Paraneoplastic secretion of multiple phosphatonins from a deep fibrous histiocytoma causing oncogenic osteomalacia

Context: Literature suggests that oncogenic osteomalacia is usually caused by a benign mesenchymal tumor secreting fibroblast growth factor subtype-23 (FGF-23), but the involvement of other phosphatonins has only been scarcely reported. We have previously published a seemingly typical case of oncogenic osteomalacia. Following curative neoplasm resection, we now report unique molecular characteristics and biology of this tumor. Case Description: A 25-year-old man had been diagnosed with severe oncogenic osteomalacia that gradually crippled him over 6 years. 68Ga-DOTA-TATE positron emission tomography/computed tomography scan localized the culprit tumor to his left sole, which on resection revealed a deep fibrous histiocytoma displaying a proliferation of spindle cells with storiform pattern associated with multinucleated giant cells resembling osteoclasts. Circulating FGF-23, which was elevated more than 2-fold, declined to undetectable levels 24 h after surgery. Microarray analysis revealed increased tumor gene expression of the phosphatonins FGF-23, matrix extracellular phosphoglycoprotein (MEPE) and secreted frizzled-related protein subtype 4, with elevated levels of all 3 proteins confirmed through immunoblot analysis. Differential expression of genes involved in bone formation and bone mineralization were further identified. The patient made an astonishing recovery from being wheelchair bound to fully self-ambulant 2 months postoperatively. Conclusion: This report describes oncogenic osteomalacia due to a deep fibrous histiocytoma, which coincidentally has been found to induce profound muscle weakness via the overexpression of 3 phosphatonins, which resolved fully upon radical resection of the tumor. Additionally, genes involved in bone formation and bone remodeling contribute to the molecular signature of oncogenic osteomalacia

Clinics in diagnostic imaging (212)

A 75-year-old woman presented in 2014 with a non-resolving left lower lobe consolidation. Initial less invasive attempts at biopsy of the left lower lobe consolidation failed to obtain a definitive diagnosis, and the patient underwent a left lower lobectomy and lymph node dissection. Histology revealed adenocarcinoma with no lymphovascular invasion, and she was diagnosed with Stage IIA lung adenocarcinoma. She did not require radiotherapy and declined adjuvant chemotherapy. Upper lung changes on initial preoperative computed tomography (CT) of the thorax performed in 2014 (Fig. 1) were originally interpreted to be due to benign post-infectious scarring. The patient subsequently underwent surveillance CT of the thorax over a period of time until 2020. She had no chronic cough, sputum production or worsening exertional dyspnoea over the years. She was a non-smoker and her body mass index (BMI) was 12.6 kg/m2 on her latest review. Her oxygen saturation was 98% on room air, and physical examination revealed reduced breath sounds over the left lung, with bilateral fine crepitations. There were no signs suggestive of a connective tissue disease. An autoimmune screen comprising anti-nuclear antibody, rheumatoid factor and anti-cyclic citrullinated peptide tests was negative, and the patient was unable to produce sputum to screen for acid-fast bacilli. She held multiple jobs previously, including dishwashing, cleaning and being a kitchen helper. What do the initial CT done in 2014 (Fig. 1) and subsequent CT done in 2019 (Fig. 2) show? What is the diagnosis

Malignant Transformation of Heterotopic Pancreatic Tissue in a Patient with BRCA2 Mutation

Background: Malignant transformation of heterotopic pancreatic tissue is a rare entity with only several case reports published in the scientific literature. Adjuvant chemotherapy following oncological resection for lesions with nodal metastasis has not been well described and there are no guidelines available to guide the management of these patients. Case Presentation: We present a case of gastric heterotopic pancreatic carcinoma with nodal metastasis in a young patient with breast cancer gene (BRCA) 2 mutation. He had undergone a laparoscopic wedge resection for a gastric lesion initially thought to be a gastrointestinal stroma tumor. Given the involvement of the wedge resection margins, the patient underwent a distal gastrectomy with oncological lymph nodal clearance. One out of the 33 harvested lymph nodes harboured micrometastasis while the main gastrectomy specimen did not have any residual malignancy. Following the histological diagnosis, he received an adjuvant chemotherapy regime akin to that prescribed for locally advanced pancreatic adenocarcinoma with good response. This is, to our knowledge, also the first such case report in a patient with BRCA2 mutation. Conclusions: Pre-operative diagnostic confirmation is challenging and endoscopic procedures pose significant false negatives. Reports of nodal metastasis following oncological resection are limited and there are no guidelines regarding adjuvant therapies. We would recommend a chemotherapy regimen similar to that for primary locally advanced pancreatic carcinoma in patients found to have nodal metastasis

One Patient, Two Uncommon B-Cell Neoplasms: Solitary Plasmacytoma following Complete Remission from Intravascular Large B-Cell Lymphoma Involving Central Nervous System

Second lymphoid neoplasms are an uncommon but recognized feature of non-Hodgkin’s lymphomas, putatively arising secondary to common genetic or environmental risk factors. Previous limited evaluations of clonal relatedness between successive mature B-cell malignancies have yielded mixed results. We describe the case of a man with intravascular large B-cell lymphoma involving the central nervous system who went into clinical remission following immunochemotherapy and brain radiation, only to relapse 2 years later with a plasmacytoma of bone causing cauda equina syndrome. The plasmacytoma stained strongly for the cell cycle regulator cyclin D1 on immunohistochemistry, while the original intravascular large cell lymphoma was negative, a disparity providing no support for clonal identity between the 2 neoplasms. Continued efforts atcataloging and evaluating unique associations of B-cell malignancies are critical to improving understanding of overarching disease biology in B-cell malignancies

Meat consumption and risk of lung cancer among never-smoking women

10.1080/01635581.2011.589961Nutrition and Cancer636850-859NUCA

Evidence for disease control with erlotinib after gefitinib failure in typical gefitinib-sensitive Asian patients with non-small cell lung cancer

10.1097/JTO.0b013e318168c801Journal of Thoracic Oncology34400-40