Analysis of Histopathological Findings of Lung Carcinoma in Czech Black Coal Miners in Association with Coal Workers’ Pneumoconiosis

Coal miners with coal workers’ pneumoconiosis (CWP, J60 according to ICD-10) were previously found to have a significantly higher risk of lung carcinoma compared to the general male population. The presented study aimed to analyze the (i) incidence of lung carcinoma in miners, (ii) histopathological findings in cohorts with and without CWP, and (iii) effect of smoking cessation on the histopathological profile. Analyzed cohorts consisted of miners with (n = 3476) and without (n = 6687) CWP. Data on personal and working history obtained from the medical records were combined with information on lung cancer from the Czech Oncological Register and histopathological findings. Statistical analysis was performed using non-parametric tests and the incidence risk ratio at the significance level of 5%. In 1992–2015, 180 miners (2.7%) without CWP and 169 (4.9%) with CWP, respectively, were diagnosed with lung carcinoma. The risk of lung cancer in miners with CWP was 1.82 (95% CI: 1.48–2.25) times higher than in those without CWP. Squamous cell carcinoma (37%) was the most common histopathological type, followed by adenocarcinoma (22%) and small cell carcinoma (21%). A statistically significant difference between the cohorts (p = 0.003) was found in the histopathological subtypes, with the incidence of small cell carcinoma being 2 times higher in miners without CWP than in those with CWP. Only a few individuals with lung carcinoma were non-smokers. The incidence of small cell carcinoma, which is strongly associated with smoking, is significantly higher in miners without CWP. Smoking constitutes the most important risk factor for developing lung carcinoma even in that cohort. However, CWP remains a very important risk factor.

Concurrent Paraneoplastic Dermatomyositis and Acquired C1 Esterase Inhibitor Deficiency in Primary Laryngeal Small Cell Carcinoma

Small cell carcinoma is associated with a number of paraneoplastic syndromes. We report a case of a 42-year-old female who presented with primary laryngeal small cell carcinoma associated with concurrent paraneoplastic dermatomyositis and paraneoplastic angioedema secondary to acquired C1 esterase inhibitor deficiency. The patient required extensive treatment for her dermatomyositis including high-dose corticosteroid therapy and intravenous immunoglobulin followed by steroid-sparing disease-modifying immunosuppression. Her angioedema also required multiple lines of therapy including bradykinin inhibitors and human recombinant C1 esterase. We believe this is the first reported case of either of these paraneoplastic syndromes arising from an extrapulmonary small cell carcinoma and highlights the difficulty of its initial diagnosis as well as concurrent management.

Malignant Melanoma With Neuroendocrine Differentiation: A Case Report and Literature Review

BackgroundMelanoma has a wide range of histologic variants and cytomorphologic features that make its diagnosis challenging. Melanoma can also rarely have neuroendocrine markers adding further diagnostic uncertainty particularly given that unrelated tumor types, such as prostate cancer, can also display focal neuroendocrine differentiations.Case presentationOur patient is a 74-year-old Caucasian man found to have a lung mass. Initial biopsy revealed typical microscopic morphology and neuroendocrine differentiation consistent with small cell carcinoma. Despite standard chemoradiation treatment, the patient continued to progress with new metastasis in the brain, liver and bone. Subsequent chest wall biopsy revealed golden-brown pigment associated with melanin. Further tumor immunohistochemistry revealed extensive neuroendocrine differentiation with CD56, synaptophysin, and INSM1, as well as strong immunoreactivity for melanocyte markers including SOX10, S100, PRAME, and MITF, consistent with metastatic melanoma with neuroendocrine differentiation. Genomic testing revealed increased tumor mutational burden and alterations in NF1, BRAF, CDKN2A/B, TERT. The patient was transitioned to checkpoint inhibitor therapy with nivolumab and ipilimumab and had resolution of his intracranial mass and decrease in size of other metastatic lesions.ConclusionOften the combination of anatomic findings such as a lung mass, typical microscopic morphology, and confirmation of neuroendocrine differentiation correctly identifies a patient with small cell carcinoma. However, in a patient who fails to respond to treatment, a broader immunohistochemical workup along with molecular testing with additional tissue may be warranted.

The opposing action of stromal cell proenkephalin and stem cell transcription factors in prostate cancer differentiation

Background Loss of prostate cancer differentiation or de-differentiation leads to an untreatable disease. Patient survival would benefit if this can be prevented or reversed. Cancer de-differentiation transforms luminal-like (differentiated) adenocarcinoma into less luminal-like and more stem-like (undifferentiated) small cell carcinoma through a sequential activation of stem cell transcription factors (scTF) POU5F1, LIN28A, SOX2 and NANOG. Like stem cells, prostate small cell carcinoma express this quartet of scTF as well as a 10-fold lower level of β2-microglobulin (B2M) than that of differentiated cell types. In organ development, prostate stromal mesenchyme cells mediate epithelial differentiation in part by secreted factors. Methods The identified prostate stromal-specific factor proenkephalin (PENK) was cloned, and transfected into scTF+B2Mlo stem-like small cell carcinoma LuCaP 145.1, reprogrammed luminal-like scTF−B2Mhi LNCaP, and luminal-like scTF−B2Mhi adenocarcinoma LuCaP 70CR. The expression of scTF, B2M and anterior gradient 2 (AGR2) was analyzed in the transfected cells. Results PENK caused down-regulation of scTF and up-regulation of B2M to indicate differentiation. When transfected into reprogrammed LNCaP, PENK reversed the reprogramming by down-regulation of scTF with attendant changes in cell appearance and colony morphology. When transfected into LuCaP 70CR, PENK up-regulated the expression of adenocarcinoma antigen AGR2, a marker associated with cancer cell differentiation. Conclusions Prostate cancer cells appear to retain their responsiveness to stromal PENK signaling. PENK can induce differentiation to counter de-differentiation caused by scTF activation. The many mutations and aneuploidy characteristic of cancer cells appear not to hinder these two processes. Loss of prostate cancer differentiation is like reprogramming from luminal-like to stem-like.

Symptom clusters among the patients with carcinoma lung attending palliative care department: a retrospective analysis

Background: There is growing interest in the symptom cluster of these symptoms rather than single symptoms and has been commonly termed as respiratory distress cluster. So, we conducted this audit review with a goal to explore the prevalence of RDS among lung cancer patients and to find association between RDS and the histological type of lung cancer.Methods: A retrospective review of records of lung cancer patients referred to palliative care department at Tata medical center, Kolkata, India was done. The records of 6 months (July 2018 to December 2018) were reviewed and relevant details were noted down. Hospital management system of our institution was screened for all the lung cancer patients during the above said period. Demographic details and various symptoms like cough, breathlessness, fatigue and other symptoms were also noted. Histological diagnosis was also noted as per the records. Results: We found that 20.24% had cough with fatigue, 20.24% had cough with breathlessness, 25% had fatigue with breathlessness and 13.10% had cough, fatigue and breathlessness in the present study. The proportion of fatigue was significantly higher among the small cell type (75%) when compared to non small cell type (p=0.0425) The proportion of SxCl cough with fatigue was significantly higher among the small cell carcinoma (60%) when compared to other subtypes. (p=0.0467)Conclusions: Among symptom clusters, fatigue with breathlessness was the most common. The proportion of fatigue and fatigue with cough was significantly higher among small cell carcinomas when compared to non small cell carcinoma subtype.