Background Papillary renal cell carcinoma (pRCC) is the second most common histological subtype of renal cell carcinoma and is considered a morphologically and molecularly heterogeneous tumor. Accurate classification and assessment of the immunohistochemical features of possible therapeutic targets are needed for precise patient care. We aimed to evaluate immunohistochemical features and possible therapeutic targets of papillary renal neoplasms
Methods We collected 140 papillary renal neoplasms from three different hospitals and conducted immunohistochemical studies on tissue microarray slides. We performed succinate dehydrogenase B, fumarate hydratase, and transcription factor E3 immunohistochemical studies for differential diagnosis and re-classified five cases (3.6%) of papillary renal neoplasms. In addition, we conducted c-MET, p16, c-Myc, Ki-67, p53, and stimulator of interferon genes (STING) immunohistochemical studies to evaluate their pathogenesis and value for therapeutic targets.
Results We found that c-MET expression was more common in pRCC (classic) (p = .021) among papillary renal neoplasms and Ki-67 proliferation index was higher in pRCC (not otherwise specified, NOS) compared to that of pRCC (classic) and papillary neoplasm with reverse polarity (marginal significance, p = .080). Small subsets of cases with p16 block positivity (4.5%) (pRCC [NOS] only) and c-Myc expression (7.1%) (pRCC [classic] only) were found. Also, there were some cases showing STING expression and those cases were associated with increased Ki-67 proliferation index (marginal significance, p = .063).
Conclusions Our findings suggested that there are subsets of pRCC with c-MET, p16, c-MYC, and STING expression and those cases could be potential candidates for targeted therapy.
Jinahn Jeong, Deokhoon Kim, Yeon-Mi Ryu, Ja-Min Park, Sun Young Yoon, Bokyung Ahn, Gi Hwan Kim, Se Un Jeong, Hyun-Jung Sung, Yong Il Lee, Sang-Yeob Kim, Yong Mee Cho
J Pathol Transl Med. 2024;58(5):229-240. Published online August 9, 2024
Background Bladder cancer is characterized by frequent mutations, which provide potential therapeutic targets for most patients. The effectiveness of emerging personalized therapies depends on an accurate molecular diagnosis, for which the accurate estimation of the neoplastic cell percentage (NCP) is a crucial initial step. However, the established method for determining the NCP, manual counting by a pathologist, is time-consuming and not easily executable.
Methods To address this, artificial intelligence (AI) models were developed to estimate the NCP using nine convolutional neural networks and the scanned images of 39 cases of urinary tract cancer. The performance of the AI models was compared to that of six pathologists for 119 cases in the validation cohort. The ground truth value was obtained through multiplexed immunofluorescence. The AI model was then applied to 41 cases in the application cohort that underwent next-generation sequencing testing, and its impact on the copy number variation (CNV) was analyzed.
Results Each AI model demonstrated high reliability, with intraclass correlation coefficients (ICCs) ranging from 0.82 to 0.88. These values were comparable or better to those of pathologists, whose ICCs ranged from 0.78 to 0.91 in urothelial carcinoma cases, both with and without divergent differentiation/ subtypes. After applying AI-driven NCP, 190 CNV (24.2%) were reclassified with 66 (8.4%) and 78 (9.9%) moved to amplification and loss, respectively, from neutral/minor CNV. The neutral/minor CNV proportion decreased by 6%.
Conclusions These results suggest that AI models could assist human pathologists in repetitive and cumbersome NCP calculations.
Miso Kim, Hyo Sup Shim, Sheehyun Kim, In Hee Lee, Jihun Kim, Shinkyo Yoon, Hyung-Don Kim, Inkeun Park, Jae Ho Jeong, Changhoon Yoo, Jaekyung Cheon, In-Ho Kim, Jieun Lee, Sook Hee Hong, Sehhoon Park, Hyun Ae Jung, Jin Won Kim, Han Jo Kim, Yongjun Cha, Sun Min Lim, Han Sang Kim, Choong-Kun Lee, Jee Hung Kim, Sang Hoon Chun, Jina Yun, So Yeon Park, Hye Seung Lee, Yong Mee Cho, Soo Jeong Nam, Kiyong Na, Sun Och Yoon, Ahwon Lee, Kee-Taek Jang, Hongseok Yun, Sungyoung Lee, Jee Hyun Kim, Wan-Seop Kim
J Pathol Transl Med. 2024;58(4):147-164. Published online January 10, 2024
In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.
Background Ductal adenocarcinoma (DAC) of the prostate is an uncommon histologic subtype whose prognostic factors and immunoprofile have not been fully defined. Methods: To define its prognostic factors and immunoprofile, the clinicopathological features, including biochemical recurrence (BCR), of 61 cases of DAC were analyzed. Immunohistochemistry was performed on tissue microarray constructs to assess the expression of prostate cancer-related and mammalian target of rapamycin (mTOR) signaling-related proteins. Results: During the median follow-up period of 19.3 months, BCR occurred in 26 cases (42.6%). DAC demonstrated a wide expression range of prostate cancer-related proteins, including nine cases (14.8%) that were totally negative for pan-cytokeratin (PanCK) immunostaining. The mTOR signaling-related proteins also showed diverse expression. On univariate analysis, BCR was associated with high preoperative serum levels of prostate-specific antigen (PSA), large tumor volume, predominant ductal component, high Gleason score (GS), comedo-necrosis, high tumor stage (pT), lymphovascular invasion, and positive surgical margin. High expressions of phospho-mTOR (p-mTOR) as well as low expressions of PSA, phospho-S6 ribosomal protein (pS6) and PanCK were associated with BCR. On multivariable analysis, GS, pT, and immunohistochemical expressions of PanCK and p-mTOR remained independent prognostic factors for BCR. Conclusions: These results suggest GS, pT, and immunohistochemical expressions of PanCK and p-mTOR as independent prognostic factors for BCR in DAC. Since DAC showed diverse expression of prostate cancer–related proteins, this should be recognized in interpreting the immunoprofile of DAC. The diverse expression of mTOR-related proteins implicates their potential utility as predictive markers for mTOR targeted therapy.
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BACKGROUND To standardize renal biopsy reporting and diagnosis, The Renal Pathology Study Group of the Korean Society of Pathologists (RPSKSP) has developed a renal pathology reporting format for the native and allograft kidney. METHODS A consensus checklist of a provisional renal biopsy format was sent to all members of the RPSKSP. Feed back opinions regarding the practical application of the checklist to the diagnostic work were received. RESULTS Kidney biopsies require three essential examinations: by light microscopy, immunofluorescence (IF), and electron microscopy (EM). A final report of a renal biopsy should include information on specimen adequacy and a description of the morphologic change using a systematic semiquantitative method for each of the compartments, with optional separate IF and EM reports. CONCLUSIONS A standard renal biopsy report format is important in establishing clinicopathologic correlations, making reliable prognostic considerations, comparing the findings in sequential biopsies and evaluating the effects of therapy.
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BACKGROUND Second opinion diagnosis of outside pathology slides is a common practice for efficient and proper patient management. We analyzed cytology slides from outside hospitals submitted for a second opinion diagnosis to determine whether the second opinion diagnosis had any influence on patient care. METHODS We reviewed 1,153 outside cytology slides referred to Asan Medical Center for second opinions from January, 2007, to December, 2007. All cases were categorized into three groups; no diagnostic discrepancy, minor diagnostic discrepancies (no impact on the management), and major diagnostic discrepancies (significant impact on the management and subsequent follow-up). RESULTS The thyroid was the most common organ system (933 cases, 80.9%). Forty cases (3.6%) belonged to the major diagnostic discrepancy group and 149 cases (12.8%) to the minor discrepancy group. For validation of second opinion diagnoses in major discrepancy cases, subsequent biopsy or surgical resection specimens and clinical information were reviewed, which were available in 29 cases. The second opinion diagnoses resulted in alteration of clinical management in 21 of 29 cases. CONCLUSION For all referred patients, second opinion diagnosis is important and mandatory for appropriate patient care.
BACKGROUND Renal cell carcinoma (RCC) is notorious for its high metastatic potential, and 30% of RCC patients present with metastatic disease at the initial presentation and 50% of them will develop metastasis or recurrence after radical surgery. METHODS In an attempt to identify the best predictive marker(s) for metastasis in patients with clear cell RCCs (CRCCs), we examined the expression patterns of 7 metastasis/prognosis-related markers by constructing a tissue microarray including primary CRCC specimens from 30 metastatic and 60 nonmetastatic CRCCs. The markers we studied were Ki-67, MUC1, CD44s, PTEN, gelsolin, CA9 and p53. RESULTS The expressions of Ki-67, PTEN, CD44s, gelsolin and p53 were increased, whereas those of MUC1 and CA9 were decreased in the metastatic CRCCs compared with the non-metastatic CRCCs. The receiver operating characteristic curve-area under the curve (AUC) value of Ki-67 was 0.671, which was the highest among the 7 markers. The optimal cut-off value, sensitivity and specificity of the Ki-67 expression were 1.67%, 86.7% and 41.7%, respectively. CONCLUSIONS These results demonstrate that the Ki-67 expression was increased in metastatic CRCCs, and it had the highest predictive value among the 7 markers. This suggests that Ki-67 could be an excellent predictive marker for metastasis in CRCC patients.
BACKGROUND We wanted to find an adjunctive marker(s) in renal allograft biopsies for predicting acute cellular rejection (ACR), and so the expression patterns of immune-related molecules were compared between ACR, borderline ACR and non-ACR cases. METHODS The expression patterns of Fas ligand (FasL), HLA-DR, granzyme B, caspase-3, CD56, interferon stimulated growth factor-3 (ISGF-3), and CD53 were assessed via immunohistochemical study in 75 allograft biopsies from patients with ACR (n=19), borderline ACR (n=22), and non-ACR (n=34). RESULTS Compared to those of the non-ACR group, the ACR group revealed an elevated number of FasL positive interstitial inflammatory cells, HLA-DR positive tubular inflammatory cells, cytoplasmic caspase-3 positive tubular epithelial cells, granzyme B positive interstitial mononuclear inflammatory cells and CD53 positive interstitial inflammatory cells. The expression patterns of the borderline ACR group were similar to those of non-ACR group, except for the intensity of FasL in the tubular epithelial cells. CONCLUSIONS Immunohistochemical investigations of the adjunctive markers FasL, HLA-DR, granzyme B, caspase-3 and CD56 can be useful for making the diagnosis of ACR.
Mixed ductal-endocrine carcinoma of the pancreas is composed of ductal and endocrine carcinoma components and each component makes up a significant proportion in the primary tumor as well as in the tumor of metastatic sites. Mixed ductal-endocrine pancreatic carcinoma is exceptionally rare and, to our knowledge, only five cases have been reported in the literature. Recently we experienced a case of mixed ductal-endocrine pancreatic carcinoma with regional lymph node and hepatic metastases in a 63-year-old woman. Here, we report a case of mixed ductal-endocrine pancreatic carcinoma with a review of the literature.