Nicotinamide for Skin-Cancer Chemoprevention in Transplant Recipients.

BACKGROUND: Immunosuppressed organ-transplant recipients have an increased incidence of, and mortality from, skin cancer. Nicotinamide (vitamin B3) enhances the repair of ultraviolet (UV) radiation-induced DNA damage, reduces the cutaneous immunosuppressive effects of UV radiation, and reduces the incidence of keratinocyte cancers (including squamous-cell and basal-cell carcinomas) and actinic keratoses among high-risk immunocompetent patients. Whether oral nicotinamide is useful for skin-cancer chemoprevention in organ-transplant recipients is unclear. METHODS: In this phase 3 trial, we randomly assigned, in a 1:1 ratio, organ-transplant recipients who had had at least two keratinocyte cancers in the past 5 years to receive 500 mg of nicotinamide or placebo twice daily for 12 months. Participants were examined for skin lesions by dermatologists at 3-month intervals for 12 months. The primary end point was the number of new keratinocyte cancers during the 12-month intervention period. Secondary end points included the numbers of squamous-cell and basal-cell carcinomas during the 12-month intervention period, the number of actinic keratoses until 6 months after randomization, safety, and quality of life. RESULTS: A total of 158 participants were enrolled, with 79 assigned to the nicotinamide group and 79 to the placebo group. The trial was stopped early owing to poor recruitment. At 12 months, there were 207 new keratinocyte cancers in the nicotinamide group and 210 in the placebo group (rate ratio, 1.0; 95% confidence interval, 0.8 to 1.3; P = 0.96). No significant between-group differences in squamous-cell and basal-cell carcinoma counts, actinic keratosis counts, or quality-of-life scores were observed. Adverse events and changes in blood or urine laboratory variables were similar in the two groups. CONCLUSIONS: In this 12-month, placebo-controlled trial, oral nicotinamide therapy did not lead to lower numbers of keratinocyte cancers or actinic keratoses in immunosuppressed solid-organ transplant recipients. (Funded by the National Health and Medical Research Council; ONTRANS Australian New Zealand Clinical Trials Registry number, ACTRN12617000599370.).

Mercaptopurine-induced Sweet's syndrome.

Sweet's syndrome is an acute febrile neutrophilic dermatosis. Drug-induced Sweet's syndrome typically occurs soon after drug administration, with rapid resolution of symptoms with cessation of the offending agent. We report a man in his early 40s who presented with fever and widespread erythematous rash on a background of recently diagnosed mild stricturing ileal Crohn's disease. He was commenced on 6-mercaptopurine 12 days before presentation. Skin biopsy demonstrated diffuse infiltration of neutrophils in the upper dermis, dermal oedema, eosinophils and fibrin deposition. Symptoms rapidly improved with cessation of 6-mercaptopurine without requiring systemic corticosteroids.

The hidden Australian skin cancer epidemic, high-risk cutaneous squamous cell carcinoma: a narrative review.

Deaths from non-melanoma skin cancers (NMSCs) have almost doubled in Australia in recent years. Cutaneous squamous cell carcinoma (cSCC) constitutes approximately 20% of NMSCs, but is responsible for most of the deaths. Most skin cancers are easy to diagnose and treat and therefore cSCC are often trivialised; however, there is a high-risk subgroup of cSCC (HRcSCC) that is associated with a high risk of metastasis and death. The definition of early HRcSCC and our ability to identify them is evolving. Many significant prognostic factors have been identified, but a universally accepted prognostic index does not exist. Guidelines for workup, treatment, and follow-up leave many important decisions open to broad interpretation by the treating physician or multidisciplinary team. Some of the treatments used for metastatic cSCC are not supported by robust evidence and the prognosis of metastatic cSCC is guarded. In this review, we highlight the rapid rise in NMSC deaths and discuss some of the deficiencies in our knowledge of how to define, diagnose, stage, and manage HRcSCC.

Management of basal cell carcinoma with pulmonary metastasis.

A man in his 50s presented with an ulcerative lesion within the left axillary fold that had progressively worsened over 18 months. Biopsy revealed an ulcerative basal cell carcinoma (BCC), which was surgically managed. CT chest scans done 7 months later assessed post-treatment of radiotherapy. This revealed pulmonary lesions, which were biopsy-proven metastatic BCC. Sonidegib, a hedgehog signalling inhibitor, was used for first-line treatment. Due to progressive disease, sonidegib was ceased. Cemiplimab, a checkpoint inhibitor, was used as second-line treatment based on a phase II trial demonstrating efficacy in the setting of metastatic BCC. CT reports were initially consistent with response but after 6 months of cemiplimab treatment, repeat CT chest scans revealed a decrease in size of the previously cited pulmonary lesions.This is a rare case of BCC metastases which has limited treatment options. This case provides insight of the patient experience on such treatment.

A mariner's tale: Invasive endotracheal Mycobacterium marinum infection.

Mycobacterium marinum is a ubiquitous water-borne non-tuberculous mycobacterial (NTM) pathogen. In humans, M. marinum infections are acquired through direct inoculation of skin wounds and are almost exclusively localized to skin and soft tissues. Pulmonary infection with M. marinum is extremely rare, and to our knowledge, invasive endobronchial disease has not been reported. Here, we present a case of a 71-year-old immunocompetent male surfer with invasive endotracheal M. marinum granulomatous disease. The patient was successfully cured with a regimen of azithromycin 250 mg daily, ethambutol 900 mg (15 mg/kg) daily and rifampicin 600 mg daily for 12 months following culture conversion. This case highlights several important concepts: Firstly, M. marinum infection, including invasive endobronchial infection, should be considered a rare cause of NTM pulmonary disease. Secondly, endotracheal infection can be successfully eradicated with this selected therapeutic regimen. Finally, the absence of M. marinum skin or soft-tissue infection in this patient, raises the possibility that human disease might also be acquired via inhalation of M. marinum contaminated water in rare circumstances.

A stonemason with accelerated silicosis in the setting of tumour necrosis factor alpha inhibitor therapy.

We present the case of a 26-year-old stonemason with accelerated silicosis in the setting of treatment for psoriasis with the tumour necrosis factor alpha (TNF-alpha) inhibitor adalimumab. Accelerated silicosis is an important occupational lung disease with a poor prognosis and limited treatment options [1]. Although the exact pathogenesis remains unknown, it is suggested that secretion of cytokines, including TNF-alpha, plays a central role in disease progression [1,2]. Importantly, however, TNF-alpha inhibitors, in addition to resulting in an increased risk of infection, are also now being seen to cause interstitial lung disease [3,4]. To our knowledge, this is the first documented patient to develop silicosis whilst on TNF-alpha inhibitor therapy. This case challenges the theory behind TNF-alpha's exact role in the pathogenesis of silicosis and lung fibrosis, highlights the importance of monitoring individuals with both occupational and drug exposures, and illustrates the increasing difficulties physicians face in investigating patients with pulmonary infiltrates and multiple possible aetiologies.

Use of microbubble contrast in the diagnosis of a left ventricular papillary fibroelastoma.

UNLABELLED: A papillary fibroelastoma is a rare, avascular, cardiac tumour that is often found incidentally using transthoracic echocardiography (TTE). Peripheral i.v. injection of a microbubble contrast agent is often used to characterize abnormal masses within the heart allowing further delineation of physical features, the area of attachment, and vascularity of the mass in order to differentiate the growth from a tumour or a thrombus. This case highlights a potential pitfall when assessing a cardiac tumour's vascularity using contrast TTE. A cardiac mass was identified on a TTE of a 53-year-old man and was further investigated with microbubble contrast-enhanced TTE. Contrast TTE imaging suggested a vascularized structure in the left ventricle. However, after histological examination the tumour was found to be entirely avascular. LEARNING POINTS: Differentiation of cardiac tumour is usually best performed with contrast echocardiography.Contrast echocardiography may not be best tool to determine if cardiac mass is vascularized.A papillary fibroelastoma can appear vascularized with contrast echocardiography due to it's frond-like structures.Physicians should be aware of this potential confusion when assessing a cardiac tumour in patients.

Mitosis trumps T stage and proposed international association for the study of lung cancer/american thoracic society/european respiratory society classification for prognostic value in resected stage 1 lung adenocarcinoma.

INTRODUCTION: We investigated whether a group of pathologists could reproducibly apply the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification for lung adenocarcinoma to a cohort of stage 1 tumors and whether this architectural classification and/or other parameters could demonstrate survival advantage. METHODS: A total of 145 cases of 7 edition of tumor, node, metastasis stage 1 adenocarcinoma were retrospectively reviewed for predominant architectural pattern, including cribriform pattern, nuclear grade, mitotic index, and necrosis. The parameters were assessed for reproducibility and survival and using multivariate analysis, compared with stage, age, and sex. RESULTS: The majority of tumors had a mixed architecture with the acinar pattern being the most common predominant architecture. Micropapillary and cribriform architecture were the least frequent patterns. This study demonstrated that a group of five pathologists could reproducibly apply the IASLC/ATS/ERS classification. Although there were insufficient cribriform-predominant adenocarcinomas for assessment, when the percentage of all cribriform was combined with other architectures, it was associated with a worse prognosis. The majority of the parameters assessed demonstrated significance with univariate analysis but only mitotic index, as assessed by the highest count/10 high-power fields remained significant with multivariate analysis. CONCLUSION: In this study of resected stage 1 primary lung adenocarcinoma, we found mitotic index to be the only independent prognostic marker. It was more closely associated with outcome than either pathologic T stage or IASLC/ATS/ERS architecture-based classification. Further validation of concordance and reproducibility in reporting mitotic index, as well as validation of prognostic significance, needs to be undertaken in independent data sets.

Diagnosis of granulocytic sarcoma on pleural effusion cytology: report of a case.

Granulocytic sarcoma is a rare manifestation of myeloid leukemia and is even rarer as a primary presentation. Granulocytic sarcoma may affect any organ and has many modes of presentation. Diagnosis by cytology is possible as long as the diagnosis is considered. Diagnosis by cytology of body cavity effusion fluid has rarely been described. We present an unusual case of granulocytic sarcoma in which pleural effusion was a part of the initial presentation. Cytologic examination of the pleural effusion was able to make the definitive diagnosis of granulocytic sarcoma.

Fine-needle aspiration diagnosis of sclerosing hemangioma (pneumocytoma): report of a case and review of the literature.

Sclerosing hemangioma (pneumocytoma) is a rare benign lung tumor with uncertain histogenesis but characteristic histology. Reports of the cytopathology of this tumor are even rarer with only a handful of cases in the literature--many of these incorrectly diagnosed by cytology initially. Herein, we describe a case of sclerosing hemangioma diagnosed prima facie by fine-needle aspiration cytology. A cell block preparation with accompanying immunohistochemistry was instrumental in making the diagnosis. A review of the literature is also presented.

A case of Castleman's disease and adult necrotizing aortitis: a co-incidence or a significance?

We report a case of concomitant Castleman's disease and adult necrotizing aortitis, an association heretofore not reported. A brief discussion of the current state of our understanding of the pathogenesis of aortitis and possible link between these two entities is presented.

Collagenous enterocolitis and maturity onset type 1 diabetes manifesting as uraemia, malabsorption and extreme weight loss.

A 37-year-old patient with type 1 diabetes had been recently diagnosed with collagenous colitis (CC) after sigmoidoscopy. She rapidly progressed from a fortnight of watery diarrhoea, to a malabsorptive state with severe dehydration and acute kidney injury. This necessitated admission to an intensive care unit for emergency dialysis. She was subsequently diagnosed with collagenous enterocolitis affecting gastric, small bowel and colonic mucosa which required systemic steroid therapy. Physicians caring for patients with CC should be aware of the potential extreme manifestations of upper gastrointestinal collagenous deposition.

National Working Group Meeting on ALK diagnostics in lung cancer.

The global landscape of molecular testing is rapidly changing, with the recent publication of the International Association for the Study of Lung Cancer (IASLC)/College of American Pathologists (CAP) guidelines and the ALK Atlas. The IASLC/CAP guidelines recommend that tumors from patients with non-small cell lung cancer (NSCLC) be tested for ALK rearrangements in addition to epidermal growth factor receptor (EGFR) mutations. The spur for this recommendation is the availability of novel therapies that target these rearrangements. This article is based on coverage of a Pfizer-sponsored National Working Group Meeting on ALK Diagnostics in Lung Cancer, held around the 15th World Lung Cancer Conference, in Sydney on October 31, 2013. It is based on the presentations given by the authors at the meeting and the discussion that ensued. The content for this article was discussed and agreed on by the authors.

Cardiac myxoma with oncocytic change--cardiac oncocytoma?

We report the case of an incidental cardiac myxoma that was remarkable for the presence of extensive oncocytic change, a feature that has not be reported previously. The oncocytes most likely represent part of a spectrum of degenerative changes present in the tumor, but the possibility that they are neoplastic is also discussed.

Right ventricular inflow tract obstruction secondary to metastatic cutaneous squamous cell carcinoma.

We report the case of an immunocompetent 83-year-old man with metastatic neoplastic infiltration of the heart from primary squamous cell carcinoma (SCC) of the skin. Death was from cardiopulmonary collapse due to left ventricular failure with features of right ventricular inflow tract obstruction. Metastatic tumours involving the heart rarely originate from cutaneous SCC though have been reported in the literature in both immunocompetent and postrenal-transplant recipient patients. Most involve the pericardium and only rarely the endocardium or the myocardium. While the prognosis is generally poor, palliative radiotherapy may provide significant symptom relief. Cardiac metastases should be considered in patients with advanced cancer, especially when they show cardiac symptoms and signs.