Nodular vasculitis associated with lung adenocarcinoma

Villin, cytokeratin 7, and cytokeratin 20 expression in pulmonary adenocarcinoma with ultrastructural evidence of microvilli with rootlets

Background Mycobacterium tuberculosis (MTB) infection has been suggested to contribute to the pathogenesis of erythema nodosum (EN) and nodular vasculitis (NV), the classic forms of panniculitis. However, there is little evidence to demonstrate the presence of MTB in the skin lesions. This study is aimed at evaluating the association between MTB infection and the development of EN and NV in a Chinese population.MethodsA total of 107 patients (36 EN, 27 NV, and 44 others) with vasculitis and 40 control cases with other skin diseases were recruited and their skin lesion samples were subjected to real time polymerase chain reaction (PCR) analysis of the IS6110 and mpt64 gene fragments of MTB. Their blood mononuclear cells were tested for MTB antigen-specific IFN-γ responses by QuantiFERON®-TB Gold In-Tube (IT) assays.ResultsPCR analysis revealed that 7/23 (30.4%) and 7/18 (38.9%) of the EN and NV samples were positive for the IS6110 DNA, respectively, which were significantly higher than 3/34 (8.8%) of other vasculitis (OV) and 3/40 (7.5%) of the control samples (p<0.05). The nested Real-Time PCR assay indicated that 6/7 (86%) of the IS6110-positive EN samples, all of the IS6110-positive NV and control samples, but only 1/3 of the IS6110-positive OV samples, were positive for the mpt64 gene. Similarly, 19/32 (59.4%) of the EN patients, 20/26 (76.9%) of the NV patients, and 17/36 (47.2%) of the OV patients were positive for MTB antigen-specific IFN-γ responses, which were significantly higher than 6/40 (15%) of the controls (p<0.05).ConclusionOur data strongly suggest that MTB infection and active TB are associated with the development of NV and EN in Chinese.

1200P - Exploring personalized immunotherapy opportunities in colorectal cancer

Erythema nodosum is the most common type of panniculitis; it may be due to a variety of underlying infectious or otherwise antigenic stimuli. The pathogenesis remains to be elucidated, but both neutrophilic inflammation and granulomatous inflammation are implicated. Beyond treating underlying triggers, therapeutic options consist mainly of nonsteroidal anti-inflammatory drugs, symptomatic care, potassium iodide, and colchicine. Erythema induratum (nodular vasculitis) is a related but distinctly different clinicopathologic reaction pattern of the subcutaneous fat. It is classically caused by an antigenic stimulus from Mycobacterium tuberculosis but may be associated with several other underlying disorders. After appropriate antimicrobial treatment in tuberculous cases, therapy for erythema induratum is similar to options for erythema nodosum.

To report a case of recurrent bilateral combined branch retinal vein occlusion (BRVO) and branch retinal artery occlusion (BRAO) with paracentral acute middle maculopathy (PAMM) as the first manifestation of lung adenocarcinoma. A 54-year-old male with a history of inferonasal BRVO in the left eye (LE), was referred to our department for blurred vision in the LE. On examination, best-corrected visual acuity was 20/20 in the right eye (RE) and 20/25 in the LE. Fundus examination showed tortuosity and dilatation of the inferotemporal branch vein, cotton-wool spots, retinal hemorrhages, and areas of retinal whitening in both eyes corresponding to a BRVO associated with BRAO and PAMM. A few months later, the patient complained of blurred vision in the RE. Examination revealed a superior temporal BRVO and BRAO. An exhaustive work-up was performed. Results showed a high level of antiphospholipid antibodies. Chest scan showed the presence of a pulmonary mass related to lung adenocarcinoma. The patient underwent a surgical removal of the lung tumoral mass and chemotherapy. The level of antiphospholipid antibodies was back to normal and no recurrence of ocular symptoms was noted after a follow-up of one year. The association between retinal vascular occlusions and systemic carcinomas is rare. Malignant tumors may induce a hypercoagulation state and an increased risk of thromboembolic complications including branch retinal vascular occlusions.

Cases of red fingers syndrome and nodular vasculitis in patients with hepatitis C have rarely been described. Both red fingers syndrome and nodular vasculitis are characterized by microscopic vasculitis, and it has been hypothesized that hepatitis C plays a role in the pathogenesis of cutaneous disorders such as vasculitis, especially in cryoglobulinaemic vasculitis. We describe the case of a 75-year-old woman diagnosed with chronic hepatitis C who presented with nodular lesions on her right thigh and red fingers syndrome. A skin biopsy taken from a nodule showed infiltration of the vessel walls by mononuclear cells and septal and lobular panniculitis. The diagnosis of nodular vasculitis was established. In our opinion, red fingers syndrome and nodular vasculitis might be related to a vascular reaction of immune-mediated mechanisms induced by hepatitis C.

Objective To determine whether a limited immunohistochemical panel can help differentiate metastatic colonic adenocarcinoma from primary enteric-type adenocarcinoma of the urinary tract and urothelial (transitional cell) carcinoma with glandular differentiation, which appear morphologically similar but most often necessitate different treatment protocols. Design We examined lower urinary tract tumors (5 urinary bladder, 2 urethral) from 7 patients with a history of colonic adenocarcinoma. The differential diagnoses in these cases included metastatic colonic adenocarcinoma, primary enteric-type adenocarcinoma of the urinary tract, and urothelial carcinoma with glandular differentiation. An immunohistochemical panel consisting of cytokeratin 7 (CK-7), cytokeratin 20 (CK-20), and villin was evaluated in all cases. Four primary enteric-type adenocarcinomas of the urinary tract and 5 conventional urothelial carcinomas were also studied to compare morphologic features and immunohistochemical staining patterns. Results Of the 7 cases, 6 were determined to be metastatic colonic adenocarcinoma and 1 was diagnosed as a primary urothelial carcinoma with glandular differentiation. All 6 metastatic colonic adenocarcinomas, 6 of the 7 primary colonic adenocarcinomas, and all 4 primary enteric-type adenocarcinomas of the urinary tract were CK-20 positive (1 was CK-20 negative), villin positive, and CK-7 negative. The single urothelial carcinoma with glandular differentiation and all 5 control cases of urothelial carcinoma were CK-7 and CK-20 positive, and villin negative. Conclusions We conclude that (1) villin is expressed in primary enteric-type adenocarcinoma of the urinary tract; (2) in difficult cases, urothelial carcinoma with glandular differentiation can be distinguished from colonic adenocarcinoma because the former is CK-7 positive, CK-20 positive, and villin negative, whereas the latter is CK-20 positive, villin positive, and CK-7 negative; (3) clinical information is essential when evaluating lower urinary tract tumors that are clinically and morphologically similar to enteric-type adenocarcinoma of the urinary tract; and (4) the similar immunohistochemical profiles of metastatic colonic adenocarcinoma and primary enteric-type adenocarcinoma of the urinary tract may be in keeping with the hypothesis that the latter arise from intestinal metaplasia.

To determine whether a limited immunohistochemical panel can help differentiate metastatic colonic adenocarcinoma from primary enteric-type adenocarcinoma of the urinary tract and urothelial (transitional cell) carcinoma with glandular differentiation, which appear morphologically similar but most often necessitate different treatment protocols. We examined lower urinary tract tumors (5 urinary bladder, 2 urethral) from 7 patients with a history of colonic adenocarcinoma. The differential diagnoses in these cases included metastatic colonic adenocarcinoma, primary enteric-type adenocarcinoma of the urinary tract, and urothelial carcinoma with glandular differentiation. An immunohistochemical panel consisting of cytokeratin 7 (CK-7), cytokeratin 20 (CK-20), and villin was evaluated in all cases. Four primary enteric-type adenocarcinomas of the urinary tract and 5 conventional urothelial carcinomas were also studied to compare morphologic features and immunohistochemical staining patterns. Of the 7 cases, 6 were determined to be metastatic colonic adenocarcinoma and 1 was diagnosed as a primary urothelial carcinoma with glandular differentiation. All 6 metastatic colonic adenocarcinomas, 6 of the 7 primary colonic adenocarcinomas, and all 4 primary enteric-type adenocarcinomas of the urinary tract were CK-20 positive (1 was CK-20 negative), villin positive, and CK-7 negative. The single urothelial carcinoma with glandular differentiation and all 5 control cases of urothelial carcinoma were CK-7 and CK-20 positive, and villin negative. We conclude that (1) villin is expressed in primary enteric-type adenocarcinoma of the urinary tract; (2) in difficult cases, urothelial carcinoma with glandular differentiation can be distinguished from colonic adenocarcinoma because the former is CK-7 positive, CK-20 positive, and villin negative, whereas the latter is CK-20 positive, villin positive, and CK-7 negative; (3) clinical information is essential when evaluating lower urinary tract tumors that are clinically and morphologically similar to enteric-type adenocarcinoma of the urinary tract; and (4) the similar immunohistochemical profiles of metastatic colonic adenocarcinoma and primary enteric-type adenocarcinoma of the urinary tract may be in keeping with the hypothesis that the latter arise from intestinal metaplasia.

Lung cancer with gastrointestinal metastasis is uncommon; however, when such metastasis occurs, the small bowel is the most common metastatic site. There are few case reports of colonic metastasis developing from a primary lung adenocarcinoma. We report a case of metastatic adenocarcinoma in the colon, complicated by bowel obstruction and hydropneumothorax, in a 67-year-old woman. The primary cancer was highly suspected to have originated from the lung, based on immunohistochemistry assessments. Immunohistochemistry was positive for thyroid transcription factor-1 and cytokeratin 7, but negative for cytokeratin 20. The published literature, focusing on the differential diagnosis of the origin of the primary malignancy using immunohistochemistry, was reviewed.

Erythema induratum (EI) is a rare chronic disease, which occurs with cutaneous tuberculosis (TB). Nodular vasculitis, much rarer than erythema induratum, describes the same condition but without cutaneous TB, with lesions usually in the lower legs and rarely on the breasts. We report the case of a 46-year-old female with a history of crusted skin and necrotic lesions two years before, which, once self-limited, multiplied one month before and transferred to uncommon sites of the body, such as the breast. There was no evidence of other clinical presentations, and a chest X-ray gave no pathological findings. A biopsy was taken from the lesions, and the patient was diagnosed with erythema induratum without cutaneous tuberculosis, that is, nodular vasculitis. After treatment with calcineurin-inhibiting tacrolimus ointment, topical corticosteroids, and immunosuppressive oral azathioprine, the lesions improved.

Apocrine carcinoma is a rare malignant adnexal neoplasm. The differential diagnosis between apocrine carcinoma and cutaneous metastasis is often difficult. Here, we report a case of locally recurrent penile apocrine carcinoma initially diagnosed as metastatic adenocarcinoma of the colon. A 75-year-old man with a history of surgical resection due to sigmoid colon cancer and penile metastasis two years prior to this study presented with a nodule at the left penile base. He underwent a wide local resection of the penile mass under a suggested preoperative diagnosis of extra-mammary Paget's disease (EMPD) associated with previous sigmoid colon cancer. However, the previously and currently resected penile masses were identified as primary apocrine carcinoma upon hematoxylin and eosin (H&E) staining and immunohistochemical staining. Although the incidence is extremely rare, both clinicians and pathologists should be alert to the possibility of synchronous double primary apocrine carcinoma in cancer patients with malignant cutaneous lesions.

Introduction: Hepatocellular Carcinoma (HCC) is a major worldwide health problem due to its high incidence and mortality rates. The liver often becomes a site for metastasis from various primary locations, benefiting from its abundant blood supply. Distinguishing liver metastatic tumours from HCC can pose a diagnostic challenge, significantly impacting prognosis and treatment decisions. Aim: To differentiate between HCC, Intrahepatic Cholangiocarcinoma (ICC), and metastatic colonic adenocarcinoma in the liver using Hep par-1, Cytokeratin (CK) 7, CK19, and CK20 as immunohistochemical markers. The manual Tissue Microarray (TMA) technique was employed for present study. Materials and Methods: The present cross-sectional study was conducted in Department of Pathology at Government Stanley Medical College, Chennai, Tamil Nadu, India, spanning a three-year duration from July 2012 to June 2015. A total of 60 cases diagnosed histologically with HCC, ICC, and metastatic colonic adenocarcinoma in the liver were included. The manual TMA technique was used to create recipient blocks, and immunohistochemistry was performed to assess the expression of Hep par-1, CK7, CK19 and CK20. The sensitivity, specificity, Positive Predictive Value (PPV), and Negative Predictive Values (NPV) of these markers in HCC, ICC, and metastatic colonic adenocarcinoma in the liver were analysed and tabulated using statistical software Statistical Package for Social Sciences (SPSS) version 16.0. Results: The study included a total of 60 cases, with 40 (66.7%) males and 20 (33.3%) females, ranging in age from 27 to 73 years with a mean age of 51.3 years. Among the cases, there were 30 (50%) cases of HCC, 14 (23%) cases of ICC, and 16 (27%) cases of metastatic colonic adenocarcinoma in the liver. The sensitivity, specificity, and PPV of Hep par-1 in distinguishing HCC from ICC and metastatic deposits were 80%, 100%, and 100%, respectively. The NPV of Hep par-1 in distinguishing HCC from ICC and metastatic deposits was 70% and 72%, respectively. The sensitivity, specificity, PPV, and NPV of CK7 in distinguishing ICC from HCC were 3.3%, 50%, 6.3%, and 34.1%, respectively. The sensitivity, specificity, PPV, and NPV of CK19 in distinguishing HCC from ICC and metastatic deposits were 0%, 50%, 0%, and 33.3%. The sensitivity, specificity, PPV, and NPV of CK20 in distinguishing HCC from ICC and metastatic deposits were 0%, 53.3%, 0%, and 34.8%, respectively. Conclusion: In conclusion, it was found that a panel of markers including Hep par-1, CK7, CK19 and CK20 can differentiate between HCC, ICC, and metastatic colonic adenocarcinoma in the liver. This differentiation is crucial for determining the appropriate treatment for patients by understanding the exact behaviour of the tumour.

ADENOCARCINOMA OF THE LUNG MIMICKING MILIARY TB AND POTT DISEASE

Distinction between primary lung adenocarcinoma and metastatic adenocarcinoma from extrapulmonary origin in solitary pulmonary nodule (SPN) is crucial for cancer treatment. We investigated the predictive role of dual-time-point 18F-FDG PET/CT to distinguish primary and metastatic lung adenocarcinoma in SPN. A total of 96 consecutive patients with newly diagnosed SPN and biopsy-proven adenocarcinoma were enrolled in this study, retrospectively (54 male; 42 female; age 59.68 ± 8.2 years). They all underwent dual-time-point 18F-FDG PET/CT at 60 minutes (early) for whole body and 120 minutes (delayed) for chest region after FDG injection. Maximum standardized uptake values (early SUVmax and delayed SUVmax) and retention index (RI) were acquired for analysis. Final pathology results were confirmed by surgical specimens. Metastatic adenocarcinoma showed significantly higher early SUVmax, delayed SUVmax, and RI compared to primary lung adenocarcinoma. Delayed SUVmax and RI presented superior diagnostic performance for prediction of metastatic adenocarcinoma than early 18F-FDG PET/CT. Among metastatic adenocarcinoma, metastasis from colorectal origin showed significantly higher RI than from other origins. In addition, RI significantly predicted metastatic adenocarcinoma from colorectal cancer than early or delayed SUVmax. Dual-timepoint 18F-FDG PET/CT can be useful to distinguish primary and metastatic lung adenocarcinoma in SPN. Furthermore, it may also be useful to predict metastatic adenocarcinoma from colorectal origin.

We report a case of recalcitrant nodular vasculitis in a 23 years old male who was treated successfully with methotrexate. He presented to our Dermatology out Patient Department, Tribhuvan university teaching hospital with complaints of recurrent painful discharging ulcer over bilateral calf and lower legs of three years duration. The diagnosis of nodular vasculitis was made on the basis of the clinical presentation and the histopathological findings. The patient was treated with anti-tuberculosis treatment with initial good response; however the lesions persisted later on, despite completing the course of ATT. The patient did not respond to treatment with systemic corticosteroids also. On starting methotrexate, the lesion started healing within a period of two weeks and there was significant improvement in subsequent one month. This case report highlights the efficacy of methotrexate in the treatment of recalcitrant nodular vasculitis.