The mechanism by which the virus associated with dengue fever can cause a fatal hepatitis is not well understood. The purpose of this study was to examine 9 cases of fatal dengue hemorrhagic fever-associated hepatitis, and to correlate the histologic findings with viral detection and cytokine response. The histologic changes were nonspecific and included massive hepatic necrosis and a pauci-cellular acute hepatitis. Viral cDNA detection by reverse transcriptase in situ polymerase chain reaction demonstrated that the fatal hepatitis was due to infection on average of >90% of hepatocytes and many Kupffer cells. Similar results were obtained using immunohistochemistry for viral protein using an automated highly sensitive system. Immunohistochemical analysis for tumor necrosis factor alpha, and interleukin-2, showed rare positive Kupffer cells. In comparison, fatal cases of hepatitis C associated liver failure demonstrated far fewer infected hepatocytes and a concomitant strong up-regulation of many cytokines, notably tumor necrosis factor alpha and interleukin-2. It is concluded that fatal dengue hemorrhagic fever is associated with acute, severe liver damage due primarily to massive direct infection of hepatocytes and Kupffer cells with minimal cytokine response. The infection can be readily detected in a few hours using an automated system that has a sensitivity equivalent to reverse transcriptase in situ polymerase chain reaction.

Dirofilaria immitis is the causative agent of canine heartworm, a well known parasitic cardiopulmonary disease of dogs and cats, that can also affect man (NB Robinson et al. 1977 J Thor Cardiov Surg 74: 403-408). When this nematode infects man the disease is difficult to diagnose, but even so there are more than 200 cases of human pulmonary dirofilariasis reported throughout the world (

Clear cell acanthoma is an uncommon type of benign epithelial tumor. Typically, it is a solitary lesion found on the lower limbs. It presents as a nodule or small plaque with slow and well-defined growth. Diagnosis used to be clinical and histopathological, but the advent of dermoscopy has led to an increase in diagnostic accuracy. We describe a case in which dermoscopy proved highly useful for diagnosis of the lesion.

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The histologic features of cervical intraepithelial neoplasia (CIN 1), caused by infection by the human papillomavirus (HPV), can overlap with those of its mimics that can lead to an over diagnosis of this sexually transmitted disease. In this study, 67 consecutive cervical biopsies that were diagnosed as CIN 1 from the surgical files of Ohio State University Medical Center were analyzed. Twenty controls (10 CIN 1 cervical biopsies and 10 normal cervical tissues) were also studied. The 87 biopsies were reevaluated blinded to the original diagnosis and the results were correlated with detection of HPV DNA by in situ hybridization and glycogen by the periodic acid solution (PAS)/PAS-D stain, respectively. HPV was detected by in situ hybridization in 55/67 cases (82%); no virus was evident in the negative controls whereas each of the 10 CIN 1 controls was virus positive. A PAS test demonstrated in the mature squamous component of the negative controls a strong signal in cells with prominent and uniform halos, which was lost with diastase treatment, indicative of abundant glycogen. The PAS/PAS-D tests in the CIN 1 lesions showed rare variable sized glycogen deposits in the dysplastic cells. Nine (15%) cases initially diagnosed as CIN 1 were HPV negative by in situ hybridization and had halolike cells that were strongly and uniformly positive for glycogen. This data underscores the value of glycogen and HPV analyses in improving the specificity of the diagnosis of CIN 1.

Immunotherapies provide long-lasting responses across a wide range of cancers; however, only a fraction of patients responds to them. Multiple reasons contribute to the failure, including the existence of myeloid-derived cells (MDCs) within tumors. Due to their high plasticity, these cells display numerous cell states and, as a result, distinct pro-tumorigenic behaviors, making them interesting targets. However, the creation of cutting-edge anticancer therapies is hampered by the lack of MDC-specific markers. To fully define the MDC landscape in solid tumors, we combined single-cell RNA-Seq from 13 public datasets, including samples from seven different cancers and normal samples, yielding the largest collection of MDC subpopulations within the tumor microenvironment. We identified five major lineages subdivided into one mast cell cluster, three neutrophils, eight dendritic cells, six monocytes, and eleven macrophage states. Transcriptional profiles coupled with deconvolution estimates of cell populations in large cohorts revealed five MDC subpopulations as independent prognostic markers in different cancer types, including resident tissue interstitial macrophages and FCGR3A+ monocytes associated with an unfavorable clinical outcome in ovarian and breast cancer patients, respectively. Our work reveals that TREM2+ macrophages can be distinguished in different populations and associated with distinct prognoses. By analyzing a Brazilian cohort of ovarian cancer, we found that TREM2+ macrophages are associated with a better prognosis, indicating that their role might be dependent on the tumor niche and co-expression of immunosuppressive markers. Collectively, this atlas reveals in high-resolution the heterogeneous MDC identity as well as new avenues for understanding and manipulating their fate in cancer.