Chi K. Lai

Histopathologic findings of HPV and p16 positive HNSCC

Human papilloma virus (HPV) and p16INKa (p16) positivity in head and neck squamous cell carcinomas (HNSCCs) is currently thought to be an encouraging prognostic indicator. However, the histopathologic changes responsible for this behavior are poorly understood. It is our objective to elucidate these histopathologic characteristics to help define the clinical utility of these markers.

Pathology of late-onset anthracycline cardiomyopathy

INTRODUCTIONnAnthracyclines are known to have acute cardiotoxicity. Anthracycline-induced dilated cardiomyopathy may have late onset and present years after administration of the drug. Several studies have described the clinical findings in patients with late-onset cardiomyopathy, including electrocardiography, exercise testing, echocardiography, and histological findings in endomyocardial biopsies; however, there is little information on the pathological changes that are found in explanted or autopsy hearts.nnnMETHODSnWe reviewed the medical records and microscopic slides of heart tissue from one patient who had an autopsy and from nine patients who had cardiac transplants between 2001 and 2008. Heart weights were compared to historic controls (heart weights normalized for the patients heights). Hematoxylin and eosin (H&E)-stained slides were semiquantitated for evidence of necrosis, myocytolysis, interstitial fibrosis, replacement fibrosis, and the presence of inflammation.nnnRESULTSnThe average heart weight ranged from 231 to 470 g (mean=317 ± 65 g, median=303 g). Review of the histological sections revealed no evidence of significant necrosis or myocytolysis. Interstitial fibrosis was identified in all 10 patients, with six patients showing multifocal fibrosis, three patients showing diffuse fibrosis, and only one patient showing focal fibrosis. Replacement fibrosis was identified in six patients, with two patients displaying multifocal and four patients displaying focal replacement fibrosis.nnnCONCLUSIONnLate-onset cardiomyopathy is a serious consequence of anthracycline therapy resulting in death or the need for cardiac transplantation in some patients. Unlike most other forms of dilated cardiomyopathy, the major pathological changes appear to be interstitial and/or replacement fibrosis without significant cardiac hypertrophy.

A novel classification system for perineural invasion in noncutaneous head and neck squamous cell carcinoma: histologic subcategories and patient outcomes

OBJECTIVEnThe aims of this study were to define a novel classification system of tumor perineural invasion (PNI) with respect to tumor/nerve involvement such as intratumoral (IT), peripheral, or extratumoral (ET) and to determine the prognostic significance of each of these histologic subcategories in patients with noncutaneous head and neck squamous cell carcinoma (HNSCC).nnnSTUDY DESIGNnThis study is a retrospective chart review and histologic analysis of patients with HNSCC in the setting of a tertiary care medical center.nnnMETHODSnA clinical chart review of 142 patients with HNSCC who underwent primary surgical treatment from January 2004 through December 2007 was performed. Clinical information collected included patient age, sex, alcohol and tobacco use, tumor location, TNM stage, postoperative adjuvant chemotherapy and/or radiation treatment, and patient outcome. For each case, PNI density, the distance of each PNI focus to the tumor edge, and size of the largest nerve involved were measured. Furthermore, PNI was subcategorized as IT, peripheral, or ET. A Cox regression analysis was performed to determine if PNI was related to regional disease recurrence. Kaplan-Meier survival analysis was also performed.nnnRESULTSnAmong the 142 patients, 37 (26%) had disease progression. The maximum extent of PNI was significantly correlated with disease-free survival on multivariate analysis (P = .019) and was also significantly related to disease-free survival when T stage (P = .017), N stage (P = .021), and T and N stages (P = .02) were added to the Cox regression model. Kaplan-Meier analysis demonstrated a trend toward increased disease-free survival of PNI negative and IT/peripheral PNI compared with ET PNI.nnnCONCLUSIONnPerineural invasion is correlated with nodal status and T stage and is related to disease-free survival. It can be subcategorized as IT, peripheral, or ET. This novel classification system has important implications with regard to clinical outcome and may help define a cohort of patients that may require more aggressive management.

Mucinous adenocarcinomas of the thymus : Report of 2 cases and review of the literature

BackgroundMost adenocarcinomas of the mediastinum are metastatic lesions. Primary thymic adenocarcinomas are extremely rare neoplasms. We could find only 12 cases reported in the literature; of these 12, only 4 were of the mucinous subtype. DesignWe report 2 additional cases of the mucinous subtype, including a previously unreported mucinous variant with numerous psammoma bodies. ResultsThe first case in a 61-year-old woman resembled a mucinous (colloid) carcinoma of other organs such as the breast and colon. It consisted of islands and strips of tumor cells floating in large pools of extracellular mucin. A unique feature of this tumor was the presence of numerous psammoma bodies. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) 7 and negative for CD5. The second case in an 82-year-old woman was a mucinous adenocarcinoma arising from a thymic cyst with areas of transition from benign to dysplastic epithelium. The tumor cells formed dilated glands, cords, and small nests that infiltrated the thymic cyst wall and exhibited evidence of mucin production. Immunohistochemically, the tumor cells were positive for CK 7 and focally positive for both CD5 and CK 5/6. ConclusionsMucinous adenocarcinoma, with or without, psammoma bodies, may be of primary thymic origin and should be considered in the differential diagnosis of malignant mediastinal tumors. These 2 cases provide further documentation of the rare occurrence of primary mucinous adenocarcinomas of the thymic gland.

Snail as a novel marker for regional metastasis in head and neck squamous cell carcinoma.

OBJECTIVEnPrevious studies have shown Snail expression integral to the epithelial-mesenchymal transition during tumor progression. However, its behavior in clinical head and neck squamous cell carcinomas (HNSCCs) is yet undefined. We therefore sought to (1) investigate clinical and histopathologic characteristics of Snail-positive HNSCC and (2) understand the link between Snail and other commonly used HNSCC tumor markers.nnnSTUDY DESIGNnA retrospective case-control study was conducted.nnnSETTINGnThis study was conducted in a large-scale academic center.nnnSTUDY SUBJECTSnOf 51 consecutive HNSCC, 42 surgical resections were included.nnnMETHODSnTwo separate pathologists performed standard histopathologic reviews along with immunohistochemistries (Snail, E-cadherin, p16, epidermal growth factor receptor [EGFR]) and in situ hybridization (human papilloma virus [HPV]). Medical review for all cases was performed.nnnRESULTSnTwenty-two (52%) of 42 cases stained 4+ Snail (>75% staining). The remaining 20 cases were considered negative. Snail was strongly inversely related to E-cadherin expression (ρ = -0.69, P < .001), but statistically independent from HPV, p16, or EGFR expression. Snail(+) tumors were equally represented from each anatomic subsite. Snail(+) tumors were strongly associated with poor differentiation (P < .001) and basaloid classification (P = .004). Snail(+) tumors were also strongly associated with lymphovascular invasion (P = .02), but not perineural invasion. Ultimately, 11 (50%) of 22 of Snail(+) tumors demonstrated positive nodal metastasis and 11 (79%) of 14 node-positive cases were Snail(+) (P = .02).nnnCONCLUSIONnThis pilot study provides promising evidence of Snail role as a molecular prognostic marker for HNSCC. Snail positivity is significantly predictive of poorly differentiated, lymphovascular invasive, as well as regionally metastatic tumors. Because Snail positivity appears independent of HPV, p16, and EGFR expression, Snail may prove to improve upon these markers predictive limitations.

Has the 2004 revision of the International Society of Heart and Lung Transplantation grading system improved the reproducibility of the diagnosis and grading of cardiac transplant rejection

We compared the interobserver reproducibility of the 1990 and 2004 International Society for Heart and Lung Transplantation (ISHLT) grading system for cardiac rejection. The 2004 ISHLT grading system for cardiac allograft rejection did not improve reproducibility partly due to pathologists disagreement in diagnosing Grades 1B/1R and 3A/2R rejection. To achieve better reproducibility, better criteria for defining 1B/1R vs. 3A/2R rejection and markers of myocyte injury are needed.

Adenoid cystic carcinoma of the airway: a 30-year review at one institution

PURPOSEnThe purpose of the study was to evaluate the treatment results of adenoid cystic carcinoma (ACC) of the airway at a single institution during a 30-year period.nnnMATERIALS AND METHODSnAll cases of ACC of the airway over a 30-year period at one tertiary care institution were reviewed retrospectively. The demographics, treatment modalities, pathologic characteristics, and outcomes were evaluated.nnnRESULTSnEleven patients were treated for ACC of the airway with an age range of 25 to 72 years (median, 48 years). Six patients presented with ACC in the larynx, and 5 patients had ACC of the trachea. All patients underwent surgical excision and radiation; 9 of 11 patients had postoperative external beam radiation, 1 patient had preoperative external beam radiation, and the remaining patient had postoperative neutron beam therapy. Four patients with tracheal ACC and none with laryngeal ACC had microscopic or grossly positive margins after surgery (P = .048). Eighty percent of patients had perineural invasion on pathology. Two patients with tracheal ACC had local recurrence of disease, which occurred at 1 and 10 months postoperatively. One patient with laryngeal ACC died of distant metastatic disease at 16 months. Follow-up varied from 4 to 168 months (median, 31 months).nnnCONCLUSIONSnWe report high disease-free survival rates for ACC of the airway in patients who underwent definitive surgical resection followed by postoperative radiation. There is a higher risk for local recurrence and positive surgical margins with distal tracheal location. Distant disease ultimately determines survival.

Characterization of myocardial scars: Electrophysiological imaging correlates in a porcine infarct model

BACKGROUNDnDefinition of myocardial scars as identified by electroanatomic mapping is integral to catheter ablation of ventricular tachycardia (VT). Myocardial imaging can also identify scars prior to ablation. However, the relationship between imaging and voltage mapping is not well characterized.nnnOBJECTIVEnThe purpose of this study was to verify the anatomic location and heterogeneity of scars as obtained by electroanatomic mapping with contrast-enhanced MRI (CeMRI) and histopathology, and to characterize the distribution of late potentials in a chronic porcine infarct model.nnnMETHODSnIn vivo 3-dimensional cardiac CeMRI was performed in 5 infarcted porcine hearts. High-density electroanatomic mapping was used to generate epicardial and endocardial voltage maps. Scar surface area and position on CeMRI were then correlated with voltage maps. Locations of late potentials were subsequently identified. These were classified according to their duration and fractionation. All hearts underwent histopathological examination after mapping.nnnRESULTSnThe total dense scar surface area and location on CeMRI correlated to the total epicardial and endocardial surface scar on electroanatomic maps. Electroanatomic mapping (average of 1,532 ± 480 points per infarcted heart) showed that fractionated late potentials were more common in dense scars (<0.50 mV) as compared with border zone regions (0.51 to 1.5 mV), and were more commonly observed on the epicardium.nnnCONCLUSIONnIn vivo, CeMRI can identify areas of transmural and nontransmural dense scars. Fractionated late diastolic potentials are more common on the epicardium than the endocardium in dense scar. These findings have implications for catheter ablation of VT and for targeting the delivery of future therapies to scarred regions.

Intrapulmonary Ectopic Liver After Orthotopic Heart Transplantation

We report a case of a 54-year-old woman who was found to have multiple intrapulmonary nodules detected on imaging 33 months after orthotopic heart transplantation. Needle biopsy of 2 discrete nodules showed benign hepatic tissue, consistent with intrapulmonary foci of ectopic liver. In this report, the clinical, radiologic, microscopic, and fluorescent in situ hybridization results of 2 biopsied nodules are described. A brief review of the published information on ectopic liver is also presented. To our knowledge, multiple ectopic foci of the liver have never been reported at any site. Furthermore, this is the first reported case that involves a transplant recipient, thereby introducing additional, unique ramifications to this rare but intriguing entity.

Sebaceous adenoma of the parotid gland: a case report with fine needle aspiration findings and histologic correlation.

BACKGROUNDnSebaceous adenoma of the salivary gland is an extremely rare, benign neoplasm that predominantly involves the major salivary glands. The major problem in dealing with sebaceous adenoma is the recognition of this entity to avoid confusion with other more aggressive neoplasms, such as mucoepidenmoid carcinoma. In particular, recognition of this entity in cytologic specimens is important to avoid radical surgery.nnnCASEnA 29-year-old woman presented with an enlarging parotid mass. Fine needle aspiration (FNA) biopsy showed cellular smears composed of sheets and aggregates of cuboidal to low columnar cells with slightly irregular nuclear contours, prominent nucleoli and a moderate amount of cytoplasm that appeared squamoid and finely vacuolated. The FNA was misinterpreted as possible low grade mucoepidermoid carcinoma.nnnCONCLUSIONnWe report a case ofa rare and unusual tumor of the salivary glands. The major problem in dealing with sebaceous adenoma is the recognition ofthis entity in cytologic specimens to avoid confusion with other more aggressive neoplasms such as low grade mucoepidermoid carcinoma and potentially to avoid radical surgery. In this paper, the clinical presentation, pathological findings on the fine needle aspirate and surgical resection specimen, and review of the literature will be discussed.