Childhood sarcoidosis: A rare but fascinating disorder

Childhood sarcoidosis is a rare multisystemic granulomatous disorder of unknown etiology. In the pediatric series reported from the southeastern United States, sarcoidosis had a higher incidence among African Americans. Most reported childhood cases have occurred in patients aged 13–15 years. Macrophages bearing an increased expression of major histocompatibility class (MHC) II molecules most likely initiate the inflammatory response of sarcoidosis by presenting an unidentified antigen to CD4+ Th (helper-inducer) lymphocytes. A persistent, poorly degradable antigen driven cell-mediated immune response leads to a cytokine cascade, to granuloma formation, and eventually to fibrosis. Frequently observed immunologic features include depression of cutaneous delayed-type hypersensitivity and a heightened helper T cell type 1 (Th1) immune response at sites of disease. Circulating immune complexes, along with signs of B cell hyperactivity, may also be found. The clinical presentation can vary greatly depending upon the organs involved and age of the patient. Two distinct forms of sarcoidosis exist in children. Older children usually present with a multisystem disease similar to the adult manifestations, with frequent hilar lymphadenopathy and pulmonary infiltrations. Early-onset sarcoidosis is a unique form of the disease characterized by the triad of rash, uveitis, and arthritis in children presenting before four years of age. The diagnosis of sarcoidosis is confirmed by demonstrating a typical noncaseating granuloma on a biopsy specimen. Other granulmatous diseases should be reasonably excluded. The current therapy of choice for sarcoidosis in children with multisystem involvement is oral corticosteroids. Methotrexate given orally in low doses has been effective, safe and steroid sparing in some patients. Alternative immunosuppressive agents, such as azathioprine, cyclophosphamide, chlorambucil, and cyclosporine, have been tried in adult cases of sarcoidosis with questionable efficacy. The high toxicity profile of these agents, including an increased risk of lymphoproliferative disorders and carcinomas, has limited their use to patients with severe disease refractory to other agents. Successful steroid sparing treatment with mycophenolate mofetil was described in an adolescent with renal-limited sarcoidosis complicated by renal failure. Novel treatment strategies for sarcoidosis have been developed including the use of TNF-alpha inhibitors, such as infliximab. The long-term course and prognosis is not well established in childhood sarcoidosis, but it appears to be poorer in early-onset disease

Immunomodulatory Therapy in Head and Neck Squamous Cell Carcinoma: Recent Advances and Clinical Prospects

The immune system plays a significant role in the development, invasion, progression, and metastasis of head and neck cancer. Over the last decade, the emergence of immunotherapy has irreversibly altered the paradigm of cancer treatment. The current treatment modalities for head and neck squamous cell carcinoma (HNSCC) include surgery, radiotherapy, and adjuvant or neoadjuvant chemotherapy which has failed to provide satisfactory clinical outcomes. To encounter this, there is a need for a novel or targeted therapy such as immunological targets along with conventional treatment strategy for optimal therapeutic outcomes. The immune system can contribute to promoting metastasis, angiogenesis, and growth by exploiting the tumor's influence on the microenvironment. Immunological targets have been found effective in recent clinical studies and have shown promising results. This review outlines the important immunological targets and the medications acting on them that have already been explored, are currently under clinical trials and are further being targeted. </jats:p

A Multi- institutional Prospective Analysis of Impact of CanAssist Breast (Morphometric Immunohistochemistry Based Test) on Adjuvant Chemotherapy Decisions in Early Breast Cancer

Abstract Purpose: CanAssist Breast (CAB) has been validated retrospectively for assessing risk of recurrence and thereby usefulness of chemotherapy in HR+/HER2- breast cancer. The objective of this study is to assess the agreement between physician’s treatment plan and CAB risk stratification and evaluate whether CAB results aid in the physician’s treatment decision.Methods: The data on the physician’s treatment plan before and after the CAB test was collected prospectively between 2016 and 2021 in 249 patients. Changes in treatment recommendations and compliance with CAB reports were analyzed. Results: Based on conventional clinicopathological features physicians planned to treat 46% of patients with endocrine therapy (ET) (low-risk-LR)), 24% with chemoendocrine therapy (CET) (high-risk-HR)) and in 30% physicians were uncertain of prescribing chemotherapy (intermediate-risk-IR)) before CAB testing. The correlation between clinical risk assessment and CAB risk stratification (k=0.2 (0.05-0.35) was nonsignificant. CAB classified 64% as LR, which was 18% (9.3-25, P=0.0001) higher compared to clinical LR. In the clinical IR category, CAB risk proportions were 55:45 (LR: HR). We observed a substantial shift in treatment recommendation from CET to ET in 54% (40.75- 66.84, P&lt;0.0001) of clinical HR and ET to CET in 26% (18.27- 35.01, P&lt;0.0001) of clinical LR patients. Overall CAB lead to change in treatment recommendation in 42% of the cohort.Conclusions: There was a significant impact of CAB on the physician’s treatment decision. CAB provided definite treatment recommendation to IR patients where the physician had dilemma on prescribing chemotherapy and provided precise treatment plan to clinical LR and HR patients.</jats:p