Advancing the PD-L1 CPS test in metastatic TNBC: Insights from pathologists and findings from a nationwide survey.

Pembrolizumab has received approval as a first-line treatment for unresectable/metastatic triple-negative breast cancer (mTNBC) with a PD-L1 combined positive score (CPS) of ≥ 10. However, assessing CPS in mTNBC poses challenges. Firstly, it represents a novel analysis for breast pathologists. Secondly, the heterogeneity of PD-L1 expression in mTNBC further complicates the assessment. Lastly, the lack of standardized assays and staining platforms adds to the complexity. In KEYNOTE trials, PD-L1 expression was evaluated using the IHC 22C3 pharmDx kit as a companion diagnostic test. However, both the 22C3 pharmDx and VENTANA PD-L1 (SP263) assays are validated for CPS assessment. Consequently, assay-platform choice, staining conditions, and scoring methods can significantly impact the testing outcomes. This consensus paper aims to discuss the intricacies of PD-L1 CPS testing in mTNBC and provide practical recommendations for pathologists. Additionally, we present findings from a nationwide Italian survey elucidating the state-of-the-art in PD-L1 CPS testing in mTNBC.

Pulmonary metastasectomy for colorectal cancer: analysis of prognostic factors affecting survival.

BACKGROUND: Pulmonary metastasectomy is considered a standard procedure in the treatment of metastatic colorectal cancer (CRC). Different prognostic factors including multiple metastatic nodules, the presence of extra-pulmonary metastases and BRAF mutation status have been associated with poor survival. The aim of this study was to evaluate which factors influenced survival in CRC patients undergoing pulmonary metastasectomy by studying primary tumors and pulmonary metastases. METHODS: All patients treated for primary CRC who presented pulmonary metastases in a 10-year period were considered (group A). A control group treated for primary CRC who did not develop any pulmonary or extra-pulmonary metastases was taken for comparison (group B). Different prognostic factors including gender, age, tumor location, histological type, inflammatory infiltrate, BRAF, CDX2 and extra-pulmonary metastases were analyzed. Overall survival (OS) and patients' survival after pulmonary metastasectomy were also considered. RESULTS: Fifty-four patients were evaluated in group A and twenty-three in group B. In group A, BRAF immunohistochemistry did not significantly differ between primary tumors and pulmonary metastases; no difference of BRAF expression was found between group A and B. Even the expression of CDX2 was not significantly different in primary tumors and metastases. Similarly, in group B CDX2 did not significantly differ from primary CRC of group A. The most significant prognostic factor was the presence of extra-pulmonary metastases. Patients with extra-pulmonary metastases experienced a significant shorter survival compared to patients with pulmonary metastases alone (P=0.001 with log-rank test vs. P=0.003 with univariate Cox regression). Interestingly, patients with right pulmonary metastases presented a significant longer survival than those with left pulmonary metastases (P=0.027 with log-rank test vs. 0.04 with univariate Cox regression). CONCLUSIONS: The main prognostic factor associated with poor survival after lung resection of CRC metastases is a history of extra-pulmonary metastases. BRAF and CDX2 did not have a significant role in this small series of patients.

Cyst of the gastric wall arising from heterotopic pancreas: report of a case.

Heterotopia of pancreatic tissue is a common developmental anomaly, affecting predominantly the gastrointestinal tract. The case of a symptomatic cyst arising from the posterior gastric wall in a 40-year-old man is presented, undergoing laparoscopic gastric wedge resection. Pathology report described a cyst of the gastric wall lined by ductal pancreatic epithelium.

Very late recurrence of an apparently benign pheochromocytoma.

Pheochromocytoma is a tumor that has the probability to relapse in about 10% of surgically treated cases. Currently, the only recognized criteria of malignancy in these neoplasms are the evidence of metastasis at non-chromaffin sites. No reliable clinical or histopathological parameter has been, so far, identified to predict malignancy in patients with diagnosis of primary pheochromocytoma. Several authors has attempted to propose morphologic features to detect potentially malignant pheochromocytomas, but there are still too many reported cases of recurrence, also after decades, in tumors that, according to the current knowledge, are considered "benign". Here we report a case of recurrence, after 25 years, of a pheochromocytoma that had not enough criteria to be considered as malignant.

[Rhabdomyoma of the vagina. Case report and short literature review]. / Rhabdomyome du vagin. Revue de la littérature à partir d'un cas clinique.

The differential diagnosis of vaginal polypoid masses should take rhabdomyoma into consideration even it is an extremely rare tumor. The present report describes a vaginal cystic mass located in the anterior wall of an asymptomatic, 38-year-old, Caucasian, nulliparous woman. Local excision and subsequent pathological examination were performed. The final diagnosis was vaginal rhabdomyoma. The literature is reviewed and differential diagnosis are discussed.

Uterine carcinosarcoma metastatic to the lung as large-cell neuroendocrine carcinoma with synchronous sarcoid granulomatosis.

A 58-year-old woman underwent a curative total abdominal hysterectomy with bilateral salpingo-oophorectomy for a uterine carcinosarcoma. Fifteen months later, PET and CT scan revealed three pulmonary nodules and multiple lymphadenopathy. An atypical lung segmentectomy with dissection of the regional lymph nodes was performed. Two of the three nodules showed morphological and immunohistochemical profiles consistent with the diagnosis of large-cell neuroendocrine carcinoma (LCNEC). The third nodule, the surrounding pulmonary parenchyma and lymph nodes showed diffuse sarcoid granulomatosis. Re-review of the histology of the uterine carcinosarcoma revealed LCNEC morphology with immunohistochemical and genetic profiles identical to the lung cancers, finally deemed as metastatic deposits. Systemic sarcoidosis was ruled out. To our knowledge this is the first case of uterine carcinosarcoma with LCNEC features metastatic to the lung and occurring in association with sarcoid reaction.

Usefulness of a serological panel test in the assessment of gastritis in symptomatic children.

BACKGROUND: Non-invasive methods are advisable for the detection of Helicobacter pylori-related chronic gastritis in pediatric patients. Serum pepsinogens I and II (sPGII and sPGII), gastrin-17 (G-17) and anti-H. pylori antibodies (IgG-Hp) have been proposed as a 'serological gastric biopsy'. AIM: To assess H. pylori infection and to evaluate gastric mucosa status in a pediatric population by means of serological parameters such as sPGI, sPGII, G-17 and IgG-Hp. METHODS: 45 consecutively children evaluated for upper gastrointestinal symptoms were analyzed. All children were submitted to upper gastrointestinal endoscopy with biopsies. Serum samples were analyzed for IgG-Hp, sPGII, sPGI and G-17 (Biohit, Helsinki, Finland). RESULTS: 18 children had H. pylori-related mild or moderate non-atrophic chronic gastritis. They presented significantly higher mean levels of sPGII and of IgG-Hp than negative ones, either under or up to 10 years. sPGI showed significantly increased levels in H. pylori-positive patients only over 10 years. G-17 levels were not different between H. pylori-positive and -negative ones. The best cut-offs of IgG-Hp, sPGII and of product IgG-Hp x sPGII, to identify H. pylori infection, were 30 IU/l, 9 microg/l, and 241 IU/l x microg/l, respectively. The product IgG-Hp x sPGII identified H. pylori infection with a 100% sensitivity, 92% specificity, 90% positive predictive value and 100% negative predictive value. IgG-Hp and IgG-Hp showed a correlation (r = 0.94; p < 0.001). CONCLUSIONS: Combined analysis of sPGII and IgG-Hp antibody levels could be recommended as a non-invasive panel for the assessment of H. pylori-related histological alterations of gastric mucosa in childhood.

Usefulness of serum pepsinogens in Helicobacter pylori chronic gastritis: relationship with inflammation, activity, and density of the bacterium.

We sought to study the relationship between serum pepsinogens and different histopathologic features of Helicobacter pylori-related chronic gastritis. One hundred forty-nine consecutive dyspeptic patients underwent endoscopy with biopsies; serum pepsinogens I and II were measured by immunoassay. Serum levels of pepsinogens (sPG) were significantly correlated with H. pylori density both of the corpus (sPGI: r = 0.32, P < .001; sPGII: r = 0.56, P < .001) and antrum (sPGI: r = 0.41, P < .001; sPGII: r = 0.43, P < .001) as well as with chronic inflammation (sPGI: r = 0.26, P < .001; sPGII: r = 0.49, P < .001) and activity (sPGI: r = 0.38, P < .001; sPGII: r = 0.50, P < .001) in the antrum. Only sPGII was correlated with chronic inflammation (r = 0.44, P < .001) and activity (r = 0.40, P < .001) in the corpus. SPGI was inversely correlated with atrophy (r = -0.33, P < .001) and intestinal metaplasia (r = -0.37, P < .001) in the corpus. sPGII levels could be considered as markers of gastric inflammation all over in the stomach. sPGI levels are inversely related to atrophic body gastritis.

Recovery of gastric function after Helicobacter pylori eradication in subjects with body atrophic gastritis: prospective 4-year study.

BACKGROUND: The relationship between Helicobacter pylori (H. pylori) eradication and atrophic changes in the gastric mucosa has not yet been fully defined. Although studies report a partial restoration of serum pepsinogen I (sPGI) levels after eradication, it is not clear if this finding reflects gastric mucosal healing on a morphological level. AIM: To assess alterations in gastric function after H. pylori eradication on moderate/severe body atrophic gastritis by determination of sPGI levels. METHODS: Twenty-three dyspeptic patients, selected from 284 consecutive H. pylori positive patients, with histological features of moderate/severe body atrophic gastritis and sPGI < 25 microg/L (11 men, mean age: 51.8 years, range: 29-79 years), underwent an upper gastrointestinal endoscopy with gastric biopsies and sPGI determination at baseline. All patients underwent eradication therapy. Serum pepsinogen I was measured again after 6 months, and at 1, 2, 3 and 4 years after eradication therapy. RESULTS: Mean sPGI levels prior to eradication were 11.9 microg/L (range: 4-23 microg/L). Six months after eradication therapy, mean sPGI levels significantly increased to 17.4 microg/L (P = 0.04). At the completion of the study, 4 years after eradication, sPGI levels increased from 17.4 to 32.7 microg/L (P = 0.01). A significant progressive increase in sPGI levels was observed from 6 months to 1 year (17.4 to 23.9 microg/L) and from 1 to 2 years (23.9 to 26.0 microg/L, P = 0.01). Serum pepsinogen I levels higher than the cut-off value of 25 microg/L were observed at various time-points: 6.3% of patients at 6 months (1/16), 33.3% (5/15) at 1 year, 50% (7/14) at 24 months, 66.7% (6/9) at 36 months and 87.5% (7/8) at 4 years. CONCLUSION: After H. pylori eradication, subjects with body atrophic gastritis showed long-term improvement of physiological gastric function, reflected by significantly and continually increasing sPGI levels over a 4-year period.

Clinical usefulness of serum pepsinogen II in the management of Helicobacter pylori infection.

BACKGROUND: Serum pepsinogen II (sPGII) levels are known to increase during Helicobacter pylori infection. AIM: To assess H. pylori infection and success of H. pylori therapy by means of sPGII levels. METHODS: sPGII levels were determined in 156 H. pylori-positive and 157 H. pylori-negative consecutive patients with dyspeptic symptoms. Additionally, sPGII determination was performed in 70 H. pylori-positive patients 2 months after H. pylori eradication therapy. In 29 of these 70 patients, gastroscopy was performed to evaluate the effect of H. pylori therapy on gastric activity. RESULTS: H. pylori-positive subjects demonstrated a significantly higher mean of sPGII levels than H. pylori-negative subjects (16.8 +/- 7.4 vs. 8.6 +/- 3.7 microg/l; p < 0.001). The best sPGII cut-off for predicting H. pylori infection was 9.93 microg/l (sensitivity 83%, specificity 73%). The best cut-off values to evaluate success of therapy were: sPGII of 9.47 microg/l, a sPGII variation level (difference between baseline and after therapy) of 4.54 microg/l, and a sPGII Deltavalue (sPGII variation divided by sPGII before therapy) of 25% (sensitivity 93%, specificity 91%). CONCLUSIONS: sPGII levels may be used as a reliable marker of H. pylori infection in the initial diagnosis as well as to evaluate H. pylori eradication and subsequent changes in gastric inflammation.

Smooth Muscle Cell Abnormalities Associated with Gastric ECL Cell Carcinoids.

The histologic and immunohistochemical study of 45 ECL cell gastric carcinoids and of the extratumoral gastric mucosa revealed four variants of smooth muscle cell abnormalities: (1) hypertrophy of muscularis mucosae trapped within the tumors, a finding occurring in 76.5% of cases; (2) proliferation of stromal smooth muscle cells originating from the muscularas mucosae and mostly associated with tumor invasion of the submucosa (seen in 93.9% of cases with abundant stromal component of the tumors); (3) occurrence of frequent, prominent aggregates of smooth muscle cells in the lamina propria of the antral (but not of the fundic) mucosa of the stomach (found in 41.7% of cases); and (4) increased thickness of the extratumoral muscularis mucosae in the fundic (but not in the antral) mucosa of patients with gastric carcinoids. In addition, localized muscle cell proliferation was also associated with foci of micronodular hyperplasia of endocrine cells in the extratumoral mucosa. These findings were neither observed in control cases of gastric adenocarcinoma, gastric peptic ulcer, and duodenal peptic ulcer (10 unselected cases from each group) nor were they observed in 10 subjects with normal gastric mucosa collected at autopsy. With the possible exception of the increased thickness of the extratumoral fundic muscularis mucosae, which may be influenced by the mucosal inflammatory process, it is suggested that the present findings represent a proliferative response of smooth muscle cells to basic fibroblastic growth factor whose production by gastric carcinoids and their precursor lesions has recently been demonstrated.