Aaron F. Sassoon

Immunoreactive neuron-specific enolase, bombesin, and chromogranin as markers for neuroendocrine lung tumors

Sixty-four lung tumors were evaluated for the presence of immunoreactive neuron-specific enolase (NSE), bombesin (Bn), and chromogranin (Cg) to assess their value as markers for neuroendocrine cells in the histologic diagnosis of pulmonary neoplasms. Staining was correlated with the presence and density of neurosecretory granules (number of neurosecretory granules per unit cytoplasmic cross-sectional area) as determined by planimetry on electron micrographs. The cytoplasmic density of neurosecretory granules was significantly greater in the carcinoid tumors than in the small cell carcinomas (P less than 0.001). Neuron-specific enolase was localized in all of the neuroendocrine granule-bearing tumors but was also present in 57 per cent of the nonneuroendocrine carcinomas. Bombesin was present in 68 per cent of the neuroendocrine tumors and in less than 1 per cent of the nonneuroendocrine tumors. Staining for Cg appeared to correlate with the density of neuroendocrine granules, with staining in carcinoid tumors but no staining in small cell anaplastic carcinomas. A panel of antibodies may be required for the reliable identification of neuroendocrine lung tumors by immunohistochemical techniques.

Localized fibrous mesothelioma: An immunohistochemical and electron microscopic study

The absence of keratin staining in tumor cells from localized fibrous mesotheliomas in both paraffin-embedded and frozen sections with sensitive peroxidase-antiperoxidase and avidin-biotin techniques is described. In addition ot the absence of staining for whole-stratum corneum keratin proteins, sections were negative for keratins of different molecular weights (45, 55, and 63 kilodaltons) that are characteristically present in mesothelial cells. Ultrastructurally, the cells most closely resembled mesenchymal cells of the fibroblastic type. These findings are in accordance with recent theories that relate the derivation of localized fibrous mesotheliomas to nonmesothelial cells, including subpleural connective tissue. Based on differences in immunohistochemical staining, the tumors appear to be unrelated to diffuse malignant mesotheliomas.

Distribution of T-cell phenotypic subsets and surface immunoglobulin-bearing lymphocytes in lymph nodes from male homosexuals with persistent generalized adenopathy: An immunohistochemical and ultrastructural study

Lymph nodes from homosexual men with persistent generalized adenopathy were evaluated for distribution of T-cell phenotypic subsets and surface immunoglobulin(SIg)-bearing lymphocytes. Electron microscopy revealed tubulovesicular structures within lymphocytes but no multivesicular rosettes. Eight to 33 per cent of the lymphocytes within germinal centers were suppressor T cells, compared with germinal centers from control lymph nodes, in which these cells were rare (P = 0.002). Significantly greater percentage of suppressor/cytotoxic T lymphocytes were also present in the paracortex and follicular mantles of lymph nodes from the homosexual group (P = 0.002 and 0.007, respectively). Percentages of helper T lymphocytes were significantly decreased in germinal centers (P = 0.008) and paracortical regions (P = 0.002). Florid follicular hyperplasia with aberrations in follicular architecture was the most common histologic pattern, but one node with diffuse hyperplasia and subtotal effacement of architecture revealed depletion of SIg-bearing lymphocytes and increased numbers of suppressor T cells. Reversed helper-to-suppressor T-cell ratios in lymph nodes from homosexuals with generalized adenopathy may be related to viral infection and contribute to immune deficiency in this group.

Peripheral T cell lymphoma (immunoblastic sarcoma of T cell type): An immuno-ultrastructural study

Use of monoclonal antibodies directed against T cell antigens for the phenotypic characterization of neoplastic lymphoid cells in peripheral T cell lymphomas is described. Studies of cryostat sections revealed the distribution of T cell subsets in nodal and extranodal infiltrates, and immuno-ultrastructural techniques demonstrated discrete localization of T cell antigens to the cytoplasmic membranes of neoplastic cells. Although histologically similar, the tumors appeared heterogeneous as to their immunologic phenotype, with the majority demonstrating markers for T helper/inducer lymphocytes.

Involucrin in intraepithelial and invasive squamous cell carcinomas of the cervix: An immunohistochemical study

Immunohistochemical staining for involucrin, a cytoplasmic protein synthesized during squamous maturation, was assessed in histologic sections from hysterectomy and cone biopsy specimens from patients with cervical neoplasia. In normal and condylomatous squamous epithelium, diffuse cytoplasmic staining was seen in the suprabasal layers, with no staining of the basal cells. Staining was absent in two cases of cervical intraepithelial neoplasia (CIN), grade III, in which the lesions were composed entirely of undifferentiated cells and markedly decreased in cases involving large numbers of basal cells. In 19 of 23 cases (83 per cent) of CIN, however, focal staining for involucrin was seen in large differentiated cells in the more superficial layers, and in two cases of keratinized CIN diffuse suprabasal staining was observed. Similarly, strong staining for involucrin was present in differentiated areas in one case of microinvasive squamous cell carcinoma and in 93 per cent of cases of infiltrating squamous cell carcinoma. These findings suggest that involucrin is a marker for maturation in cervical squamous epithelial neoplasms. Patterns of immunohistochemical staining for involucrin in keratinized dysplasia and differentiated squamous carcinomas should be taken into consideration if loss of involucrin staining is used as a criterion for neoplastic transformation of cervical epithelium, as has been proposed.

Successful Treatment of Genetically Profiled Pediatric Extranodal NK/T‐Cell Lymphoma Targeting Oncogenic STAT3 Mutation

Extranodal natural killer (NK)/T‐cell lymphoma (ENKTCL) is a distinct type of non‐Hodgkin lymphoma predominantly observed in Asian and Latin American adult males. A 12‐year‐old Hispanic female diagnosed with ENKTCL was enrolled in our genomic profiling research protocol. We identified specific somatic alterations consistent with diagnosis of ENKTCL as well as oncogenic mutations in MAP2K1 and STAT3. To our knowledge, this is the first report of an immunophenotypically confirmed and genetically profiled case of ENKTCL in a female pediatric patient in the United States, including its unique treatment and favorable outcome.

Abstract PR06: Precision medicine for newly diagnosed and refractory/recurrent pediatric cancer patients: Lessons learned from “N=1” studies

Whole genome sequencing has rapidly emerged as the preferred method for unbiased genomic interrogation. Leveraging this technology, we have developed a precision medicine clinical research protocol for pediatric, adolescent, and young adult cancer patients. The primary objective of this study is to arrive at genome informed treatment recommendations for individual patients suffering from aggressive and/or worsening disease in a clinically relevant time frame. The second objective is to survey the genomic landscape of newly diagnosed and recurrent/refractory patients. To accomplish this, we have employed an interdisciplinary workflow including a customized bioinformatic analysis pipeline, contextual biological interpretation of the data, and case reviews during weekly molecular tumor board meetings. Here we report the results of having sequenced over 50 patients diagnosed with both common and rare malignancies. Factors affecting the successful identification of therapeutically actionable targets and subsequent intervention are varied. The most consistent findings are the increased mutation burden in patients who have received chemotherapy and/or radiation prior to tissue collection. Lastly, we highlight the realistic opportunities, challenges, and insight gained from an ongoing single institution experience. This abstract is also presented as Poster 27. Citation Format: Troy A. McEachron, Keri B. Zabokrtsky, Aaron F. Sassoon, Sara Nasser, Tyler Izatt, Chad P. Garner, David W. Craig, John D. Carpten, Leonard S. Sender. Precision medicine for newly diagnosed and refractory/recurrent pediatric cancer patients: Lessons learned from “N=1” studies. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr PR06.

Abstract A42: Precision medicine for pediatric, adolescent, and young adult patients with newly diagnosed or refractory/recurrent cancer: Lessons learned from N=1 studies on rare tumors

Next-generation sequencing has rapidly emerged as the preferred method for unbiased genomic interrogation and is increasingly being integrated into clinical practice. Utilizing this technology, we have developed a precision medicine clinical research protocol focused on pediatric, adolescent, and young adult (AYA) patients with cancer. Our objectives are two-fold: 1) To arrive at genome informed treatment recommendations for individual patients suffering from aggressive and/or worsening disease in a clinically relevant time-frame; 2) To survey the genomic landscape of patients with newly diagnosed and/or recurrent/refractory disease. To accomplish this, we have employed an interdisciplinary workflow including a customized bioinformatic analysis pipeline, contextual biological interpretation of the data, and case reviews during regularly scheduled molecular tumor board meetings. To date we have sequenced over 50 patients. Here, we present the data from those patients diagnosed with rare malignancies. Factors affecting the successful identification of actionable targets and subsequent intervention are varied. Furthermore, we highlight the realistic opportunities, challenges, and insight gained from an ongoing single institution experience. Citation Format: Troy A. McEachron, Keri B. Zabokrtsky, Aaron Sassoon, Zarko Manoljvic, David W. Craig, John D. Carpten, Leonard S. Sender. Precision medicine for pediatric, adolescent, and young adult patients with newly diagnosed or refractory/recurrent cancer: Lessons learned from N=1 studies on rare tumors. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr A42.