Search

Objective: To determine the frequency of granulomatous inflammation within hepatocellular carcinoma (HCC) and its clinicopathologic associations. Material and Method: Fifty-eight HCCs (51 explants, 3 lobectomies, and 4 segmentectomies) were reviewed. Results: Five (8.6%) cases (F/M=1/4, mean age: 63.6) were identified with granulomas.1/5 had history of neoadjuvant therapy. 4/5 patients presented with early stage (pT1/2). All were well-differentiated (Grade1-2/4). The mean number of tumor foci was 3.6, with a median size of 2.2 cm. All of them had advanced fibrosis. No difference was identified from cases without granulomas (n=53) in terms of prognosis and aforementioned parameters (p> 0.05). Granulomas were mainly concentrated in peripheral parts of the tumors. One case with nodule-in-nodule formation had granulomas lined along the border of the inner nodule. In 2 cases, granulomas were identified in steatohepatitic areas, while another had clear cell change. Only 1 had necrotizing granulomas, none with acid resistant bacilli. Two cases revealed concomitant granulomas in the adjacent liver parenchyma in addition to the tumor stroma. Except for one with a history of tuberculosis, none of the cases had a granulomatous disease. Conclusion: This is the largest case series of HCCs with granulomas by far. Our data revealed neither clinicopathologic and prognostic difference nor definite etiology related to granulomas. Yet, association with steatotic and clear tumor cells suggests the role of cytoplasmic content, while distribution of granulomas points to host immune response. [ABSTRACT FROM AUTHOR]

Autoimmune hepatitis (AIH) is a chronic progressive autoimmune liver disease characterized by hypergammaglobulinemia, interface hepatitis, a female preponderance, and the presence of autoantibodies in most patients. The presence of HLA-DR3/DR4 and functional impairment in regulatory T cells are associated with AIH. However, AIH is a multifactorial complex disease. This report is a description of a case of seronegative AIH in a girl with chronic hepatitis, a high immunoglobulin E (IgE) level, perforating nodular dermatitis, and sheer eosinophilia. To re-evaluate the diagnosis, whole exon sequencing was performed. It was determined that the patient had ancestral haplotype A1-B8-DR3, which is associated with autoimmunity. Importantly, it was also noted that an undocumented point mutation (Ala627Thr) of the FMS-like tyrosine 3 kinase (FLT3) receptor was present. This FLT3 receptor gain-of-function mutation is associated with the activation of the mechanistic target of rapamycin (mTOR), and dendritic cell activation. In addition, a loss-of-function mutation in the melanocortin-3 receptor gene, which inhibits interleukin 4, was detected. The constellation of these immune deregulatory factors may have propagated auto-aggression of the liver, causing chronic hepatitis with AIH features. The findings of seronegativity with eosinophilia and a high IgE level led us to hypothesize that the pathognomonic mechanism in this case was unlike that of classic AIH pathophysiology. Since mTOR is constitutively activated, mTOR inhibitors may be a useful option to treat AIH and dermatitis. [ABSTRACT FROM AUTHOR]

Objective: The nature and clinicopathologic associations of Löwenstein-Buschke disease are unclear. Materials and Methods: 78 anal condylomatous lesions (=2 cm) were analyzed. Cases were classified based on size as "medium-large"(2-5 cm, n=59), "large" (5-10 cm, n=13) and "giant" (>10 cm, n=6). Results: Patients were predominantly males (male/female=70/8). The mean age was 38 years (range:20-66). Two distinct lining types were recognized: 1) Epidermal type, typically lacking overt koilocytotic change, with associated invasive carcinoma in 8%; 2) Mucosal type, often manifesting koilocytotic change, with associated invasive carcinoma in 21%. Three types of high-grade dysplasia were discerned: 1) Basaloid, 8/9 showing high-grade dysplasia/carcinoma in-situ but non-invasive lesions; 2) Keratinizing, innocuous-appearing, but 5/6 was associated with invasion; 3) Giant cell, showing scattered individual bizarre cells, with 3/5 showing invasive carcinoma. Overall, invasion was found in 14% of the cases. The bulbous, broad-based destructive pattern characterizing verrucous carcinomas of the upper aerodigestive tract was not observed. A statistically significant trend existed between the incidence of invasion and size: 8.5% for medium-large, 23% for large, and 50% for giant (p=0.02). There was no discernable trend in the depth of invasion relative to condyloma size. Conclusions: Our findings suggest that Löwenstein-Buschke lesions are mega versions of conventional condyloma. Being verrucoid, large and minimally invasive, they can be conceptually regarded as a form of verrucous carcinoma, but they do not display the histologic characteristics of verrucous carcinoma defined in the aerodigestive tract. They exhibit two types of linings: the mucosal type that often shows koilocytotic changes, and the epidermal type that can be difficult to recognize in biopsies. These lesions may be associated with invasive carcinoma, albeit limited in amount. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency of granulomatous inflammation within hepatocellular carcinoma (HCC) and its clinicopathologic associations., Material and Method: Fifty-eight HCCs (51 explants, 3 lobectomies, and 4 segmentectomies) were reviewed., Results: Five (8.6%) cases (F/M=1/4, mean age: 63.6) were identified with granulomas.1/5 had history of neoadjuvant therapy. 4/5 patients presented with early stage (pT1/2). All were well-differentiated (Grade1-2/4). The mean number of tumor foci was 3.6, with a median size of 2.2 cm. All of them had advanced fibrosis. No difference was identified from cases without granulomas (n=53) in terms of prognosis and aforementioned parameters (p > 0.05). Granulomas were mainly concentrated in peripheral parts of the tumors. One case with nodule-in-nodule formation had granulomas lined along the border of the inner nodule. In 2 cases, granulomas were identified in steatohepatitic areas, while another had clear cell change. Only 1 had necrotizing granulomas, none with acid resistant bacilli. Two cases revealed concomitant granulomas in the adjacent liver parenchyma in addition to the tumor stroma. Except for one with a history of tuberculosis, none of the cases had a granulomatous disease., Conclusion: This is the largest case series of HCCs with granulomas by far. Our data revealed neither clinicopathologic and prognostic difference nor definite etiology related to granulomas. Yet, association with steatotic and clear tumor cells suggests the role of cytoplasmic content, while distribution of granulomas points to host immune response.

Objective: The nature and clinicopathologic associations of Löwenstein-Buschke disease are unclear., Materials and Methods: 78 anal condylomatous lesions (≥2 cm) were analyzed. Cases were classified based on size as "medium-large"(2-5 cm, n=59), "large" (5-10 cm, n=13) and "giant" ( > 10 cm, n=6)., Results: Patients were predominantly males (male/female=70/8). The mean age was 38 years (range:20-66). Two distinct lining types were recognized: 1) Epidermal type, typically lacking overt koilocytotic change, with associated invasive carcinoma in 8%; 2) Mucosal type, often manifesting koilocytotic change, with associated invasive carcinoma in 21%. Three types of high-grade dysplasia were discerned: 1) Basaloid, 8/9 showing high-grade dysplasia/carcinoma in-situ but non-invasive lesions; 2) Keratinizing, innocuous-appearing, but 5/6 was associated with invasion; 3) Giant cell, showing scattered individual bizarre cells, with 3/5 showing invasive carcinoma. Overall, invasion was found in 14% of the cases. The bulbous, broad-based destructive pattern characterizing verrucous carcinomas of the upper aerodigestive tract was not observed. A statistically significant trend existed between the incidence of invasion and size: 8.5% for medium-large, 23% for large, and 50% for giant (p=0.02). There was no discernable trend in the depth of invasion relative to condyloma size., Conclusions: Our findings suggest that Löwenstein-Buschke lesions are mega versions of conventional condyloma. Being verrucoid, large and minimally invasive, they can be conceptually regarded as a form of verrucous carcinoma, but they do not display the histologic characteristics of verrucous carcinoma defined in the aerodigestive tract. They exhibit two types of linings: the mucosal type that often shows koilocytotic changes, and the epidermal type that can be difficult to recognize in biopsies. These lesions may be associated with invasive carcinoma, albeit limited in amount.