The yield and impact of pulmonologist-performed EUS-B-FNA of subdiaphragmatic lesions-an institutional experience.

INTRODUCTION: Pulmonologists can biopsy structures below the diaphragm using the convex curvilinear ultrasound bronchoscope via the esophagus (EUS-B). The literature with respect to the value of EUS-B, rapid on-site evaluation, and final diagnostic yield for structures below the diaphragm is limited. We review our institutional experience. MATERIALS AND METHODS: Our database was queried retrospectively for EUS-B fine needle aspirations (FNAs) from 2013 to 2021. All procedures involving EUS-B-FNA of subdiaphragmatic structures were selected for analysis. The following data elements were collected for each patient: age, gender, clinical indication, sample site, on-site adequacy (OSA), preliminary and final diagnoses, and sufficiency of cell block for ancillary studies. RESULTS: A total of 75 subdiaphragmatic sites were biopsied in 74 patients. Of which, 87% of samples subjected to rapid on-site evaluation were deemed to contain adequate material (OSA+). There were no false-positive OSAs. Six cases remained nondiagnostic at the final diagnosis. The final diagnostic yield (with cell block) was 92% (69/75 cases). Cell block was sufficient for immunohistochemistry or special stains in all applicable cases (n = 36). Molecular testing was requested for 11 cases and successful in 10 (91%). Sampling of subdiaphragmatic sites changed the stage in 67% (38/57) of lung cancer patients. CONCLUSIONS: Pulmonologists can perform EUS-B-FNA of subdiaphragmatic sites with high OSA and final diagnostic yield when assisted by cytopathologists. Strong correlations exist between OSA, cell block adequacy, and subsequent capacity to perform ancillary testing. EUS-B below the diaphragm can make an important contribution to the diagnosis of lung cancer, nonpulmonary malignancies, and other diseases.

Prophylactic Risk-reducing Hysterectomies and Bilateral Salpingo-oophorectomies in Patients With Lynch Syndrome: A Clinicopathologic Study of 29 Cases and Review of the Literature.

Lynch syndrome (LS) is associated with an increased risk for colorectal, endometrial, and ovarian carcinomas in women. Risk-reducing hysterectomy and bilateral salpingo-oophorectomy (RRHSO) has been shown to be a cost-effective form of management and prevention of gynecological malignancies in patients with LS. Studies of incidental gynecologic malignancies identified in RRHSO are limited. In addition, recommendations on optimal handling of this type of specimen have ranged from submitting for microscopic examination the entire endometrium, fallopian tubes and ovaries to submitting only routine representative sections of these organs. In this study, we present the clinicopathologic findings of 29 cases of LS patients that underwent risk-reducing gynecologic surgery at our institution over a period of 13 yr. Clinical-pathologic information was obtained from the patients' charts and pathology reports. Significant pathologic abnormalities were identified in 17% (5/29) of cases, all showing endometrial hyperplasia. Four of them with atypical and 1 without atypical. All of our cases with endometrial pathology had significant findings on preoperative endometrial sampling. To further study the recommendation of in toto submission of the endometrium, ovaries and fallopian tubes and the utility of preoperative endometrial sampling, we undertook a literature review of all the reported cases of incidental pathologic findings identified in RRHSO. The findings of our cohort and the literature reviewed support in toto submission of endometrium, and adnexal structures in the absence of gross lesions. In addition, our findings show a definite benefit for preoperative endometrial sampling as part of the workup for LS patients undergoing RRHSO.

The Impact of Partial Weak Staining in Normal Breast Epithelium on the Reliability of Immunohistochemistry Results in HercepTest-positive Breast Cancer.

INTRODUCTION: Although normal epithelial cells do not show human epidermal growth factor receptor-2 (HER2) gene amplification and should lack membrane staining by HER2 immunohistochemistry (IHC), HER2 staining in benign breast epithelium is occasionally encountered. The significance of this occurrence has not yet been adequately studied, and its associated American Society of Clinical Oncology/College of American Pathologists recommendations are vague. Our objective is to assess the correlation between HER2 IHC 3+ breast cancer cases with normal epithelium staining (NES) and their corresponding fluorescence in situ hybridization (FISH) results, and to suggest recommendations for interpretation. MATERIALS AND METHODS: A total of 154 breast cancer cases with HER2 IHC 3+ were reviewed. NES, along with other clinicopathologic characteristics, were recorded. NES was scored as present or absent. All study cases were sent for FISH testing. All cases, and particularly those that showed false positivity for IHC (positive IHC, negative FISH) were examined for NES. RESULTS: Of the 154 cases, 146 cases were FISH-positive (94.8%) and 2 failed FISH testing (1.3%). Conversely, 22% (34/154) of the cases showed NES for HER2. Of these 34 cases, 23 (67%) were FISH-amplified, 9 (26%) were FISH not amplified, and 2 failed FISH testing. Notably, all of the false-positive (FISH-negative) breast cancer cases showed some degree of positivity in normal breast epithelium. CONCLUSIONS: Our findings, though descriptive, show a very strong association between NES and false-positive HER2 IHC. This confirms the need to carefully evaluate IHC-positive breast cancers for NES, and to have a low threshold for confirmatory testing by FISH.

Angiotropism in recurrent cutaneous squamous cell carcinoma: Implications for regional tumor recurrence and extravascular migratory spread.

Extravascular migratory metastasis is a form of cancer metastasis in which tumor cells spread by tracking along the abluminal aspect of vessel walls without breaking the vascular endothelial lining or intraluminal invasion. This phenomenon has been extensively described in melanoma and is being increasingly recognized in other neoplasms. Various modalities of treatment, including radiation-, chemo-, targeted-, and immune- therapies may potentially induce angiotropic behavior in neoplastic cells. Although there is a risk for tumor recurrence and metastasis, angiotropism may be under-recognized and is rarely reported. Here, we report a case of recurrent poorly-differentiated acantholytic squamous cell carcinoma of the scalp with extensive perineural invasion, previously treated with multiple therapies. There was multifocal extravascular cuffing of neoplastic cells around and focally involving the walls of small to medium-caliber blood vessels within and surrounding the tumor, without obvious tumor intravasation. In addition, small subtle nests of neoplastic keratinocytes were noted along the abluminal aspect of a large-caliber deep dermal blood vessel in an en-face margin, away from the main tumor mass. Such involvement can be difficult to identify; and thus, may be missed particularly during intra-operative frozen section evaluation, leading to false-negative margins and is therefore, a diagnostic pitfall.

CDH1 Gene and Hereditary Diffuse Gastric Cancer Syndrome: Molecular and Histological Alterations and Implications for Diagnosis And Treatment.

Gastric cancer, a group of common malignancies, results in the most cancer mortality worldwide after only lung and colorectal cancer. Although familial gastric cancers have long been recognized, it was not until recently that they were discovered to be associated with mutations of specific genes. Mutations of CDH1, the gene encoding E-cadherin, are the most common germline mutations detected in gastric cancer and underlie hereditary diffuse gastric cancer (HDGC) syndrome. All reported HDGCs are the pure diffuse type by Lauren classification and are associated with dismal prognosis once the tumor invades the submucosa. Because CDH1 germline mutations are inherited in an autosomal-dominant fashion and have high penetrance, the International Gastric Cancer Linkage Consortium (IGCLC) developed criteria to facilitate the screening of CDH1 mutation carriers; these criteria have been proven to have excellent sensitivity and specificity. Recent histologic studies suggest that HDGC progresses through several stages. Even when the tumor becomes "invasive" in lamina propria, it may stay indolent for a long time. However, the molecular mechanisms that induce the transitions between stages and determine the length of the indolent phase remain to be determined. Although the standard management for CDH1 mutation carriers is prophylactic total gastrectomy, many questions must be answered before the surgery can be done. These include the optimal surveillance strategy, the best strategy to choose surgical candidates, and the ideal time to perform surgery. In addition to increasing the risk of gastric cancer, CDH1 germline mutations also increase the risk of invasive lobular carcinoma of the breast, and possibly colorectal adenocarcinoma, and are associated with blepharocheilodontic syndrome (a congenital development disorder). However, the optimal management of these conditions is less established owing to insufficient data regarding the risk of cancer development. This review focuses on molecular and histological findings in HDGC, as opposed to sporadic diffuse gastric cancer, and their implications for the management of CDH1 mutation carriers and the diagnosis and treatment of HDGC. Other conditions associated with CDH1 germline mutations and future research directions are also discussed.

Cholangiocarcinoma Presenting as Linitis Plastica with Unusual Metastases to the Psoas Muscle and Urinary Bladder.

Cholangiocarcinoma offers poor prognosis. Infrequent sites of metastasis are poorly described and often diagnostically delayed or missed. Bile duct brush cytologies provide poor diagnostic sensitivity/specificity. We present an unusual case of cholangiocarcinoma in a 34-year-old woman with rare distant metastasis to the psoas muscle and urinary bladder. It is the first case of metastatic cholangiocarcinoma presenting as linitis plastica, and our patient is the youngest to be described with metastatic cholangiocarcinoma to the psoas muscle leading to diagnosis. We conclude that seemingly idiopathic biliary strictures that fail to respond to testing should prompt alarm and referral for cholangioscopy, where available.

Changing frequency of equivocal HER-2/neu scores and factors predictive of negative HER 2/neu fluorescent in situ hybridisation in invasive carcinomas of the breast.

BACKGROUND: Analysis of human epidermal growth factor receptor 2 (HER-2) status has become standard of care in breast cancer patients due to its important prognostic and therapeutic implications. Immunohistochemistry (IHC) is the most commonly used primary method for detection of HER-2 overexpression. Controversy exists on the interpretation of samples that are equivocal for HER 2 status (IHC 2+). Recent guidelines state that samples equivocal for HER 2 status require validation with fluorescent in situ hybridisation (FISH). The use of FISH, however, despite higher accuracy comes at a higher cost that is not affordable to all patients. METHODS: This study is a retrospective study conducted at the American University of Beirut Medical Center, including women diagnosed with breast cancer with equivocal IHC scores presenting between 2009 and 2011. We attempted to correlate clinicopathological characteristics of patients diagnosed with breast cancer that can influence conclusions made on HER 2 status when analysing IHC equivocal samples in an effort to decrease the need for FISH testing. 113 patients in our records were included; charts were reviewed for different patient clinical characteristics and samples were analysed for pathological characteristics. RESULTS: Using logistic regression, progesterone receptor status and HER-2 staining of the normal glands around the tumour by IHC were the two statistically significant variables that showed association with FISH results. The strength of progesterone receptor status positivity and HER-2 staining of the normal glands around the tumour were proportional to the likelihood of a negative FISH. Also, the presence of strong and diffuse hormone receptor positivity in low-grade tumours was predictive of negative HER-2 status. CONCLUSIONS: In countries where resources are strained, oncologists need to think of measures to minimise the increasing financial burden of cancer care. Our study serves to highlight a few clinicopathological characteristics that might eliminate the need for further testing through FISH.

Follicular dendritic cell sarcoma of the head and neck expressing thyroid transcription factor-1: a case report with clinicopathologic and immunohistochemical literature review.

Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm of follicular dendritic cells, most commonly affecting the lymph nodes and extranodal soft tissues of the head and neck, but also potentially arising in any visceral organ. FDCS with its diverse morphologies raises an occasionally challenging differential of primary and metastatic tumors with overlapping histologic and immunohistochemical features. When involving the head and neck, FDCS may be confused with squamous cell carcinoma, undifferentiated carcinoma, extracranial meningioma, and variants of papillary thyroid carcinoma. We describe here a case of FDCS showing nuclear grooves, intranuclear pseudoinclusions, diffuse epithelial membrane antigen and focal cytokeratin staining, and the first documented report of positivity for thyroid transcription factor-1. A discussion of the differential diagnosis and potential diagnostic pitfalls in FDCS brought forth by thyroid transcription factor-1 immunoreactivity and a full review of clinicopathologic and immunohistochemical features of head and neck FDCS are presented.

Chondro-osseous respiratory epithelial adenomatoid hamartoma of the nasal cavity

INTRODUCTION: Chondro-osseous respiratory epithelial adenomatoid hamartoma (COREAH) is a benign lesion of the nose and sinuses that is extremely rare, with only 2 cases reported in the literature to date. CASE REPORT: We present herein the third reported case of COREAH, in a 38-year-old woman who presented with left nasal obstruction and a mass in her left nasal cavity. The mass was completely resected endoscopically. Microscopic examination showed hamartomatous proliferation of respiratory-type glands with mucinous metaplasia admixed with numerous spicules of mature bone, characteristic of COREAH. CONCLUSION: COREAH is a benign hamartomatous proliferation of respiratory epithelium, submucosal glands, and chondro-osseous mesenchyme. The clinical differential diagnoses for such lesions include glandular hamartoma, inflammatory polyp, inverted papilloma, and low-grade sinonasal adenocarcinoma. Recognition of this lesion as benign despite its potentially worrisome radiographic appearance is important to avoid an unnecessarily radical surgical procedure.

Chondro-osseous respiratory epithelial adenomatoid hamartoma of the nasal cavity.

INTRODUCTION: Chondro-osseous respiratory epithelial adenomatoid hamartoma (COREAH) is a benign lesion of the nose and sinuses that is extremely rare, with only 2 cases reported in the literature to date. CASE REPORT: We present herein the third reported case of COREAH, in a 38-year-old woman who presented with left nasal obstruction and a mass in her left nasal cavity. The mass was completely resected endoscopically. Microscopic examination showed hamartomatous proliferation of respiratory-type glands with mucinous metaplasia admixed with numerous spicules of mature bone, characteristic of COREAH. CONCLUSION: COREAH is a benign hamartomatous proliferation of respiratory epithelium, submucosal glands, and chondro-osseous mesenchyme. The clinical differential diagnoses for such lesions include glandular hamartoma, inflammatory polyp, inverted papilloma, and low-grade sinonasal adenocarcinoma. Recognition of this lesion as benign despite its potentially worrisome radiographic appearance is important to avoid an unnecessarily radical surgical procedure.

Clinicopathologic characteristics of carcinomas that develop after a biopsy containing columnar cell lesions: evidence against a precursor role.

BACKGROUND: Columnar cell lesions are frequently associated with atypical ductal hyperplasia, lobular neoplasia, and tubular carcinoma, and have been suggested as a precursor lesion for low-grade carcinomas. However, in long-term follow-up studies, columnar cell lesions are associated with only a slight increase in later breast cancer development. If columnar cell lesions are precursor lesions, one would expect subsequent cancers to develop at the same site as the biopsy and to be preferentially of low grade. The goal of this article is to review the clinical and pathologic features of carcinomas that develop after a diagnosis of columnar cell lesion to try to establish whether these lesions are precursors to low-grade invasive carcinoma. METHODS: The authors reviewed biopsies containing columnar cell lesions, using the criteria of Schnitt and Vincent-Salomon, from 77 women in the Nashville Breast Cohort who developed subsequent breast carcinoma. Clinicopathologic features including laterality, type, and grade of the subsequent cancer were recorded. RESULTS: Breast cancer developed a median of 11 years after initial biopsy. The median age at diagnosis was 60 years. The majority of invasive carcinomas were of no special type and of intermediate grade. Moreover, the carcinomas were as likely to occur in the contralateral breast as in the breast that was originally diagnosed with columnar cell lesion, regardless of columnar cell lesion subtype (P = .48). CONCLUSIONS: Carcinoma subsequent to columnar cell lesions may occur in either breast and tends to show a similar grade and type distribution as sporadic breast cancer. These findings argue against columnar cell lesions being a true precursor for low-grade invasive carcinoma.

Cutaneous leishmaniasis mimicking inflammatory and neoplastic processes: a clinical, histopathological and molecular study of 57 cases.

BACKGROUND: Cutaneous leishmaniasis displays considerable variation in its histopathological and clinical presentation. Clinically, it progresses from a papule into a painless ulcerated and crusted nodule/papule. Microscopically, it progresses from sheets of amastigote-filled histiocytes to granulomatous inflammation. METHODS: The study was conducted on 145 skin biopsies from untreated patients with histopathological and/or clinical suspicion of cutaneous leishmaniasis in Lebanon, Syria and Saudi Arabia (1992-2010). The pre-biopsy clinical diagnosis and demographic data were collected. Biopsies were evaluated for the major microscopic pattern, and the parasitic index (PI) was also determined. Diagnosis was confirmed by polymerase chain reaction (PCR) followed by molecular sub-speciation. RESULTS: Of the 145 patients, 125 were confirmed as cutaneous leishmaniasis by PCR. Eighteen cases presented with a pre-biopsy clinical diagnosis other than cutaneous leishmaniasis that ranged from dermatitis to neoplasm. Of the 125 cases, 57 showed a major histopathological pattern other than cutaneous leishmaniasis. Identification of amastigotes was equivocal (PI ≤1) in 38 of the 57 cases. Of interest, all the 18 cases with a pre-biopsy clinical diagnosis other than cutaneous leishmaniasis also showed atypical histopathology for cutaneous leishmaniasis. CONCLUSIONS: The manifestations of cutaneous leishmaniasis are broad and may mimic other inflammatory and neoplastic diseases. Pathologists and dermatologists should be aware of such pitfalls and can utilize PCR to confirm the diagnosis of leishmaniasis.

Nerve sheath tumor with degenerative atypia and multivacuolated lipoblasts.

Lipoblastic nerve sheath tumor is a recently described benign soft tissue tumor consisting of lipoblasts in a neural/schwannian background. The 6 reported cases have exclusively comprised signet ring lipoblasts and showed no cellular atypia. The authors describe the first lipoblastic nerve sheath tumor to harbor multivacuolated lipoblasts and degenerative atypia, underscoring its important differential diagnosis with well-differentiated liposarcoma. The purpose of this report is to expand the morphologic spectrum of this unusual neoplasm, and reemphasize the potential of benign nonadipocytic tumors to harbor multivacuolated lipoblasts and mimic liposarcoma.

Verruciform xanthoma: a special epidermal nevus.

Congenital hemidysplasia with ichthyosiform nevus and limb defects (CHILD) syndrome is a rare X-linked hereditary disorder. Presentation varies from ichthyosiform nevus to complete limb amelia. We present a 17-year-old adolescent girl who presented with a 16-cm exophytic mass of the right foot that had been growing for 7 years as well as knee contracture. Deformed nails with onychorrhexis were noted bilaterally. History of multiple nonlinear erythematous skin lesions covered by dry waxy scales involving multiple body folds with sharp midline demarcation was obtained. The patient's family history was negative for consanguinity and similar conditions. Radiography showed right leg hypoplasia and osteopenia. These findings fulfill the diagnosis of CHILD syndrome. Microscopically, psoriasiform epidermal hyperplasia with marked orthohyper-keratosis and neutrophilic exocytosis were noted. The papillary dermis was packed with foamy macrophages consistent with xanthomatous changes, namely verruciform xanthoma. Verruciform xanthoma, although rarely found in other conditions, is a characteristic finding.