Rosai-Dorfman disease is a self-limiting condition caused by histiocyte proliferation within the sinusoids of lymph nodes and in extranodal tissue. It is a rare disease, particularly in children, that progresses with extensive lymphadenopathy. This paper reports on the case of a 2-year-old child with progressive cervical lymphadenopathy associated with persistent fever and radiological findings suggestive of lymphoma. Histopathological and immunohistochemistry studies of a lymph node biopsy established the diagnosis of Rosai-Dorfman disease. Both lymphadenopathy and fever resolved spontaneously.

Background As Immune checkpoint inhibitors (ICPIs) are changing the standard-care in lung cancer with good clinical activities and durable responses, its indication must be based on the appropriate patient selection once only a fraction of patients has a response to these costly drugs. In larger cohorts the expression of programmed cell death–ligand 1 (PD-L1) has been associated with good clinical response of ICPIs in lung adenocarcinoma where the rate of high PD-L1 expression (defined as PD-L1tumor proportion score ≥ 50%) is ~ 30%, but once rare studies are available addressing the frequency of PD-L1 in populations outside those cohorts, we aimed to report the prevalence of PD-L1 and the frequency of patients with high PD-L1 expression utilizing data from a major pathology laboratory in Northeastern Brazil. Methods We retrospectively evaluated the PD-L1 expression in 158 surgically resected primary lung adenocarcinoma including 158 with anaplastic lymphoma kinase (ALK) expression. PD-L1 and ALK expression were evaluated by immunohistochemical analysis with the SP263 and D5F3 assays, respectively. Results Of the 158 samples analyzed, 94 (59.5%) had a PD-L1 tumor proportion score (TPS) < 1%, 38 (24.0%) had a PD-L1 TPS of 1–49% and 26 (16.5%) had a PD-L1 TPS of ≥50%. ALK expression was detected in 21 (13.3%) of the 158 tumor samples and 5 (3.2%) of them had a PD-L1 TPS of ≥50%. Conclusion The frequency of strong PD-L1 expression was lower than that previously reported in the trials where PD-L1 expression was used as a biomarker for patient selection. Also, considering that a subset of patients with ALK positivity had a strong PD-L1 expression, further studies will be required to examine the efficacy of PD-1/PD-L1 inhibitors in such patients.

Therapies targeting EGFR are effective in treating tumors that harbor molecular alterations; however, there is heterogeneity in long-term response to these therapies. We retrospectively analyzed protein expression of EGFR, Stat3, phospho-Akt, and phospho-Erk1/2 by immunohistochemistry in a series of resected cases from a single institution, correlated with clinicopathological variables. There were 96 patients, with the majority of cases being of low stage tumors (17 pT1a, 23 pT1b, 30 pT2a, and 18 pT2b). Histologic subtypes were 45 acinar predominant, 2 cribriform, 25 solid, 7 papillary, 11 lepidic, and 4 mucinous tumors. The EGFR score was higher in tumors with vascular invasion (P = 0.013), in solid and cribriform acinar histology, and in high stage tumors (P = 0.006 and P = 0.01). EGFR was more likely overexpressed in solid compared to lepidic tumors (P = 0.02). Acinar tumors had the highest rate of ERK1/2 positivity (19%). There was a strong correlation among positivity for ERCC1 and other markers, including STAT3 (P = 0.003), Akt (P = 0.02), and ERK1/ERK2 (P = 0.0005). Expression of molecules downstream to EGFR varied from 12% to 31% of tumors; however, the expression did not directly correlate to EGFR expression, which may suggest activation of the cascades through different pathways. The correlation of protein expression and the new lung adenocarcinoma classification may help in the understanding of activated pathways of each tumor type, which may act in the oncogenesis and drug resistance of these tumors.

Purpose:The study evaluates the clinical and pathological fi ndings of 16 patients with locally advanced penile carcinoma (PC) submitted to emasculation, and discusses questions related to the usefulness of bilateral orchiectomy. Materials and Methods: Between 1999 and 2010, 172 patients with PC were treated. Sixteen (9%) underwent emasculation. Data were retrieved from the institution's database including age, ethnicity, date of surgery, residential setting, level of schooling, time to diagnosis, type of reconstruction, complications, tumor stage and grade, vascular and perineural invasion along with invasion of corpus cavernosum, corpus spongiosum, testicles, scrotum and urethra. Results: A total of 16 patients (average: 63.1 years) with locally advanced PC were included. All were illiterate or semiliterate rural dwellers and 87% were white. The time to diagnosis was 8-12 months. The mean follow-up time was 31.9 months (1-119). By the time of the last follow-up, only seven patients (43.75%) were alive. Tumors were pT4 (n = 6), pT3 (n = 8), pT2 (n = 2), Grade I (n = 5) and Grade II (n = 11). The histopathological examination revealed invasion of the urethra (n = 13), scrotum (n = 5) and testicles (n = 1). The surgical margin was positive in one patient. Six patients (37.5%) had vascular invasion and 11 (68.7%) had perineural invasion. Currently, only one of the former is alive. Conclusions: The fi nding of focal microscopic testicular infi ltration in only one of 32 testicles, even in the presence of clinically apparent scrotal invasion, suggests that emasculation without bilateral orchiectomy is a safe treatment option for patients with locally advanced PC.

Background Advances in digital imaging in pathology and the new capacity to scan high-quality images have change the way to practice and research in surgical pathology. QuPath is an open-source pathology software that offers a reproducible way to analyze quantified variables. We aimed to present the functionality of biomarker scoring using QuPath and provide a guide for the validation of pathologic grading using a series of cases of urothelial carcinomas. Methods Tissue microarrays of urothelial carcinomas were constructed and scanned. The images stained with HE, CD8 and PD-L1 immunohistochemistry were imported into QuPath and dearrayed. Training images were used to build a grade classifier and applied to all cases. Quantification of CD8 and PD-L1 was undertaken for each core using cytoplasmic and membrane color segmentation and output measurement and compared with pathologists semi-quantitative assessments. Results There was a good correlation between tumor grade by the pathologist and by QuPath software (Kappa agreement 0.73). For low-grade carcinomas (by the report and pathologist), the concordance was not as high. Of the 32 low-grade tumors, 22 were correctly classified as low-grade, but 11 (34%) were diagnosed as high-grade, with the high-grade to the low-grade ratio in these misclassified cases ranging from 0.41 to 0.58. The median ratio for bona fide high-grade carcinomas was 0.59. Some of the reasons the authors list as potential mimickers for high-grade cases are fulguration artifact, nuclear hyperchromasia, folded tissues, and inconsistency in staining. The correlation analysis between the software and the pathologist showed that the CD8 marker showed a moderate (r = 0.595) and statistically significant (p < 0.001) correlation. The internal consistency of this parameter showed an index of 0.470. The correlation analysis between the software and the pathologist showed that the PDL1 marker showed a robust (r = 0.834) and significant (p < 0.001) correlation. The internal consistency of this parameter showed a CCI of 0.851. Conclusions We were able to demonstrate the utility of QuPath in identifying and scoring tumor cells and IHC quantification of two biomarkers. The protocol we present uses a free open-source platform to help researchers deal with imaging and data processing in the surgical pathology field.