Morphologic and immunophenotypic evidence of in-situ Kaposi's sarcoma

BACKGROUND: The spectrum of Kaposi's sarcoma (KS) has been expanded to include pre-KS lesions. CASE PRESENTATION: We report, for the first time, a case providing direct histological evidence of the development of early (in-situ) KS from mediastinal lymphatic vessels in the setting of chronic lymphedema in an HIV-positive patient. Spindle-shaped and endothelial cells in these early KS-appearing lesions were immunoreactive for HHV8, D2-40 and CD34. CONCLUSION: Our findings suggest that HHV8-infected spindle-shaped cells associated with lymphangiogenesis that evolve into KS lesions, acquire from the outset an aberrant mixed vascular and lymphatic endothelial cell phenotype

A Preliminary Investigation into Search and Matching for Tumour Discrimination in WHO Breast Taxonomy Using Deep Networks

Breast cancer is one of the most common cancers affecting women worldwide. They include a group of malignant neoplasms with a variety of biological, clinical, and histopathological characteristics. There are more than 35 different histological forms of breast lesions that can be classified and diagnosed histologically according to cell morphology, growth, and architecture patterns. Recently, deep learning, in the field of artificial intelligence, has drawn a lot of attention for the computerized representation of medical images. Searchable digital atlases can provide pathologists with patch matching tools allowing them to search among evidently diagnosed and treated archival cases, a technology that may be regarded as computational second opinion. In this study, we indexed and analyzed the WHO breast taxonomy (Classification of Tumours 5th Ed.) spanning 35 tumour types. We visualized all tumour types using deep features extracted from a state-of-the-art deep learning model, pre-trained on millions of diagnostic histopathology images from the TCGA repository. Furthermore, we test the concept of a digital "atlas" as a reference for search and matching with rare test cases. The patch similarity search within the WHO breast taxonomy data reached over 88% accuracy when validating through "majority vote" and more than 91% accuracy when validating using top-n tumour types. These results show for the first time that complex relationships among common and rare breast lesions can be investigated using an indexed digital archive

PD-L1 in oral squamous cell carcinoma: A key biomarker from the laboratory to the bedside

Objectives and background: Oral squamous cell carcinoma (OSCC) is a highly malignant disease with an increasing incidence. The need to improve therapeutic strategies for patients affected by OSCC is an urgent challenge. Currently, the advent of immunotherapy represents an important step toward this aim. Programmed cell death-ligand 1 (PD-L1), a membrane protein that can be expressed on tumor and inflammatory cells is a key biomarker whose expression is determined by means of immunohistochemistry and is necessary for selecting patients for immunotherapy. Methods: In this study, we review the methods of PD-L1 assessment and outcomes achieved with immunotherapy in the treatment of OSCC patients. Results: Based on a meta-analysis we demonstrate a lack of prognostic significance of PD-L1 in OSCC. Conclusions: We also highlight unresolved issues including difficulties in standardizing PD-L1 evaluation and discuss future opportunities such as leveraging digital pathology

Primary breast lymphoma: a consideration in an HIV patient when a mass is discovered by screening mammography: a case report

Primary Breast lymphoma is a rare lesion that has been reported in patients without HIV. However, Primary Breast lymphoma occurring in a patient with HIV has rarely been reported despite the fact that HIV infection is known to increase the propensity to develop certain types of lymphoma. We report a case of an HIV patient with breast lymphoma that was discovered by screening mammography while presenting our argument for more cautionary management in this patient population

Crohn\u27s disease-associated ATG16L1 T300A genotype is associated with improved survival in gastric cancer

BACKGROUND: A non-synonymous single nucleotide polymorphism of the ATG16L1 gene, T300A, is a major Crohn\u27s disease (CD) susceptibility allele, and is known to be associated with increased apoptosis induction in the small intestinal crypt base in CD subjects and mouse models. We hypothesized that ATG16L1 T300A genotype also correlates with increased tumor apoptosis and therefore could lead to superior clinical outcome in cancer subjects. METHODS: T300A genotyping by Taqman assay was performed for gastric carcinoma subjects who underwent resection from two academic medical centers. Transcriptomic analysis was performed by RNA-seq on formalin-fixed paraffin-embedded cancerous tissue. Tumor apoptosis and autophagy were determined by cleaved caspase-3 and p62 immunohistochemistry, respectively. The subjects\u27 genotypes were correlated with demographics, various histopathologic features, transcriptome, and clinical outcome. FINDINGS: Of the 220 genotyped subjects, 163 (74%) subjects carried the T300A allele(s), including 55 (25%) homozygous and 108 (49%) heterozygous subjects. The T300A/T300A subjects had superior overall survival than the other groups. Their tumors were associated with increased CD-like lymphoid aggregates and increased tumor apoptosis without concurrent increase in tumor mitosis or defective autophagy. Transcriptomic analysis showed upregulation of WNT/β-catenin signaling and downregulation of PPAR, EGFR, and inflammatory chemokine pathways in tumors of T300A/T300A subjects. INTERPRETATION: Gastric carcinoma of subjects with the T300A/T300A genotype is associated with repressed EGFR and PPAR pathways, increased tumor apoptosis, and improved overall survival. Genotyping gastric cancer subjects may provide additional insight for clinical stratification

Gallium scintigraphy in the diagnosis and total lymphoid irradiation of Takayasu's arteritis

Takayasu's arteritis (TA) in children causes appreciable morbidity and mortality, predominantly as a result of the complication of renovascular hypertension (RVH). Ten children with TA, complicated by RVH, were treated at our centre over the past decade. An initial raised erythrocyte sedimentation rate (ESR) and a purified protein derivative greater than 15 mm were present in every case. More recently, gallium scintigraphy has been used to demonstrate sites of active inflammation in affected vessels (3/4 patients) which became negative after total lymphoid irradiation (TU). The latter was used in the last 6 children, and appeared to be effective in controlling disease activity as evinced in the normalisation of their ESRs and negative findings on gallium scintigraphy (in all 3 patients with prior active inflammation). Because of vascular damage caused by the vasculitic process, surgical intervention is often required to improve organ perfusion, particularly of the kidney/so Renal autografting (or allografting) seems preferable (6/11 kidneys functional) to renal bypass grafting (5/5 kidneys clotted). Patient survival improved when TU was used in addition to standard surgical and medical therapy; this included steroids and antituberculous therapy with TU, and steroids and cyclophosphamide in the two relapses. Five of 6 patients treated with TU were alive after 32 - 54 months' follow-up, while 4 patients who received standard medical and surgical therapy but not TU all died within 18 months of diagnosis. Gallium scintigraphy is a helpful diagnostic tool in assessing vasculitic activity in TA; TU is an important mode of immunosuppression, but still needs to be compared with cyclophosphamide as the major immunosuppressive

HIV-associated bladder cancer: a case series evaluating difficulties in diagnosis and management

<p>Abstract</p> <p>Background</p> <p>Chronic human immunodeficiency virus (HIV) infection is associated with an increased incidence of Non-Acquired Immunodeficiency Syndrome (non-AIDS) defining cancers. To date, only a limited number of cases of bladder cancer have been linked with HIV infection. We sought to describe the clinical characteristics of HIV-associated bladder cancer.</p> <p>Methods</p> <p>A retrospective study was performed involving HIV-positive patients with bladder cancer, combining cases from multiple institutions with published case reports. Data regarding patient demographics, HIV status, clinical presentation, pathology, cancer treatment, and outcome were analyzed using descriptive statistics.</p> <p>Results</p> <p>Eleven patients were identified with a median age of 55 years (range, 33 - 67). The median CD4+ count at cancer diagnosis was 280 cells/mm³(range, 106 - 572 cells/mm³). Six patients (55%) had a known risk factor for bladder cancer, and nine (82%) presented with hematuria. Ten patients had transitional cell carcinoma, and most had superficial disease at presentation. Treatment included mainly transurethral resection of bladder tumor followed by a combination of local and systemic therapies. One patient received intravesical bacillus Calmette-Guèrin (BCG) without complication. Several patients (55%) were alive following therapy, although many (64%) suffered from local relapse and metastatic disease.</p> <p>Conclusion</p> <p>Bladder cancer is part of the growing list of cancers that may be encountered in patients living longer with chronic HIV-infection. Our patients presented at a younger age and with only mild immunosuppression, however, they experienced an expected course for their bladder cancer. Hematuria in an HIV-infected patient warrants a complete evaluation.</p

Extramedullary myeloma in an HIV-seropositive subject. Literature review and report of an unusual case

Myeloma is characterized by monoclonal bone marrow plasmacytosis, the presence of M-protein in serum and/or in urine and osteolytic bone lesions. HIV-seropositive subjects with myeloma are younger at the time of diagnosis of the tumour and usually the myeloma has a more aggressive clinical course than it does in HIV-seronegative subjects

Cancers in the TREAT Asia HIV Observational Database (TAHOD): a retrospective analysis of risk factors

<p>Abstract</p> <p>Background</p> <p>This retrospective survey describes types of cancers diagnosed in HIV-infected subjects in Asia, and assesses risk factors for cancer in HIV-infected subjects using contemporaneous HIV-infected controls without cancer.</p> <p>Methods</p> <p>TREAT Asia HIV Observational Database (TAHOD) sites retrospectively reviewed clinic medical records to determine cancer diagnoses since 2000. For each diagnosis, the following data were recorded: date, type, stage, method of diagnosis, demographic data, medical history, and HIV-related information. For risk factor analyses, two HIV-infected control subjects without cancer diagnoses were also selected. Cancers were grouped as AIDS-defining cancers (ADCs), and non-ADCs. Non-ADCs were further categorized as being infection related (NADC-IR) and unrelated (NADC-IUR).</p> <p>Results</p> <p>A total of 617 patients were included in this study: 215 cancer cases and 402 controls from 13 sites. The majority of cancer cases were male (71%). The mean age (SD) for cases was 39 (10.6), 46 (11.5) and 44 (13.7) for ADCs, NADC-IURs and NADCs-IR, respectively. The majority (66%) of cancers were ADCs (16% Kaposi sarcoma, 40% non-Hodgkin's lymphoma, and 9% cervical cancer). The most common NADCs were lung (6%), breast (5%) and hepatocellular carcinoma and Hodgkin's lymphoma (2% each). There were also three (1.4%) cases of leiomyosarcoma reported in this study. In multivariate analyses, individuals with CD4 counts above 200 cells/mm³were approximately 80% less likely to be diagnosed with an ADC (p < 0.001). Older age (OR: 1.39, p = 0.001) and currently not receiving antiretroviral treatment (OR: 0.29, p = 0.006) were independent predictors of NADCs overall, and similarly for NADCs-IUR. Lower CD4 cell count and higher CDC stage (p = 0.041) were the only independent predictors of NADCs-IR.</p> <p>Conclusions</p> <p>The spectrum of cancer diagnoses in the Asia region currently does not appear dissimilar to that observed in non-Asian HIV populations. One interesting finding was the cases of leiomyosarcoma, a smooth-muscle tumour, usually seen in children and young adults with AIDS, yet overall quite rare. Further detailed studies are required to better describe the range of cancers in this region, and to help guide the development of screening programmes.</p