Conrad Schuerch

Overexpression of phosphorylated nuclear factor-kappa B in tonsillar squamous cell carcinoma and high-grade dysplasia is associated with poor prognosis

Intracellular signals along the epidermal growth factor receptor (EGFR)–Akt–nuclear factor-kappa B (NF-κB) pathway have been associated with carcinogenesis in various malignant neoplasms. This investigation was to evaluate the expression of EGFR, phosphorylated(p)-Akt and p-NF-κB and correlate them with clinical outcomes in patients with squamous cell carcinoma of the tonsil. A total of 45 patients with squamous cell carcinoma of the tonsil were studied by immunohistochemistry to evaluate the expression levels of EGFR, p-Akt and p-NF-κB. Results for squamous cell carcinoma of the tonsil were compared with those for associated high-grade dysplasia and adjacent normal appearing epithelium, when present. In addition, tonsillar epithelium from non-neoplastic specimens of age-matched patients also was stained for the same markers. High-grade dysplasia and squamous cell carcinoma of the tonsil demonstrated a similar pattern of expression, which differed from the pattern seen in the adjacent normal epithelium and tonsillar epithelium from normal controls (an overexpression for each of these three protein analytes in high-grade dysplasia and squamous cell carcinoma of the tonsil as demonstrated by immunohistochemistry). When markers from squamous cell carcinoma of the tonsil were correlated with survival status, only increasing levels of p-NF-κB immunoreactivity (a relative overexpression) were statistically significant predictors of poor survival. No markers in squamous cell carcinoma of the tonsil were significantly related to rate of recurrence. When analyzing marker scores from tissue with high-grade dysplasia, relative overexpressions of both p-Akt and p-NF-κB were significantly related to poor survival. Additionally, increasing levels of p-NF-κB immunopositivity from tissue with high-grade dysplasia were also significantly related to rate of recurrence. In summary, p-NF-κB, overexpressed in high-grade dysplasia and squamous cell carcinoma of the tonsil, is associated with worse prognosis in terms of high recurrence and poor survival, respectively. This significant finding in patients with squamous cell carcinoma of the tonsil, in combination with previous animal and in vitro studies, suggests that p-NF-κB represents a potential therapeutic target in head and neck squamous cell carcinoma.

Plasmablastic Lymphoma of the Cervical Lymph Nodes in a Human Immunodeficiency Virus–Negative Patient: A Case Report and Review of the Literature

We report a case of plasmablastic lymphoma presenting in cervical lymph nodes in an 82-year-old, human immunodeficiency virus-negative man. Cytologic and histologic examinations demonstrated a large cell lymphoma with plasmacytic differentiation. The tumor cells were positive for CD138, CD38, epithelial membrane antigen, CD30, and lysozyme, but lacked expression of leukocyte common antigen, T-cell, and B-cell markers. Abundant Epstein-Barr virus-encoded RNA transcripts were identified by in situ hybridization. A monoclonal rearrangement of kappa-light- chain gene was demonstrated. The cytologic, histologic, immunohistochemical, and molecular features of plasmablastic lymphoma are reviewed. The potential diagnostic pitfalls and differential diagnoses, especially in a fine-needle aspiration specimen, are addressed.

Diagnostic utility of S100P and von Hippel-Lindau gene product (pVHL) in pancreatic adenocarcinoma-with implication of their roles in early tumorigenesis.

Recently, we demonstrated von Hippel-Lindau gene product (pVHL) was expressed in normal pancreatic ducts but absent in pancreatic ductal adenocarcinoma (PDA). Previous studies have suggested the diagnostic value of S100P, S100A4, and S100A6 in PDA. In this study, we evaluated pVHL, S100P, S100A4, and S100A6 as potential markers for PDA, pancreatic intraepithelial neoplasia (PanIN), ampullary adenocarcinoma (AAD), and cholangiocarcinoma (CC). Immunostains were performed on 56 PDA cases, 20 AAD cases, and 28 CC cases using antibodies against pVHL, S100P, S100A6, and S100A4. Western blots were also performed on 2 cases of PDA and the matching non-neoplastic pancreatic tissues. Of the 56 PDA cases, immunoreactivity for S100P, S100A6, and S100A4 was observed in 56, 55, and 41 cases, respectively. Non-neoplastic ductal epithelium was negative for S100P in all cases. Ninety percent of PanINs were also positive for S100P. pVHL was not detected in all PDAs and 96% of PanINs by immunohistochemistry. S100P, S100A4, and S100A6 were present in a significant number of AADs and CCs; and pVHL expression was observed in 25% of AADs and 21% of CCs. Our data indicate that (1) S100P and pVHL are a pair of sensitive and specific markers for identifying primary PDA and PanIN; (2) up-regulation of S100P and down-regulation of pVHL may play a role in early tumorigenesis in PDA; and (3) the 4 markers studied have limited value in differentiating among PDA, AAD, and CC.

Immunohistochemical Detection of the von Hippel-Lindau Gene Product (pVHL) in Human Tissues and Tumors A Useful Marker for Metastatic Renal Cell Carcinoma and Clear Cell Carcinoma of the Ovary and Uterus

Genetic alteration of the von Hippel-Lindau (VHL) tumor suppressor gene has been linked to hereditary and sporadic clear cell renal cell carcinomas (RCCs). Inconsistent data on immunodetection of the VHL gene product (pVHL) in normal tissues and tumors have been reported. We immunohistochemically reevaluated the usefulness of a specific rabbit polyclonal anti-pVHL antibody in 531 cases of renal and nonrenal neoplasms and normal tissues. Positive immunostaining was observed in nearly 100% of primary renal neoplasms, 95% of metastatic RCCs, and 90% of clear cell carcinomas of the ovary and uterus. In normal tissues, positive immunoreactivity was observed only in renal tubules, exocrine pancreas, islets, and bile ducts. Western blot and reverse transcription-polymerase chain reaction confirmed the immunostaining results. These data indicate that this anti-pVHL antibody is a useful marker in assisting diagnosis of metastatic RCC and may serve as a diagnostic marker for clear cell carcinomas of the ovary and uterus.

Immunohistochemical detection of P504S in primary and metastatic renal cell carcinomas

P504S/α-methylacryl CoA racemase has been shown to be a relatively sensitive and specific positive marker for prostatic adenocarcinoma. The potential utility of P504S in renal cell neoplasms has not been explored in a large series. We assessed the diagnostic value of P504S in 332 cases of nonprostatic neoplasms using the avidin-biotinperoxidase complex technique, including 115 renal neoplasms, 28 metastatic renal cell carcinomas (RCCs), and 189 nonrenal neoplasms. The results demonstrated that a granular, cytoplasmic staining pattern for P504S was observed in 48 of 70 (68.6%) conventional (clear cell) RCCs, 15 of 15 (100%) papillary RCCs, 2 of 7 (29%) chromophobe RCCs, and 2 of 8 (25%) oncocytomas. Among the 70 cases of clear cell RCC, positivity of P504S was seen in 40%, 71%, 94%, and 75% of RCCs with Furhman nuclear grade I, II, III, and IV, respectively. Strong immunostaining was present in each case (86/86) in the proximal tubules adjacent to the renal neoplasm. Eighty-two percent of metastatic RCCs (23/28) were positive for P504S. However, only 24 of 189 (13%) nonrenal malignancies were positive. The 24 positive cases included 12 of 13 (92%) colorectal adenocarcinomas, 6 of 30 (20%) ductal carcinomas of the breast, and 4 of 23 (17%) adenocarcinomas of the lung. These findings suggest that P504S is a useful marker in diagnosing primary and metastatic RCCs, although it has little value in differentiating chromophobe RCC from oncocytoma.

Histiocytic sarcoma in the small intestine : A case report with flow cytometry study and review of the literature

We describe a case of true histiocytic sarcoma (HS) with features of HS in clinical manifestation, histological presentation, and immunohistochemical panels. The flow cytometry studies were used for the diagnosis. The tumor presents in the small intestine with involvement of regional mesenteric lymph nodes of a 68-year-old female. Histological examination reveals that tumor cells are large and pleomorphic. They have vesicular chromatin and abundant eosinophilic cytoplasm. Immunohistochemical studies show the tumor cells to be positive for CD45 (LCA), CD45RO, CD4, CD68, and lysozyme; and negative for all other T-, B-, macrophage, follicular dendritic- and hematopoietic-cell markers. Proliferation rate is 5% by MIB stain. Flow cytometry studies reveal large atypical cells positive for CD4, CD14, and CD45. There are 29 cases of HS reported in the literature since 2001. All of these cases are summarized. The diagnostic methods and the possible prognostic factors are discussed. We believe that the correct diagnosis of HS is important for clinical treatment and prognostic prediction, although it is very rare.

Lymphocyte Subsets and Activation Antigens in a Reference Population: A Flow Cytometric Study Using Single and Double Antibody Staining

The transferrin receptor (TR), the HLA DR antigen (DR), and the antigen binding OKT10 (T10) are present on activated lymphocyte populations. The authors have studied their expression and that of antigens defined by eight commercial monoclonal antibodies on peripheral blood lymphocytes of 50 healthy hospital workers aged 23-60 years. A whole blood lysis technique was employed and cells were enumerated on a flow cytometer. The percentage of cells bearing the three activation antigens were generally low: mean values for T10 being 7.2%; for TR 1.8%; and for DR 8.8%. There was, however, considerable variability, with occasional subjects having 20% or more cells positive for one of the three antigens. High values of one activation antigen did not correspond with high values of another in the same subject. Nor was there correlation of the presence of activation antigens with the occurrence of cells bearing T11, T4, T8, Leu 1, Leu 2a, Leu 3a, or Leu 7. Double labelling with the following pairs of fluorescein (FITC) and phycoerythrin (PE) labeled antibodies: Leu 2a, DR; Leu 3a, DR; Leu 3a, Leu 2a; TR, DR, indicated that simultaneous expression of the corresponding antigens do not normally occur on lymphocytes of healthy individuals. Double labelling with B1 and DR in five subjects indicated the presence of B1 (+) DR (-) cell population. No pattern of relationship could be detected among common clinical variables or HLA type and an increased expression of activation antigens.

Salivary Gland and Other Head and Neck Structures

This chapter is designed as an easy reference for the practicing pathologist aiming to solve diagnostic problems in head and neck pathology by immunohistochemistry (IHC). It is a collection of 38 practical tables including tables for commonly used antibodies, IHC reactions in normal salivary gland, IHC reactions in common salivary gland and head and neck tumors, and IHC reactions to resolve differential diagnostic challenges. Also included are practical footnotes and photographic illustrations.