Monica T. Garcia-Buitrago

p16INKa Immunocytochemistry in Fine-Needle Aspiration Cytology Smears of Metastatic Head and Neck Squamous Cell Carcinoma

Objectives: Patients with head and neck squamous cell carcinoma (HNSCC) may initially present with neck metastases diagnosed by fine-needle aspiration (FNA). In these patients, it is critical to locate the primary site so that targeted therapy can be administered. Nearly a quarter of HNSCC are associated with human papillomavirus (HPV) infection. The great majority of HPV-related primaries originate in the oropharynx. p16INKa (p16) functions as a surrogate marker of HPV infection. We sought to determine if expression of p16 by immunocytochemistry (ICC) in neck metastases could assist in localizing the primary site to the oropharynx. Study Design: Diagnostic FNA cytology smears of neck metastases from 90 patients with biopsy-proven primary HNSCC were reviewed. Papanicolaou-stained slides were directly subjected to ICC, using p16 antibody. Results: Twenty-seven (30%) tumors expressed p16 by ICC; 74% of these p16-positive tumors were metastases from oropharynx. There was a significantly higher proportion of p16 expression in patients with primary oropharyngeal carcinoma (47%) versus those whose primary tumor was non-oropharyngeal (15%; p = 0.0013). Conclusions: p16 expression in FNA cytology smears of metastatic HNSCC is a useful indicator of oropharyngeal origin and can be used to help localize the primary site in cases where this is not clinically evident.

BK virus nephropathy in a pediatric heart transplant recipient with post-transplant lymphoproliferative disorder: a case report and review of literature.

BKV is known to cause allograft failure in kidney transplant recipients. It has been recently recognized to cause native kidney nephropathy in non‐kidney transplant recipients. This is a case report BKVN in a 15‐yr‐old HTx recipient who had PTLD and a review of pediatric cases in the literature. The patient was diagnosed with BKVN +189 months after transplantation and died thirty days after diagnosis of BKVN. We identified five other cases of BKVN in pediatric non‐kidney solid organ transplantation, of which all were HTx recipients. Overall, outcome was poor and BKV clearance was not achieved with reduction of immunosuppression and with current therapies. We strongly recommend that pediatric HTx recipients be tested for BKV infection if there is evidence of kidney dysfunction. We also recommend that they have an annual screening for BKV viruria and viremia with the assessment of kidney function.

An immunohistochemical panel to distinguish ovarian from uterine serous papillary carcinomas.

Serous papillary carcinomas (SPCs) share a similar morphology regardless of whether they originate from the ovary or the uterus. Identification of the site of origin of the tumor can be a challenging and a diagnostic dilemma, particularly, in the setting of a pelvic mass or peritoneal carcinomatosis. Recognition of the site of origin influences the staging, management, and prognosis of these malignancies. The purpose of this study is to identify a panel of markers to distinguish the ovarian serous papillary carcinomas (OSPC) from the uterine serous papillary carcinomas (USPC). Formalin-fixed, paraffin-embedded archival tissue from 46 cases of SPCs (33 uterine and 13 ovarian) were stained using antibodies for estrogen receptor (ER), WT1, insulin-like growth factor-II mRNA-binding protein 3 (IMP3), p53, and p16. The OSPC expressed ER (92%), WT1 (100%), IMP3 (92%), p53 (92%), and p16 (92%). The USPCs expressed ER (30%), WT1 (64%), IMP3 (85%), p53 (64%), and p16 (76%). Only ER expression was significantly higher in OSPC compared with USPCs (P<0.001). The combined ER+WT1+ phenotype was present in 92% of the OSPC, whereas only 18% of the USPCs had the same phenotype (P<0.001). Furthermore, 71% of the OSPCs expressed ER+, p53+, WT1+, IMP3+, and p16+ immunophenotype, whereas in USPCs, the tumor cells showed immunophenotypic diversity, with only 6% of the USPCs expressing reactivity to all the 5 markers (P<0.001). This study suggests that ER alone or in combination with a limited panel of markers may be used to identify the site of origin of SPCs.

Small-cell cancer of the breast: what is the optimal treatment? A report and review of outcomes.

Introduction Primary small-cell cancer of the breast, also known as oat cell carcinoma or neuroendocrine carcinoma of the breast, is a rare disorder with only a few cases reported in the literature since its first description by Wade et al in 1983. Little is known on the optimal treatment and outcomes and a wide variety of treatments, including surgery, chemotherapy, and radiation have been used with different outcomes.

A child with BK virus infection: Inadequacy of current therapeutic strategies

Pereira T, Rojas CP, Garcia‐Buitrago MT, Chandar J, Abitbol C, Seeherunvong W, Rusconi P, Bruce JH, Zilleruelò G. A child with BK virus infection: Inadequacy of current therapeutic strategies. 
Pediatr Transplantation 2011.

In silico and Ex vivo approaches identify a role for toll-like receptor 4 in colorectal cancer

BackgroundInflammation increases the risk of colorectal cancer (CRC). We and others have described a role for TLR4, the receptor for LPS, in colon cancer. To explore the relationships between TLR4 expression and CRC, we combined the strength of transcriptome array data and immunohistochemical (IHC) staining.MethodsTLR4 signal intensity was scored in the stromal and epithelial compartments. Detection of differential expression between conditions of interest was performed using linear models, Cox proportional hazards models, and empirical Bayes methods.ResultsA strong association between TLR4 expression and survival was noted, though a dichotomous relationship between survival and specific TLR4 transcripts was observed. Increasing TLR4 expression was seen with advancing tumor stage and was also over-expressed in some adenomas. IHC staining confirmed the positive relationship between TLR4 staining score in the CRC tumor stroma and epithelium with tumor stage, with up to 47% of colon cancer stroma positive for TLR4 staining. Increased TLR4 expression by IHC was also marginally associated with decreased survival. We now also describe that pericryptal myofibroblasts are responsible for a portion of the TLR4 stromal staining.ConclusionsIncreased TLR4 expression occurs early in colonic neoplasia. TLR4 is associated with the important cancer-related outcomes of survival and stage.

High-Risk Human Papillomavirus DNA Detected in Primary Squamous Cell Carcinoma of Urinary Bladder

CONTEXT We reported previously that more than one-third (37%) of primary bladder squamous cell carcinomas (SCCs) demonstrate diffuse p16 immunoreactivity independent of gender. This observation made us question whether p16 overexpression in bladder carcinoma is due to human papillomavirus (HPV)-dependent mechanisms. OBJECTIVES To determine whether the presence of high-risk HPV (HR-HPV) DNA could be detected in these tumor cells. DESIGN Fourteen cases of primary bladder SCC, which were positive for p16 by immunohistochemistry, were probed for the detection of HR-HPV by in situ hybridization and the signal amplification Invader assay. Samples positive for detection of HR-HPV by Invader assay were amplified by using HR-HPV type-specific primers, and amplification products were DNA sequenced. RESULTS Detection of HR-HPV by the in situ hybridization method was negative in all cases (0 of 14). However, in 3 of 14 cases (21.4%), the presence of HR-HPV DNA was detected with the Cervista HPV HR Invader assay, which was followed by identification of genotype. All positive cases were confirmed by using HR-HPV type-specific amplification followed by DNA sequencing. Identified HR-HPV genotypes included HPV 16 (2 cases) and HPV 35 (1 case). CONCLUSIONS High-risk HPV DNA is detectable in a subset of primary bladder SCCs. Based on the well-documented carcinogenic potential of HR-HPV, there is a necessity for additional studies to investigate the role of HR-HPV in bladder carcinogenesis.

A Case of a Ruptured Sclerosing Liver Hemangioma

Hemangiomas are the most common benign tumors found in the liver, typically asymptomatic, solitary, and incidentally discovered. Although vascular in nature, they rarely bleed. We report a case of a 52-year-old woman with a previously stable hemangioma who presented to our hospital with signs and symptoms indicative of spontaneous rupture. We review the literature, focusing on diagnosis and management of liver hemangiomas.

Irreversible Electroporation of Hepatic and Pancreatic Malignancies: Radiologic-Pathologic Correlation

Irreversible electroporation (IRE) is a novel therapy that has shown to be a feasible and promising alternative to conventional ablative techniques when treating tumors near vital structures or blood vessels. The clinical efficacy of IRE has been evaluated using established imaging criteria. This study evaluates the histologic and imaging response of hepatic and pancreatic malignancies that were surgically resected after IRE. In total, 12 lesions ablated with IRE were included, including 3 pancreatic carcinomas, 5 primary tumors of the liver, and 4 metastatic tumors of the liver. The rate of complete response to IRE was 25% based on the histologic evaluation of the resected tumors. Although treatment-related vessel wall changes were noted in several cases in histologic findings, there was no evidence of vascular luminal narrowing or obliteration in any of the specimens. The imaging response to IRE before surgical resection usually resulted in underestimation of disease burden when compared with the histologic response seen on the resected specimens.

The immune system and gastrointestinal stromal tumor: a wealth of opportunities

Purpose of review This article reviews the current literature on tumor-infiltrating immune cells in gastrointestinal stromal tumor (GIST), and the current status and prospects of effective immunotherapeutic strategies. Recent findings Tumor-infiltrating immune cells populate the microenvironment of GISTs; the most numerous are tumor-associated macrophages (TAMs) and CD3+ T cells. TAMs have not been shown to have a relationship with the biological behavior of GISTs; however, the number of CD3+ T cells correlates with better outcomes. The prognostic significance of tumor-infiltrating neutrophils, natural killer cells, CD4+ T cells, CD8+ T cells, and Treg cells remains unknown. Imatinib mesylate achieves a clinical response in 80% of patients with GIST. Its antitumor mechanism is partially immune mediated. The combination of imatinib and interferon-&agr; has been shown to be effective against GIST – it eradicates tumor cells including those that are drug resistant. Preclinical trials including cytotoxic T lymphocyte-associated antigen 4 blockade, anti-KIT antibody, and the generation of designer T cells have shown promising therapeutic effect in animal models of GIST. Summary GIST contains many tumor-infiltrating immune cells and should be susceptible to immunotherapy; early clinical and preclinical trials have shown promising results that should lead to new investigations and effective forms of direct and synergistic therapies.