Invasive Cribriform Carcinoma Research Articles

GRIN3A: A biomarker associated with a cribriform pattern and poor prognosis in prostate cancer

Prostate cancer with a cribriform pattern, including invasive cribriform carcinoma (ICC) and/or intraductal carcinoma (IDC) is associated with a poor prognosis, and the underlying mechanisms are unclear. Therefore, we aimed to identify biomarkers for this feature. Using a radical prostatectomy cohort, we performed within-patient differential expression analyses with RNA sequencing data to compare samples with a cribriform pattern to those with non-cribriform Gleason pattern 4 (NcGP4; n=13). ACSM1, GRIN3A, PCDHB2, and REG4 were identified as differentially expressed, and validation was performed using real-time reverse transcription polymerase chain reaction (n=99; 321 RNA samples) and RNA in situ hybridization on tissue microarrays (n=479; 2047 tissue cores). GRIN3A was significantly higher expressed in cribriform pattern vs. NcGP4, when assessed within the same patient (n=27; p=0.005) and between different patients (n=83; p=0.001). Tissue cores with IDC more often expressed GRIN3A compared to ICC, NcGP4, and benign tissue (52 % vs. ≤ 32 %). When IDC and NcGP4 was compared within the same patient (173 pairs of tissue cores; 54 patients), 38 (22 %) of the tissue microarray core pairs had GRIN3A expression in only IDC, 33 (19 %) had expression in both IDC and NcGP4, 14 (8 %) in only NcGP4 and 88 (51 %) were negative in both entities (p=0.001). GRIN3A was as well associated with biochemical recurrence (log-rank, p=0.002). In conclusion, ectopic GRIN3A expression is an RNA-based biomarker for the presence of cribriform prostate cancer, particularly for IDC.

Abstract PO3-08-05: Prognostic value of multigene test to the patients with Hormone receptor-positive, HER2-negative breast cancer based on special histologic subtypes

Abstract Background: Special histologic subtypes of breast cancer, including mucinous and tubular, account for 25% of all invasive breast cancers. Multigene tests (MGT) play a crucial role in guiding adjuvant chemotherapy and predicting prognosis for the patients with Hormone receptor-positive HER2-negative breast cancer. This research aims to examine the results of multigene tests for special histologic subtype patients and review the prognosis of each group. Methods: A retrospective analysis was conducted on data from 133 patients with special histologic subtypes of breast cancer who underwent surgery at Severance Hospital between November 2013 and December 2022. Each patient underwent one type of MGT, including Oncotype Dx, MammaPrint, or EndoPredict. Patients were grouped in two groups according to histologic types, based on WHO classification. Favorable types consist of type A mucinous carcinoma, pure tubular carcinoma, invasive solid papillary carcinoma, encapsulated papillary carcinoma with invasion, invasive cribriform carcinoma, secretory carcinoma, and invasive carcinoma with apocrine differentiation. Unfavorable types included type B mucinous carcinoma, mucinous carcinoma with micropapillary feature or neuroendocrine differentiation, mixed IDC, ILC or invasive micropapillary carcinoma, mixed invasive solid papillary carcinoma, mixed invasive papillary carcinoma, and mixed invasive cribriform carcinoma with IDC. Results: Patients with favorable types accounted for 42.86% (57 patients), while patients with unfavorable types accounted for 57.14% (76 patients). Patients with unfavorable histologic subtypes of breast cancer tended to have a higher incidence of high-risk results in MGT, as well as a greater prevalence of multiple (multifocal, multicentric) cancer and higher histologic grade. In multivariate analysis using logistic regression, unfavorable types showed a significantly high ratio of having high risk on MGT compared to the favorable type (OR = 4.327, 95% CI 1.210 – 15.475, p-value = 0.024). Moreover, overall survival in unfavorable histologic types showed a statistically significant difference between high-risk and low-risk in Kaplan-Meier survival analysis (p-value = 0.001). Conclusions: Unfavorable subtypes have shown a significantly higher-risk result of MGT, and patients with unfavorable types of breast cancer and high-risk MGT results have exhibited the worst prognosis. Consequently, we can suggest that MGT can be used as a prognosis evaluation tool for certain special subtypes of breast cancer and further utilized to aid in treatment decisions. Citation Format: Seung Hye Yang, Jee Hyun Ahn, Suk Jun Lee, Jee Ye Kim, Hyung Seok Park, Seung Il Kim, Byeong Woo Park, Seho Park. Prognostic value of multigene test to the patients with Hormone receptor-positive, HER2-negative breast cancer based on special histologic subtypes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-08-05.

Lymphotropic Pattern of Prostate-specific Membrane Antigen–detected Metastases Among Biochemically Recurrent Radical Prostatectomy Patients with Cribriform Disease

BackgroundCribriform morphology portends worse oncologic outcomes, and has unique cellular intrinsic pathway alterations and tumor microenvironments that may impact metastatic spread patterns. ObjectiveTo determine whether the presence of cribriform morphology in prostatectomy specimens of patients with biochemical recurrence after radical prostatectomy (RP) is associated with the presence of metastasis on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and a distinct pattern of spread. Design, setting, and participantsA cross-sectional analysis was conducted of all prostate cancer patients with biochemical recurrence after RP undergoing 18F-DCFPyL-PET/CT between December 2018 and February 2021 at the Princess Margaret Cancer Centre. Outcome measurements and statistical analysisOutcomes were presence of any metastasis in the overall cohort and lymphatic versus bone/visceral metastases among patients with metastatic disease. The associations between the presence of intraductal (IDC) and/or invasive cribriform (ICC) carcinoma on the RP specimen and study outcomes were evaluated using logistic regression analyses. Results and limitationsThe cohort included 176 patients. IDC and ICC were observed in 77 (43.8%) and 80 (45.5%) RP specimens, respectively. The median time from RP to PSMA-PET/CT was 5.0 yr. The median serum prostate-specific antigen level at PSMA-PET/CT was 1.12 ng/ml. Overall, metastasis was observed in 77 patients, of whom 58 were had lymphatic-only metastasis. On a multivariable analysis, presence of IDC on RP was associated with increased odds of overall metastasis (odds ratio [OR]: 2.17; 95% confidence interval [CI]: 1.07–4.45; p = 0.033). Presence of ICC on RP was associated with significantly increased odds of lymphatic versus bone/visceral metastases (OR: 3.13; 95% CI: 1.09–21.7; p = 0.004). ConclusionsPresence of cribriform morphology on RP specimens of patients with biochemical failure after RP is associated with increased odds of PSMA-PET/CT–detected metastases with a lymphatic predominant pattern of spread. These findings have implications for the design and evaluation of post-RP salvage therapies. Patient summaryWe found that microscopic cribriform appearance correlates with disease spread on imaging in prostate cancer patients with recurrence and has a predilection for spread to lymph nodes, as opposed to bone or visceral organs.

A rare case of invasive cribriform carcinoma: Blessing in disguise

A rare case of invasive cribriform carcinoma: Blessing in disguise

Single cell analysis of cribriform prostate cancer reveals cell intrinsic and tumor microenvironmental pathways of aggressive disease

Cribriform prostate cancer, found in both invasive cribriform carcinoma (ICC) and intraductal carcinoma (IDC), is an aggressive histological subtype that is associated with progression to lethal disease. To delineate the molecular and cellular underpinnings of ICC/IDC aggressiveness, this study examines paired ICC/IDC and benign prostate surgical samples by single-cell RNA-sequencing, TCR sequencing, and histology. ICC/IDC cancer cells express genes associated with metastasis and targets with potential for therapeutic intervention. Pathway analyses and ligand/receptor status model cellular interactions among ICC/IDC and the tumor microenvironment (TME) including JAG1/NOTCH. The ICC/IDC TME is hallmarked by increased angiogenesis and immunosuppressive fibroblasts (CTHRC1+ASPN+FAP+ENG+) along with fewer T cells, elevated T cell dysfunction, and increased C1QB+TREM2+APOE+-M2 macrophages. These findings support that cancer cell intrinsic pathways and a complex immunosuppressive TME contribute to the aggressive phenotype of ICC/IDC. These data highlight potential therapeutic opportunities to restore immune signaling in patients with ICC/IDC that may afford better outcomes.

Large and small cribriform architecture have similar adverse clinical outcome on prostate cancer biopsies.

AimsInvasive cribriform and intraductal carcinoma (IDC) are associated with adverse outcome in prostate cancer patients, with the large cribriform pattern having the worst outcome in radical prostatectomies. Our objective was to determine the impact of the large and small cribriform patterns in prostate cancer biopsies.Methods and resultsPathological revision was carried out on biopsies of 1887 patients from the European Randomised Study of Screening for Prostate Cancer. The large cribriform pattern was defined as having at least twice the size of adjacent benign glands. The median follow‐up time was 13.4 years. Hazard ratios for metastasis‐free survival (MFS) and disease‐specific survival (DSS) were calculated using Cox proportional hazards regression. Any cribriform pattern was found in 280 of 1887 men: 1.1% IDC in grade group (GG) 1, 18.2% in GG2, 57.1% in GG3, 55.4% in GG4 and 59.3% in GG5; the large cribriform pattern was present in 0, 0.5, 9.8, 18.1 and 17.3%, respectively. In multivariable analyses, small and large cribriform patterns were both (P < 0.005) associated with worse MFS [small: hazard ratio (HR) = 3.04, 95% confidence interval (CI) = 1.93–4.78; large: HR = 3.17, 95% CI = 1.68–5.99] and DSS (small: HR = 4.07, 95% CI = 2.51–6.62; large: HR = 4.13, 95% CI = 2.14–7.98). Patients with the large cribriform pattern did not have worse MFS (P = 0.77) or DSS (P = 0.96) than those with the small cribriform pattern.ConclusionsBoth small and large cribriform patterns are associated with worse MFS and DSS in prostate cancer biopsies. Patients with the large cribriform pattern on biopsy have a similar adverse outcome as those with the small cribriform pattern.

A genomic classifier for prostate cancer correlates with adverse pathologic features: Transcriptomic features of cribriform and intraductal carcinoma of the prostate.

268 Background: Invasive cribriform and intraductal carcinoma (CF/IDC) portends an unfavorable prognosis for patients diagnosed with prostate cancer (CaP). Limited studies with small sample sizes have explored whether genomic classifiers are associated with IDC and/or CF status. We investigated the correlation between Decipher genomic risk score and IDC/CF status and assessed PCa transcriptomic features. Methods: We performed a retrospective review of CaP patients who had Decipher testing at a single high volume center between 2009-2020. The highest grade index lesion from radical prostatectomy specimens was identified by GU pathologists and used for Decipher testing. Genitourinary pathologists reviewed prostatectomy specimens for the presence of CF and IDC features. Patients were divided into three groups based on pathologic features, absent CF/IDC (CF-/IDC-), CF positive only (CF+/IDC-), and CF/IDC positive (CF+/IDC+). Categorical clinical, genomic, and pathologic variables were assessed using the Pearson Chi-Square test, quantitative with the Kruskal-Wallis test. Multivariable logistic regression was used to identify predictors of high-risk Decipher GC scores. The Kaplan-Meier method with log-rank was used to compare biochemical recurrence free survival. Differential gene expression and gene network analysis was used to identify genes and pathways associated with IDC/CF features. Results: 463 patients were included with a median follow-up of 25 months. Patients who were CF+/IDC+ had higher GC scores (CF+/IDC+: 0.77 vs. CF+/IDC-: 0.71 vs. CF-/IDC-: 0.61, p&lt;0.001). Patients who were CF+/IDC+ had a higher percentage of Gleason grade group &gt;3 (CF+/IDC+: 79% vs. CF+/IDC-: 52% vs. CF-/IDC-: 52%, p&lt;0.001). On multivariate logistic regression, predictors of high-risk GC score were presence of CF+/IDC+ features on final pathology (OR: 3.94, p&lt;0.001) and pathologic Gleason grade group &gt;3 (OR: 1.58, p=0.04). Transcriptomic analysis revealed that the hallmark androgen response pathway was significantly upregulated in CF+/IDC+ patients (Log fold change: 15.7, p&lt;0001). Conclusions: This is the largest series investigating the association of a clinically validated genomic classifier and pathologic features such as cribriform and intraductal carcinoma. These findings have implications for the use of genomic classifiers in settings where expert GU pathology is not readily available and in potentially unmasking adverse histology at the time of biopsy.[Table: see text]

Cribriform architecture outperforms Gleason pattern 4 percentage and tertiary Gleason pattern 5 in predicting the outcome of Grade Group 2 prostate cancer patients.

AimsGleason pattern 4 (GP4) percentage, invasive cribriform and/or intraductal carcinoma (IC/IDC) and the presence of tertiary Gleason pattern 5 (TP5) in radical prostatectomy (RP) specimens all aid in the risk stratification of Grade Group (GG) 2 prostate cancer patients. However, it is unclear to what extent these pathological features are mutually related and what are their individual values if they are investigated simultaneously. The aims of this study were: (i) to determine the mutual relationships of the GP4 percentage, IC/IDC and TP5 in GG2 RP specimens; and (ii) to assess their prognostic value for biochemical recurrence‐free survival (BCRFS).Methods and resultsOf 1064 RP specimens, 472 (44.4%) showed GG2 prostate cancer. Patients with ≥25% GP4 more frequently had IC/IDC (67.0% versus 43.9%; P < 0.001) and TP5 (20.6% versus 5.8%; P < 0.001) than those with <25% GP4. In unadjusted analysis, an increased GP4 percentage [hazard ratio (HR) 1.3; 95% confidence interval (CI) 1.0–1.6; P = 0.04] and IC/IDC (log rank P < 0.001) were associated with shorter BCRFS, whereas TP5 (P = 0.12) and a dichotomised (<25%, ≥25%) GP4 percentage (P = 0.10) were not. In multivariable analysis, IC/IDC was an independent prognostic factor (HR 1.9; 95% CI 1.2–2.9; P = 0.005) for BCRFS, whereas a continuous or dichotomised GP4 percentage and TP5 were not independent prognostic factors.ConclusionIn conclusion, a higher GP4 percentage in RP specimens was associated with more frequent IC/IDC and TP5. IC/IDC was an independent predictor for BCRFS, whereas the GP4 percentage and TP5 were not. These findings underscore the importance of routinely including the presence of IC/IDC in RP pathology reports.

PTEN expression and morphological patterns in prostatic adenocarcinoma.

Cribriform morphology, which includes intraductal carcinoma (IDCP) and invasive cribriform carcinoma, is an indicator of poor prognosis in prostate cancer. Phosphatase and tensin homologue (PTEN) loss is a predictor of adverse clinical outcomes. The association between PTEN expression and morphological patterns of prostate cancer is unclear. We explored the association between PTEN expression by immunohistochemistry, Gleason pattern 4 morphologies, IDCP and biochemical recurrence (BCR) in 163 radical prostatectomy specimens. IDCP was delineated from invasive cribriform carcinoma by p63 positive immunohistochemical staining in basal cells. Combined invasive cribriform carcinoma and IDCP were associated with a higher cumulative incidence of BCR [hazard ratio (HR) = 5.06; 2.21, 11.6, P < 0.001]. When including PTEN loss in the analysis, invasive cribriform carcinoma remained predictive of BCR (HR = 3.72; 1.75, 7.94, P = 0.001), while PTEN loss within invasive cribriform carcinoma did not. Glomeruloid morphology was associated with lower odds of cancer stage pT3 and lower cumulative incidence of BCR (HR = 0.27; 0.088, 0.796, P = 0.018), while PTEN loss within glomeruloid morphology was associated with a higher cumulative incidence of BCR (HR = 4.07; 1.04, 15.9, P = 0.043). PTEN loss within glomeruloid pattern was associated with BCR. The presence of any cribriform pattern was associated with BCR, despite PTEN loss not significantly associated with invasive cribriform carcinoma. We speculate that other drivers independent from PTEN loss may contribute to poor prognostic features in cribriform carcinoma.

MP50-03 PARAMETERS TO PREDICT UPGRADING TO GRADE GROUP 2 WITH INVASIVE CRIBRIFORM AND/OR INTRADUCTAL CARCINOMA OR HIGHER IN RADICAL PROSTATECTOMY SPECIMENS

INTRODUCTION AND OBJECTIVE:Grade Group (GG) and invasive cribriform and/or intraductal carcinoma (CR/IDC) are important parameters for clinical decision-making in prostate cancer. One of the inclus...

Clinicopathological analysis of invasive cribriform carcinoma of the breast, with review of the literature

Invasive cribriform carcinoma (ICC) is a rare type of a primary breast carcinoma. It is subdivided into two groups as pure and mixed types. There are limited studies comparing the pure and mixed ICC at present. We aim to investigate the clinicopathological, radiological, prognostic features, and survival outcomes of two types with reviewing the published literature. 16 pure ICC and 26 mixed ICC cases were evaluated. The population consisted of 41 female and 1 male patients. The only male patient was a pure ICC case. The median age was for pure and mixed type, 46.5 and 54 years, respectively. All ICCs were ER positive. All ICCs except one mixed ICC, were positive for PR. Only one mixed ICC was accepted HER2 positive (3+). Pure ICCs showed more favorable features than mixed ICCs such as lesser axillary lymph node involvement, lower grade, and proliferation index. Twenty-five patients had one of the following imaging methods; ultrasonography (US), mammography (MG), and magnetic resonance imaging (MRI). Irregular shape, hypoechogenicity, and spiculated margins were the most common US findings. Similarly, irregular shape+spiculated margin is the most common MG findings. The median follow-up time for pure and mixed ICC was 88 and 56.5 months, respectively. One mixed ICC case developed bone metastasis. One death occurred in each group. Reasons of death were unknown. The 5-year OS for both ICC groups was 100%. 10-year OS for pure and mixed ICCs was 100% and 90%, respectively. 5-year DFS was 100% for pure ICC, and 94% for mixed ICC.

Cribriform prostate cancer: Morphologic criteria enabling a diagnosis, based on survey of experts

Among four sub-patterns of Gleason grade 4 prostate cancer, voluminous evidence supports that the cribriform pattern holds an unfavorable prognostic impact, as compared with poorly-formed, fused, or glomeruloid. The International Society of Urological Pathology (ISUP) recommends specifying whether invasive grade 4 cancer is cribriform. Recently, ISUP experts published a consensus definition of cribriform pattern highlighting criteria that distinguish it from mimickers. The current study aimed to analyze morphologic features separately to identify those that define the essence of the cribriform pattern. Thirty-two selected photomicrographs were classified by 12 urologic pathologists as: definitely cribriform cancer, probably cribriform, unsure, probably not cribriform, or definitely not cribriform. Consensus was defined as 9/12 agree or disagree, with ≤1 strongly supporting the opposite choice. Final consensus was achieved in 21 of 32 cases.Generalized estimating equation (GEE) model with logit link was fitted to estimate effect of multiple morphologic predictors. Fisher exact test was used for categorical findings.Presence of intervening stroma precluded calling cribriform cancer (p = 0.006). Mucin presence detracted (p = 0.003) from willingness to call cribriform cancer (only 3 cases had mucin). Lumen number was associated with cribriform consensus (p = 0.0006), and all consensus cases had ≥9 lumens. Predominant papillary pattern or an irregular outer boundary detracted (p = NS).Invasive cribriform carcinoma should have absence of intervening stroma, and usually neither papillary pattern, irregular outer boundary, nor very few lumens. Setting the criteria for cribriform will help prevent over- or undercalling this important finding.

Clinical characteristics and overall survival prognostic nomogram for invasive cribriform carcinoma of breast: a SEER population-based analysis

BackgroundThe prognositc factors in patient with invasive cribriform carcinoma (ICC) of breast is still remain controversal. The study aims to establish a nomogram to predict the survival outcomes in patients with ICC based on the Surveillance, Epidemiology and End Results (SEER) database.MethodsWe retrieved SEER database for clinical data about patients including ICC and infiltrating ductal carcinoma (IDC) from 2004 to 2015. Kaplan-Meier survival was used to compare the difference survival outcomes between ICC and IDC. ICC patients were randomly allocated to training cohort and validation cohort. A nomogram was built to predict individual patient’s 3-year and 5-year survival status for ICC. The established TMN model and the newly established nomogram was further evaluated by the concordance index (C-index) and the decision curve analysis (DCA).ResultsComparing the baseline clinical data between IDC and ICC, a significant of smaller tumor mass, less infiltrated lymph nodes, lower metastases rate, better tumor differentiation degree, higher proportion of estrogen receptor (ER) and progesterone receptor (PR) positive and lower rate of chemotherapy and radiotherapy was found in ICC. Age at diagnosis, marriage status, tumor location, T stage, M stage, ER status, surgery were independent significant prognostic factors for the overall survival (OS). A significantly higher C-index was found in nomogram compared with established TNM model in validation cohort.ConclusionsThe prognosis of ICC patients is better than that of IDC patients. The nomogram is recommended for future patient with ICC to survival analysis.

Unusual case of Invasive Cribriform Carcinoma of Breast (ICC)

Background: Invasive cribriform carcinoma (ICC) is one of the rare variants of invasive ductal carcinoma of breast accounting for 0.3%-0.8% of these cases. It has low malignant potential with nodal metastases or vascular invasion hardly ever seen and is therefore known to carry an excellent prognosis. Case Report: We report here a case of 58 year old lady who presented as a post-operative case of carcinoma left breast with recurrence after lumpectomy. The histopathology showed a dominant cribriform pattern of monomorphic tumor cells along with extensive perineural infiltration and lymphovascular invasion that prompted us to think of it initially as an adenoid cystic carcinoma (ACC) but was later corroborated as an ICC on immunohistochemistry. Conclusion: To the best of our knowledge and search of literature, this is the first case report of an ICC portraying such an aggressive behaviour.

Cribriform architecture in radical prostatectomies predicts oncological outcome in Gleason score 8 prostate cancer patients

The Gleason score is an important parameter for clinical outcome in prostate cancer patients. Gleason score 8 is a heterogeneous disease including Gleason score 3 + 5, 4 + 4, and 5 + 3 tumors, and encompasses a broad range of tumor growth patterns. Our objective was to characterize individual growth patterns and identify prognostic parameters in Gleason score 8 prostate cancer patients. We reviewed 1064 radical prostatectomy specimens, recorded individual Gleason 4 and 5 growth patterns as well as presence of intraductal carcinoma, and evaluated biochemical recurrence- and metastasis-free survival. Gleason score 8 disease was identified in 140 (13%) patients, of whom 76 (54%) had Gleason score 3 + 5, 46 (33%) 4 + 4, and 18 (13%) 5 + 3 disease. Invasive cribriform and/or intraductal carcinoma (n = 87, 62%) was observed more frequently in Gleason score 4 + 4 (93%) than 3 + 5 (47%; P < 0.001) and 5 + 3 (44%; P < 0.001) patients. Gleason pattern 5 was present in 110 (79%) men: as single cells and/or cords in 99 (90%) and solid fields in 32 (29%) cases. Solid field pattern 5 coexisted with cribriform architecture (23/32, 72%) more frequently than nonsolid pattern 5 cases (36/78, 46%, P = 0.02). In multivariable analysis including age, prostate-specific antigen, pT-stage, surgical margin status, and lymph node metastases, presence of cribriform architecture was an independent parameter for biochemical recurrence-free (hazard ratio (HR) 2.0, 95% confidence interval (CI) 1.0–3.7; P = 0.04) and metastasis-free (HR 3.5, 95% CI 1.0–12.3; P = 0.05) survival. In conclusion, invasive cribriform and/or intraductal carcinoma occurs more frequently in Gleason score 4 + 4 prostate cancer patients than in Gleason score 3 + 5 and 5 + 3, and is an independent parameter for biochemical recurrence and metastasis. Therefore, cribriform architecture has added value in risk stratification of Gleason score 8 prostate cancer patients.

Temporary spontaneous regression of male breast cancer: a case report

BackgroundSpontaneous regression (SR) of a malignant tumor is the partial or complete disappearance of primary or metastatic tumor tissue in the absence of treatment, which can be temporary or permanent. Here, we report an extremely rare case of male breast cancer that exhibited temporary SR followed by reappearance 8 months after tumor disappearance.Case presentationA 70-year-old man presented at our hospital with a primary complaint of pain and a lump in his left breast. Ultrasonography revealed a hypoechoic lesion measuring 12 mm × 10 mm × 8 mm. Fine-needle aspiration cytology revealed numerous necrotic and degenerated cells and few sheet-like clusters of atypical ductal epithelial cells. The atypical cells had mildly enlarged nuclei with nucleoli, were focally overlapped and formed tubular patterns. The cytological diagnosis indicated a suspicion of malignancy. Core needle biopsy (CNB) revealed necrotic and degenerated cells with microcalcification. The pathological diagnosis was indeterminate because there was no area of viable atypical cells. An excisional biopsy of the left breast lesion was scheduled one month later. However, it was difficult to detect the tumor during physical examination and ultrasonography performed 1 month after the patient’s first visit. The operation was canceled, and the patient received follow-up observation. After 8 months of follow-up, ultrasonography and computed tomography (CT) revealed reappearance of a 0.6-cm-diameter breast tumor in the same place. CNB was performed again and revealed invasive ductal carcinoma. A total mastectomy with sentinel lymph node biopsy was performed 13 months after the first tumor disappeared. Histopathological examination revealed invasive cribriform carcinoma without sentinel lymph node metastasis. The patient did not have any complications, and adjuvant therapy with tamoxifen was started. The patient was alive without recurrence 7 months after surgery.ConclusionsTemporary SR followed by tumor reappearance can occur in breast cancer cases, and it is important to follow patients even if their breast tumor has seemingly disappeared. When breast tumors disappear without treatment, clinicians must be aware of the possibility of SR of cancer and should follow the patient for early detection of tumor reappearance.

Inter-observer variability of cribriform architecture and percent Gleason pattern 4 in prostate cancer: relation to clinical outcome

The Grade group is an important parameter for clinical decision-making in prostate cancer. Recently, percent Gleason pattern 4 and presence of invasive cribriform and/or intraductal carcinoma (CR/IDC) have been recognized for their independent predictive value for prostate cancer outcome. There is sparse data on the inter-observer agreement for these pathologic features in practice. Our objectives were to investigate inter-observer variability of percent Gleason pattern and CR/IDC and to relate individual tumour scores to clinical outcome. Our cohort included 80 consecutive radical prostatectomies with a median follow-up 87.1 months (interquartile range 43.3–119.2), of which the slide with largest tumour volume was scored by six pathologists for Grade group (four tiers: 1, 2, 3 and 4/5), percent Gleason pattern 4 (four tiers: 0–25%, 26–50%, 51–75% and 76–100%) and presence of CR/IDC (two tiers: absent, present). The individual assignments were related to post-operative biochemical recurrence (20/80). Inter-observer agreement was substantial (Krippendorff’s α 0.626) for assessment of Grade group and moderate for CR/IDC (α 0.507) and percent Gleason pattern 4 (α 0.551). For each individual pathologist, biochemical recurrence rates incremented by Grade group and presence of CR/IDC, although such relation was less clear for percent Gleason pattern 4. In conclusion, inter-observer agreement for CR/IDC and percent Gleason pattern 4 is lower than for Grade groups, indicating awareness of these features needs further improvement. Grade group and CR/IDC, but not percent Gleason pattern 4 was related to biochemical recurrence for each pathologist, indicating overall validity of individual grade assignments despite inter-observer variability.

The 2019 International Society of Urological Pathology (ISUP) Consensus Conference on Grading of Prostatic Carcinoma

Five years after the last prostatic carcinoma grading consensus conference of the International Society of Urological Pathology (ISUP), accrual of new data and modification of clinical practice require an update of current pathologic grading guidelines. This manuscript summarizes the proceedings of the ISUP consensus meeting for grading of prostatic carcinoma held in September 2019, in Nice, France. Topics brought to consensus included the following: (1) approaches to reporting of Gleason patterns 4 and 5 quantities, and minor/tertiary patterns, (2) an agreement to report the presence of invasive cribriform carcinoma, (3) an agreement to incorporate intraductal carcinoma into grading, and (4) individual versus aggregate grading of systematic and multiparametric magnetic resonance imaging–targeted biopsies. Finally, developments in the field of artificial intelligence in the grading of prostatic carcinoma and future research perspectives were discussed.

Histological pattern of breast diseases in children and adolescents in North Central Nigeria

Background: Breast lesions are said to be rare and predominantly benign in the pediatric population. However, several case reports of malignant breast lesions in this demography exist, hence, the need to carefully examine breast masses when seen in children and adolescents to ascertain their nature. Aim: The aim of this study is to document the frequency, sex, and age distribution of the histologic subtypes of breast diseases seen in children and adolescents in a district hospital. Patients and Methods: Data were collated retrospectively from patients' request forms and duplicate copies of histology reports of all cases of breast lesions seen over a 5-year period at the pathology unit of Asokoro District hospital, Abuja, North Central Nigeria. Data were analyzed using Microsoft Excel, expressed using measures of central tendencies and percentages, and displayed using simple tables. Results: One-hundred and thirty-six cases of breast lesions were seen in the children and adolescent population (≤19 years), representing 16% of all the breast specimens during the study period. Females accounted for 97% with female-to-male ratio of 33:1. Their ages ranged from 10 to 19 years with modal age at presentation of 16 years. One (0.74%) case of invasive cribriform carcinoma was seen in a 17-year old boy. They presented as unilateral breast lesions in 88.6%, bilateral lesions in 9.6%, and unstated in 5.8% of patients, respectively. The most common lesion was fibroadenoma (74.3%), followed by fibrocystic change (10.3%). Conclusion: Breast lesions are common among older children and adolescents in our environment, mostly benign in nature and strikingly affect females. Fibroadenoma was the most common histologic lesion seen.

Improved Prostate Cancer Biopsy Grading by Incorporation of Invasive Cribriform and Intraductal Carcinoma in the 2014 Grade Groups

BackgroundGrade groups (GGs) are an important parameter for therapeutic decision making in prostate cancer (Pca) patients. Invasive cribriform and/or intraductal carcinoma (CR/IDC) has an independent prognostic value for disease outcome, but are not included in the GG limiting their clinical use. ObjectiveTo perform a proof-of-principle study incorporating CR/IDC in the current GG. Design, setting, and participantsAll prostate biopsies of 1031 men with screen-detected Pca between 1993 and 2000 were reviewed for the current GG (ranging from 1 to 5) and CR/IDC. The cribriform grade (cGrade) was equal to the GG if CR/IDC was present and GG minus 1 if not. GG1 was cGrade1 if intraductal carcinoma was absent. InterventionBiopsy review for GG and CR/IDC. A total of 406 patients had received radical prostatectomy (RP), 508 radiotherapy (RT), 108 surveillance, and eight hormonal therapy, and the treatment was unknown for one patient.Outcome measurements and statistical analysis disease-specific survival (DSS), metastasis-free survival (MFS), and biochemical recurrence–free survival (BCRFS) after 15.1 yr (interquartile range 10.9–19.7 yr) follow-up were compared using Harrell’s C-statistic. Results and limitationsThe biopsy GGs were 486 GG1, 310 GG2, 104 GG3, 64 GG4, and 67 GG5; cGrade distributions were 738 cGrade1, 102 cGrade2, 91 cGrade3, 58 cGrade4, and 42 cGrade5. The cGrade had a better discriminative value than the GG for DSS (C-index 0.79; 95% confidence interval 0.74–0.83 vs 0.76; 0.71–0.82) and MFS (0.79; 0.74–0.84 vs 0.77; 0.72–0.82). The discriminative value for BCRFS after RP and RT was similar for both models. Different diagnostic, such as use of sextant biopsies, and therapeutic strategies in the 1990s are the limitations of this study. ConclusionsThe cGrade is a simple Pca grade modification with better discriminative values for DSS and MFS than the GG, particularly impacting decision making in men with current GG2 Pca. Patient summaryMicroscopic grading is an important factor for decision making in prostate cancer (Pca) patients. We show that a simple grade modification better predicts Pca outcome and might improve treatment choices.