepatocytes and is a sensitive and specific marker for HCC. However, the expression of Arginase-1 in hepatoid adenocarcinoma has not been evaluated in detail. Eight cases of hepatoid adenocarcinoma were immunostained with Arginase-1, Hepar-1, Glypican-3, CK7, CK20, CK19, polyclonal carcinoembryonic antigen, ɑ-fetoprotein, CDX2, and TTF-1. Albumin in situ hybridization was performed in 4 cases. All 8 cases were positive for Hepar-1. Arginase-1 was positive in 5 (62.5%) of 8 cases; 2 of these cases showed diffuse staining, while 3 showed patchy staining. Glypican-3, CK7 and ɑ-fetoprotein were each positive in 4 (50%) of 8 cases. CK19 was positive in 3 (37.5%) of 8 cases. polyclonal carcinoembryonic antigen showed canalicular staining in 3 (37.5%) of 8 cases and albumin in situ hybridization was positive in 3 (75%) of 4 cases. CDX2 was positive in 2 (25%) of 8 cases, both arising from the stomach. CK20 was positive in 1 (12.5%) of 8 case while TTF-1 was negative in all cases. Hepatoid adenocarcinoma has a similar immunostaining profile as HCC. Arginase-1 expression is common (62.5%) in hepatoid adenocarcinoma and hence it is not useful in distinguishing HCC from hepatoid adenocarcinoma.

Immunostains Used to Subtype Hepatic Adenomas Do Not Distinguish Hepatic Adenomas From Hepatocellular Carcinomas.

Immunostains are used to subtype hepatic adenomas to stratify for the risk of malignant transformation. The most common panel of immunostains used for this purpose includes liver fatty acid-binding protein (LFABP), serum amyloid A (SAA) protein, C-reactive protein (CRP), and glutamine synthetase (GS). Importantly, some pathologists use these stains in an attempt to distinguish hepatocellular carcinomas (HCC) from hepatic adenomas. However, there are limited data on the performance of these stains in HCCs. To investigate the staining characteristics of HCCs, we studied 159 HCCs (92 well-differentiated, 67 moderately differentiated, and 7 poorly differentiated) and 7 fibrolamellar carcinomas for the expression of LFABP, SAA, CRP, and GS. All of the stains were positive in at least a subset of HCCs: SAA was positive in 27 of 159 (17%), CRP in 86 of 159 (54%), and GS in 23 of 47 (49%) cases; LFABP showed loss of staining in 36 of 159 (23%) cases. Fibrolamellar carcinomas were consistently CRP positive (7 of 7 cases) and frequently showed loss of LFABP (4 of 7 cases). There was no association between expression of SAA, CRP, and GS as well as loss of LFABP expression and other clinicopathologic features. HCCs with loss of LFABP were more frequently associated with negative GS expression (11 of 14 cases, P=0.02). These data show that immunostains used to subtype hepatic adenomas are not useful for distinguishing HCCs from hepatic adenomas and should be used only after a diagnosis of hepatic adenoma has been made using other criteria.