To evaluate the performance characteristics of PD-L1 immunohistochemistry (IHC) combined positive scoring (CPS) in core biopsies and aspirate cell blocks from patients with head and neck squamous ...cell carcinoma (HNSqCCa). PD-L1 IHC using the SP263 antibody was performed on 20 paired cases which consisted of a small biopsy and an excisional specimen. The scores were compared at both the 1% and 20% cutpoints. Using the CPS result obtained from the resected specimen or excisional biopsy as the gold standard, PD-L1 IHC performed on the core biopsy or cell block identified 4 of 6 positive cases (66%) at the 20% cutpoint and 12 of 17 (70%) positive patients at the 1% cutpoint. False positive cases were uncommon at both cutpoints. CPS scoring should be used with caution in small biopsies from patients with HNSqCCa. A negative result should prompt consideration of an excisional biopsy and repeat testing.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Most endometrial cancers are detected early and have a good prognosis, while some endometrial cancers are highly invasive, metastasize early, and respond suboptimally to therapy. Currently, ...appropriate model systems to study the aggressive nature of these tumors are lacking. The objective of this study was to establish a mouse xenograft model of endometrial tumors derived from patients in order to study the biological aggressive characteristics that underlie invasion and metastasis.
Endometrial tumor tissue fragments (1.5 mm × 1.5 mm) from patients undergoing surgery, were transplanted under the renal capsule of NOD scid gamma mice. After 6-8 weeks, tumors were excised and serially transplanted into additional mice for propagation. Immunohistochemical analysis of the tumors was done for various tumor markers.
Four cases of different subtypes of endometrial cancer were grown and propagated in mice. Three of the four tumor cases invaded into the kidneys and to adjacent organs. While all tumors exhibited minimal to no staining for estrogen receptor α, progesterone receptor staining was observed for tumor grafts. In addition, levels and localization of E-cadherin, cytokeratin and vimentin varied depending on subtype. Finally, all tumor xenografts stained positively for urokinase plasminogen activator while 3 tumor xenografts, which showed invasive characteristics, stained positively for urokinase plasminogen activator receptor.
Endometrial tumors transplanted under the renal capsule exhibit growth, invasion and local spread. These tumors can be propagated and used to study aggressive endometrial cancer.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Human papillomavirus (HPV) is an important cause of head and neck squamous cell carcinoma (HNSCC) and accounts for a large majority of new cases. The purpose of this study is to determine whether ...there is an association between nodal calcification and HPV positivity in the setting of metastatic HNSCC.
Consecutive patients with HNSCC who underwent CT were retrospectively identified. Patients were then divided into two groups: those with HPV-positive HNSCC and those with HPV-negative HNSCC. Demographic, clinical, and CT data were compared between the two groups to determine factors associated with HPV-positive HNSCC.
A total of 179 patients with HNSCC were included in the final analyses, 104 (58%) of whom had HPV-positive tumors. Univariate analyses demonstrated that those with HPV-positive HNSCC were more likely to have calcified lymph nodes (p = 0.044). Analyses also confirmed previously known associations with male gender (p = 0.001), primary oropharyngeal tumors (p < 0.001), and cystic lymph nodes (<0.001). The HPV-positive HNSCC group was also less likely to have necrotic lymph nodes (p < 0.001).
In addition to known clinical and imaging factors associated with HPV-positive metastatic HNSCC, such as male gender, oropharyngeal primary location, and cystic lymph nodes, the presence of calcifications within cervical lymph nodes, although infrequent, provides an additional useful feature to predict HPV positivity in HNSCC. Additionally, if calcified lymph nodes are present, then a primary oropharyngeal tumor site should be considered.
•In head and neck SCC, the presence of calcifications within cervical lymph nodes may help predict HPV/P16 positivity.•HPV is an important cause of head and neck SCC and accounts for a large majority of new cases.•Known factors of HPV-positive head and neck SCC include an oropharyngeal primary tumor and cystic lymph nodes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Cervical cancer epitomizes the success of cancer prevention through the human papillomavirus (HPV) vaccine, but significant challenges remain in the treatment of advanced disease. We report ...the first three cases of cervical carcinoma harboring an FGFR3 – TACC3 fusion, which serves as a novel therapeutic target. The fusion, identified by comprehensive genomic profiling, activates the FGFR pathway that has been implicated in HPV-driven carcinogenesis. One of the patients whose tumor contained the FGFR3 – TACC3 fusion was treated with an investigational FGFR tyrosine kinase inhibitor. Concomitant molecular alterations involving the PI3K/AKT/mTOR and RAF/MEK pathways were also identified and suggest other treatment strategies that deserve investigation. This case series highlights the role of comprehensive genomic profiling in the identification of new therapeutic targets and in targeted therapy selection for patients with cervical cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cardiac papillary fibroelastoma, a rare entity, is the second most common benign primary cardiac tumor. Commonly involving the cardiac valves, this entity is increasingly diagnosed using different ...imaging modalities. We present a rare case of simultaneous involvement of both the aortic and pulmonary valves in an asymptomatic patient who underwent different imaging modalities, including transthoracic and transesophageal echocardiography, nongated and gated computed tomography, and magnetic resonance imaging. We will discuss the imaging findings and differential diagnosis.
The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into ...three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
ABSTRACTThe treatment of non–small cell lung carcinoma has undergone a paradigm shift over the last decade. Treatment with targeted agents is now the standard of care for many patients. Consequently, ...precise histological typing and triage of tissue for molecular testing are vital components of the pathologic evaluation of small biopsies from these patients. The indications for 2 commonly used chemotherapeutic agents, premetrexed and bevacizumab, are linked to histological subtype in that the use of these agents is contraindicated in cases of squamous cell carcinoma. Treatment with endothelial growth factor receptor or ALK inhibitors is mandated by the current National Comprehensive Cancer Network guidelines for patients with metastatic disease whose tumors harbor these respective mutations. Although molecular testing at most institutions is done using single-gene tests, migration to multiplex assays is likely to occur in the near term to midterm as additional Food and Drug Administration–approved targeted therapies become available. In most venues, formalin-fixed paraffin-embedded tissue is most suitable for biomarker testing and can be reliably generated from many cytology specimens.
Cervical intraepithelial neoplasia (CIN) 2 is an equivocal diagnosis, with p16 immunohistochemical positivity currently recommended for diagnostic confirmation. Biomarkers characteristic of ...squamocolumnar junction cells were recently found to be positive in almost all CIN 2 and CIN 3. CIN 1 lesions which express squamocolumnar junction markers (in particular cytokeratin 7 CK7) are associated with a higher rate of subsequent high-grade squamous intraepithelial lesion, suggesting that CK7 may be a useful prognostic biomarker for CIN 1. We sought to determine the utility of CK7 as a prognostic biomarker in the setting of morphologic CIN 2, and to compare this to the utility of p16 in this setting. We performed CK7 immunohistochemical on 116 cases originally diagnosed as CIN 2. Of these, 68.1% were p16 and 90.5% were CK7. A total of 19.5% of patients had a subsequent diagnosis of CIN 3 on biopsy or excision; the index CIN 2 lesion was CK7 in all of these cases (sensitivity 100%) and p16 in all but 1 (21/22; sensitivity 95.5%). The specificity of p16 (37.4%) and CK7 (8.0%) for predicting subsequent CIN 3 were significantly different (P<0.001). While p16 expression was significantly associated with subsequent CIN 3 (P=0.002), CK7 expression was not (P=0.202). We conclude that CK7, unlike p16, is not useful as a prognostic biomarker in CIN 2. While it is still promising as a prognostic marker in CIN 1, additional studies are needed to determine optimal staining/interpretation criteria.
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