Poor Prognosis Indicated by Venous Circulating Tumor Cell Clusters in Early-Stage Lung Cancers.

Early detection of metastasis can be aided by circulating tumor cells (CTC), which also show potential to predict early relapse. Because of the limited CTC numbers in peripheral blood in early stages, we investigated CTCs in pulmonary vein blood accessed during surgical resection of tumors. Pulmonary vein (PV) and peripheral vein (Pe) blood specimens from patients with lung cancer were drawn during the perioperative period and assessed for CTC burden using a microfluidic device. From 108 blood samples analyzed from 36 patients, PV had significantly higher number of CTCs compared with preoperative Pe (P < 0.0001) and intraoperative Pe (P < 0.001) blood. CTC clusters with large number of CTCs were observed in 50% of patients, with PV often revealing larger clusters. Long-term surveillance indicated that presence of clusters in preoperative Pe blood predicted a trend toward poor prognosis. Gene expression analysis by RT-qPCR revealed enrichment of p53 signaling and extracellular matrix involvement in PV and Pe samples. Ki67 expression was detected in 62.5% of PV samples and 59.2% of Pe samples, with the majority (72.7%) of patients positive for Ki67 expression in PV having single CTCs as opposed to clusters. Gene ontology analysis revealed enrichment of cell migration and immune-related pathways in CTC clusters, suggesting survival advantage of clusters in circulation. Clusters display characteristics of therapeutic resistance, indicating the aggressive nature of these cells. Thus, CTCs isolated from early stages of lung cancer are predictive of poor prognosis and can be interrogated to determine biomarkers predictive of recurrence. Cancer Res; 77(18); 5194-206. ©2017 AACR.

MYC immunohistochemistry in angiosarcoma and atypical vascular lesions: practical considerations based on a single institutional experience.

Angiosarcoma (AS) is an uncommon vascular malignancy with an aggressive clinical course. Radiation-associated angiosarcoma (RAAS) and Stewart-Treves syndrome are associated with MYC gene amplification and protein overexpression, while other radiation-associated vascular lesions including atypical vascular lesions (AVL) are not associated with MYC overexpression. In contrast, de novo AS represent a group of molecularly heterogeneous tumours, for which MYC expression has not been extensively examined. In this study, MYC immunohistochemistry (IHC) was performed on representative whole tissue sections of a large retrospective cohort of de novo AS, RAAS, Stewart-Treves syndrome, and AVL and evaluated using a semi-quantitative scoring method. MYC is strongly expressed in the majority of RAAS and Stewart-Treves syndrome. De novo AS demonstrate variable MYC expression, with high-grade tumours showing significantly higher MYC expression than low-grade tumours. In contrast, MYC expression in AVL is predominantly negative but may occasionally show focal staining. These results indicate that unequivocal strong MYC IHC staining supports the diagnosis of RAAS. In rare cases of RAAS without strong MYC expression, however, particularly relatively low-grade tumours for which the differential diagnosis includes AVL, the distinction between these lesions should be made on morphological grounds using previously established criteria (i.e., significant atypia, deep invasion, infiltrative growth, etc.). Increased MYC expression in high-grade de novo AS suggests that MYC overexpression may play a role in the pathogenesis of these tumours, and MYC IHC may be a prognostic and/or therapeutic biomarker in a subset of these tumours.

Morphologic Mimics of Invasive Lobular Carcinoma.

Invasive lobular carcinoma of the breast is a relatively common diagnosis. However, other carcinomatous as well as noncarcinomatous neoplasms, either primary or metastatic to the breast, may mimic invasive lobular carcinoma. As treatment may differ, establishing the correct diagnosis is paramount to providing the appropriate care for these patients. This review outlines important mimics of invasive lobular carcinoma and the key clinicopathologic and immunohistochemical features as well as additional studies helpful in establishing their diagnoses.

Histopathological features of molluscum contagiosum other than molluscum bodies.

AIMS: Classic histopathological features of molluscum contagiosum (MC) include a crateriform, acanthotic epidermis containing intracytoplasmic molluscum bodies (MBs). In our experience, a subset of cases lack these features on initial haematoxylin and eosin-stained sections. We aimed to describe the histopathological features of MC other than those classically described. METHODS AND RESULTS: Sixty-seven biopsies diagnosed as MC from January 2011 to October 2012 were retrospectively reviewed. Keratinocytes peripheral to the diagnostic cells with MBs had prominent nucleoli (67; 100%), amphophilic cytoplasm (54; 81%), and in many instances clear cytoplasmic vacuolization (38; 57%). Stroma surrounding MC lesions showed fibroedematous to fibromyxoid changes in many cases (36; 54%), with a subset (13; 19%) showing abundant dermal mucin. In eight of 67 cases (12%), initial sections did not possess MBs or crateriform epidermis of MC. In these cases, initial sections revealed only the epithelial and/or perilesional stromal changes described above. Additional sections contained MBs in all of these cases. CONCLUSIONS: Perilesional fibroedematous to fibromyxoid stroma and keratinocyte changes, including prominent nucleoli and amphophilic cytoplasm with clear vacuolization, are common in MC. Recognizing these features may prove helpful in reaching the diagnosis of MC in cases lacking classic histopathological features on initial sections.