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AIMS Prostatic intraepithelial neoplasia-like (PIN-like) ductal carcinoma is a rare tumour characterised by often cystically dilated glands architecturally resembling high-grade PIN, but lacking basal cells. These tumours are frequently accompanied by grade group 1 acinar cancer and behave relatively indolently. In contrast, conventional ductal adenocarcinoma of the prostate is an aggressive variant comparable to grade group 4 acinar cancer. Here, we used targeted next-generation sequencing to molecularly profile PIN-like ductal carcinoma cases at radical prostatectomy. METHODS AND RESULTS Five PIN-like ductal carcinoma samples at radical prostatectomy with sufficient tumour tissue available were analysed for genomic alterations by targeted next-generation sequencing using the Johns Hopkins University (JHU) solid tumour panel. DNA was captured using SureSelect for 640 genes and sequenced on the Illumina HiSeq platform. Three of five (60%) of the PIN-like ductal carcinomas showed activating mutations in the RAS/RAF pathways, which are extraordinarily rare in conventional primary prostate carcinoma (

Background Mucinous adenocarcinoma is often considered a relatively poor prognostic group among adenocarcinomas of the lung and has a high rate of pulmonary recurrence. Pathologic parameters predicting poor outcome have not been extensively studied, including the presence of spread through alveolar spaces (STAS). Methods We retrospectively studied time to lung recurrence and time to distant metastasis in 30 mucinous lung tumors, in relationship to histologic parameters, including spread through alveolar spaces, tumor size, invasive size, % invasive size, growth pattern (solid or cribriform, acinar, papillary, micropapillary, and lepidic), type of mucin-producing cell, and TTF-1 positivity. Results Median follow-up was 40 months. There were 7 patients (23%) with lung recurrence (mean 22 months) and 7 (23%) with distant metastases (mean 3.7 months). Columnar / goblet cell type was inversely correlated with TTF-1 expression (p = 0.01). The only pathologic parameters associated with outcome were STAS for lung recurrence (p = .005) and solid/cribriform growth (≥ 20% of tumor) for distant metastasis (p = 0.003). Conclusions Mucinous adenocarcinomas of the lung are similar to non-mucinous prognostically, in that STAS and solid growth are poor prognosticators, for local and distant recurrence, respectively. The growth patterns of mucinous adenocarcinomas should be reported similar to reporting of non-mucinous adenocarcinomas.

We assessed the risk of locally aggressive behavior in pure Gleason score 6 (Grade Group 1) prostate cancer using contemporary grading criteria. To our knowledge this has been studied in only 1 prior cohort.We evaluated consecutive radical prostatectomy specimens from an academic institution, including those from 3,291 men with Gleason score 6 and 4,202 with Gleason score 3 + 4 = 7 (Grade Group 2) disease between 2005 and 2016. For dichotomous variables the Pearson chi-square test was used.Of the 3,288 Gleason score 6 cancer cases 128 (3.9%) showed focal extraprostatic extension compared to 593 of the 4,202 (14.1%) with Gleason score 3 + 4 = 7 (p0.0001). Of the 3,288 Gleason score 6 cancer cases 79 (2.4%) showed nonfocal extraprostatic extension compared to 639 of the 4,202 (15.2%) with Gleason score 3 + 4 = 7 (p0.0001). The incidence of focal extraprostatic extension with Gleason score 3 + 4 = 7 with less than 5% Gleason pattern 4 was 129 of 1,147 cases (11.2%), which was between Gleason scores 6 and 3 + 4 = 7 with greater than 5% Gleason pattern 4. The incidence of nonfocal extraprostatic extension in Gleason score 3 + 4 = 7 with less than 5% Gleason pattern 4 was 96 of 1,147 cases (8.4%), which was between Gleason scores 6 and 3 + 4 = 7 with greater than 5% Gleason pattern 4. One of the 3,290 Gleason score 6 cases (0.03%) showed seminal vesicle invasion compared to 93 of the 4,202 (2.2%) of Gleason score 3 + 4 = 7 (p 0.0001). A limitation of our study was its retrospective design.It is not rare for pure Gleason score 6 prostate cancer to locally extend out of the prostate 3.9% focally and 2.4% nonfocally. In extremely rare cases Gleason score 6 can be associated with seminal vesicle invasion and yet not lymph node metastases. Our overall findings support the argument for continuing to use the term cancer for these tumors.

Prostatic intraepithelial neoplasia like (PIN-like ductal) carcinoma are rare tumors characterized by crowded, often cystically dilated glands architecturally resembling high-grade prostatic intraepithelial neoplasia, lined by malignant pseudostratified columnar epithelium. The largest prior series studied 9 radical prostatectomies (RPs) and suggested a behavior similar to Gleason score 6. We sought to investigate this rare tumor within a larger series. PIN-like carcinoma cases were identified from in-house and consultation files from 2008 to 2017. A total of 190 total cases were identified (in-house cases n=8, 4.2%, consult cases n=182, 95.8%); the diagnosis of PIN-like carcinoma was made on needle biopsy (n=181), transurethral resection (n=5) and RP (n=4). The average age was 70 years. The average number of cores with involvement by PIN-like carcinoma was 2 (1 to 12). The average maximum percentage by a PIN-like carcinoma component of any core was 43.5% (5% to 90%). In 58/181 (32.0%) biopsy cases, due to selective parts having been submitted for consultation, it was unknown whether there was an association with acinar carcinoma. A total of 72 cases showed exclusively PIN-like carcinoma. Highest grade groups (GGs) on biopsies with known acinar or papillary/cribriform ductal carcinomas were GG1 (n=23, 45.1%), GG2 (n=14, 27.5%), GG3 (n=9, 17.6%), GG4 (n=4, 7.8%), and GG5 (n=1, 2.0%). Of 44 cases where the patient would be considered eligible for active surveillance, 18 (41.0%) underwent RP. RP slides were available in 16 cases; 3 (18.8%) cases diagnosed on biopsy did not show PIN-like carcinoma on review of RP slides. PIN-like carcinoma was present without an associated acinar tumor in 3 (23.1%) RPs; 2 showing tumors with large, cystic dilated glands extending into periprostatic tissue. In 7/13 cases (53.8%), the acinar component was the dominant tumor and the PIN-like carcinoma component was small (1 cm). The overall grade at RP was GG1 (5/13, 38.5%) and GG2 (8/13, 61.5%). In all cases with an acinar component, the acinar tumor was anatomically distinct from the PIN-like carcinoma tumor. The GGs of the separate acinar tumors were GG1 (6/10) and GG2 (4/10) with percent pattern 4 ≤5% in all 4 cases. No cases were associated with metastases to lymph nodes or seminal vesicle invasion. Extraprostatic extension was present in 6/13 (46.1%) cases, from the acinar component in 1 (7.7%) case and the PIN-like carcinoma component in 5 (83.3%) cases. In all 5 cases, there was a peculiar morphology of thin papillary projections into cystic dilated PIN-like carcinoma glands. Immunohistochemical expression of ERG was positive in 1/11 (9.1%) case. 1/11 (9.1%) case showed heterogeneous loss of PTEN. Overall, PIN-like carcinoma tumors are limited in size, not advanced in stage, not associated with high-grade cancer on RP, and show low rates of Gleason pattern 4 and TMPS-ERG rearrangement. Our study supports grading classic PIN-like carcinoma as Gleason pattern 3; at the current time we recommend grading thin papillary projections of PIN-like carcinoma as pattern 4. Longer term studies will be needed to determine the clinical significance of thin papillary projections in PIN-like carcinoma.

Newly-appearing lung nodules on surveillance imaging in patients with pre-existing lung cancer can present a diagnostic dilemma when attempting to differentiate between metastatic disease, infection, and other inflammatory conditions. Here we report a case of an EGFR-/ALK-/BRAF+ metastatic adenocarcinoma patient who underwent lung biopsy for evaluation of upper-lobe predominant lung nodules revealed to represent pulmonary Langerhans cell histiocytosis (PLCH). The patient was a heavy smoker and admitted to increase her smoking habit after initially learning about her diagnosis with lung cancer. Interestingly, despite the association of both lung adenocarcinoma and PLCH with the BRAFV600E mutation in smokers, pyrosequencing of the patient's PLCH lesions was negative for this mutation. Co-occurrence of PLCH with lung cancer is extremely rare. While most reported cases of PLCH tend to precede the occurrence of lung cancer, a minority of cases appear after a diagnosis of lung cancer has already been established and are thought to represent a local immunologic reaction to the tumor. It is therefore postulated that the appearance of PLCH lesions in this patient's lungs is a result of her increase in cigarette smoking, possibly augmented by co-existence of adenocarcinoma.