Microvessel density and angiogenesis in primary hepatic malignancies: Differential expression of CD31 and VEGFR-2 in hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

BACKGROUND: Microvessel density is an indicator of tumor-driven neoangiogenesis. Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) have distinct vascular patterns, which are also reflected in their imaging characteristics. Since a significant proportion of HCC are treated without biopsy confirmation, it is essential to discriminate HCC and ICC radiologically. The aim of our study was therefore to compare microvessel density and expression of VEGFR-2 in HCC and ICC, since these data may ultimately help us to better understand their imaging characteristics. Whereas CD31 documents vessel density, VEGFR-2 expression is an indicator of tumor-related neoangiogenesis. METHODS: CD31 and VEGFR-2 expressing microvessels were quantified on tissue microarrays of 95 resection specimens of HCC and 47 cases of ICC. Microvessel density was evaluated by counting immuno-reactive vascular structures both within the tumor and adjacent liver control tissue, respectively. Further 16 cases of ICC were immunostained for CD31 and VEGFR-2 on full sections. RESULTS: The frequency of VEGFR-2 (46.2/HPF; range 0-150) and CD31 (61.2/HPF; range 2.6-140) expressing vascular structures was significantly increased in HCC compared to adjacent liver parenchyma (VEGFR-2 33.3/HPF, range 0-87, CD31 21.4/HPF, range 0-78, both p < 0,001). ICC revealed significantly less VEGFR2-positive microvessels (15.4/HPF; range 2-77) compared to matched control tissue (42.3/HPF; range 4.6-109), whereas microvessel density with CD31 was comparable between ICC and adjacent liver (32.1/HPF; range 5.3-78 versus 28.0/HPF; range 5.3-57; p = 0.89). In ICC, the tumor-to-normal microvessel density ratio was 0.38 for VEGFR-2 and 1.24 for CD31. These ratios were nearly identical (VEGFR: 0.38; CD31: 0,97) for the 16 cases of ICC studied on whole sections, confirming the validity of the TMA approach. In contrast, ratios of VEGFR-2 and CD31 in HCC vs. adjacent liver were significantly higher (VEGFR: 2.23; CD31: 6.57). Expression of VEGFR-2 by tumor cells was not observed in any of the cases. CONCLUSIONS: HCC and ICC differ significantly in their microvessel density, confirming the hypovascular nature of ICC as compared to the hypervascularity of HCC. Of note, inverse tumor-to-normal ratios of microvascular VEGFR-2 expression between the two neoplasms indicate distinct features of neoangiogenesis. Whether these differences can be exploited for improvements in imaging of hepatic tumors and may play a role for anti-angiogenic treatment strategies requires further studies.

Hormone receptors analysis in idiopathic progressive subglottic stenosis.

OBJECTIVE: Idiopathic subglottic stenosis predominantly affects fertile and perimenopausal women. Estrogens and/or progesterone have been proposed as mediators of its pathogenesis by stimulating collagen deposition within the upper airway. We evaluated the presence and expression of estrogen-alpha (ER-α), estrogen-beta (ER-ß), and progesterone receptors (PR) in idiopathic stenotic patients. STUDY DESIGN: A retrospective analysis on 42 surgical specimens from idiopathic stenosis female patients (mean age, 52.4; age range, 31-79) and 28 gender- and age-matched controls. METHODS: Immunoreactivity of ER-α, ER-ß, and PR was calculated as the product of intensity (1 = weak, 2 = moderate, 3 = strong) and positive cell percentage (1-4, for < 10/10-50/50-80/ > 80%). This score was calculated on the stenotic and peristenotic tissues. Influence of menopausal status on hormonal expression and stenotic grade was tested. RESULTS: Stenosis showed ER-α overexpression versus peristenotic tissue and controls (score 6.6 ± 4.4, 0.3 ± 0.5, and 2.2 ± 1.5, respectively; P < 0.001). Overexpression was even more marked for progesterone receptors (score 8.3 ± 3.6, 0.8 ± 0.6, and 1.0 ± 0.7, respectively; P < 0.001). There was no expression of ER-ß in stenosis (score 0), whereas it was normally expressed in peristenotic tissue and controls (score 0.7 ± 0.5 and 0.5 ± 0.5; P < 0.001 vs. stenosis). Expression of ER-α was higher in postmenopausal stenotic patients (P < 0.01). This subgroup included a higher proportion of Cotton-Myer grade III stenosis than in premenopausal subjects (P < 0.001). CONCLUSION: An imbalance between ER-α, ER-ß, and PR is present in idiopathic stenosis patients. The hormonal background may be involved in inappropriate inflammation and increased stenosis susceptibility. Menopausal changes seem to play a role in both stenosis grade and receptor patterns. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:E72-E77, 2018.

Lymphoepithelioma-like carcinoma of the stomach: a case report and review of the literature.

A lymphoepithelioma-like carcinoma (LLC), characterized by a carcinoma with stromal heavy lymphocyte infiltration, is one of the histological patterns observed in patients with Epstein-Barr virus (EBV)-associated gastric carcinoma. Although this entity is hard to be recognized in the biopsy specimens, pathologists and clinicians should acknowledge this subset of gastric cancer because it generally has a better prognosis than other forms of EBV-associated gastric carcinomas and conventional gastric carcinomas. This might be due to the fact that the patient's inflammatory response may prevent the spread of tumor through the gastric wall and to the lymph nodes or remote organs.We report a case of EBV-positive, microsatellite stable LLC as a rare morphologic variant of gastric carcinoma. VIRTUAL SLIDES: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1360498724104351.

Clinicopathologic features of ductal carcinoma in situ in young women with an emphasis on molecular subtype.

Young women with ductal carcinoma in situ treated by breast-conserving therapy have a higher recurrence rate than do older women, and a younger age at diagnosis is associated with worse overall survival after recurrence. This study explores the clinical, pathologic, and immunohistochemical characteristics of ductal carcinoma in situ lesions diagnosed in women 40 years and younger with a focus on molecular subtypes to elucidate features that may contribute to the purported worse outcome for this patient population. Forty-one patients diagnosed with ductal carcinoma in situ at age 40 years and younger were identified over a 10-year period; 31 cases were used to construct tissue microarrays. The microarrays were labeled with antibodies to estrogen receptor, progesterone receptor, HER2, Ki-67, CK5/6, epidermal growth factor receptor, and p53 and subsequently classified as luminal A, luminal B, HER2, basal-like, or unclassifiable triple negative. All patients had high-grade (73.2%) or intermediate-grade (26.8%) ductal carcinoma in situ. The molecular subtype breakdown was 61.3% luminal A, 22.6% luminal B, 13% HER2, and 3.1% unclassifiable triple negative. The mean Ki-67 by subtype was 4.2%, 14%, 9.5%, and 50%, respectively. Mastectomy was performed in 33 patients (80%). Eight patients (20%) underwent excisional biopsy without subsequent mastectomy. In addition to a predominance of high-grade lesions, young patients had a high proportion of luminal B subtype, which may contribute to an increased rate of local recurrence in this population. A larger series is necessary to confirm the impact that the molecular subtypes of ductal carcinoma in situ in younger patients might have on outcome.