Invasive cribriform carcinoma of the breast presenting as an erythematous papule on the nipple: A case report.

Invasive cribriform carcinoma (ICC) is a rare form of invasive breast carcinoma with good prognosis. To date, case reports considering skin manifestations of ICC are scarce. We herein report a case of pure ICC presenting as an erythematous papule on the nipple with mammary Paget's disease in the epidermis. We aim to bring awareness to skin manifestation of ICC.

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.

Ductal, intraductal, and cribriform carcinoma of the prostate: Molecular characteristics and clinical management.

Prostatic acinar adenocarcinoma accounts for approximately 95% of prostate cancer (CaP) cases. The remaining 5% of histologic subtypes of CaP are known to be more aggressive and have recently garnered substantial attention. These histologic subtypes - namely, prostatic ductal adenocarcinoma (PDA), intraductal carcinoma of the prostate (IDC-P), and cribriform carcinoma of the prostate (CC-P) - typically exhibit distinct growth characteristics, genomic features, and unique oncologic outcomes. For example, PTEN mutations, which cause uncontrolled cell growth, are frequently present in IDC-P and CC-P. Germline mutations in homologous DNA recombination repair (HRR) genes (e.g., BRCA1, BRCA2, ATM, PALB2, and CHEK2) are discovered in 40% of patients with IDC-P, while only 9% of patients without ductal involvement had a germline mutation. CC-P is associated with deletions in common tumor suppressor genes, including PTEN, TP53, NKX3-1, MAP3K7, RB1, and CHD1. Evidence suggests abiraterone may be superior to docetaxel as a first-line treatment for patients with IDC-P. To address these and other critical pathological attributes, this review examines the molecular pathology, genetics, treatments, and oncologic outcomes associated with CC-P, PDA, and IDC-P with the objective of creating a comprehensive resource with a centralized repository of information on PDA, IDC-P, and CC-P.

A rare case of breast invasive cribriform carcinoma.

Although invasive ductal carcinoma accounts for 75% of all primary breast cancers diagnosed, there are other, more uncommon kinds, including invasive cribriform carcinoma (ICC). Invasive cribriform carcinoma has 2 subtypes: pure and mixed. Ultrasonography and magnetic resonance imaging are the best imaging methods for assessing the characteristics of breast ICC (MRI). Our goal in this article was to report a rare instance of breast ICC in a 38-year-old Vietnamese woman. During a clinical examination, a spherical mass in the left breast without ipsilateral axillary lymph nodes was seen. On ultrasonography, the lesion was classified as BI-RADS 4C. The lesion was with an apparent diffusion coefficient value of 0.46 × 10-3 mm2/s. Lesion showed a quick initial increase on dynamic T1-weighted imaging with contrast enhancement, followed by a wash-out in the delayed phase. The final histopathological findings confirmed the presence of ICC.

Reappraisal and literature review of primary cutaneous cribriform apocrine carcinoma.

Primary cutaneous cribriform apocrine carcinoma (PCCAC) is an exceedingly rare sweat gland carcinoma. Clinically, it most often presents as a singular, asymptomatic nodule or cyst on the extremities of middle-aged patients and follows an indolent course. Both visceral and cutaneous cribriform tumors exist in nature. While a cribriform pattern is well recognized in tumors of visceral organs, there is a paucity in the literature on the defining characteristics for primary cutaneous tumors. Consensus regarding diagnostic criteria, etiology, and management protocols has yet to be achieved. We conducted an extensive literature review using pre-determined search criteria, resulting in 12 identified case reports and series on PCCAC that were subsequently analyzed. All data were compiled to provide a comprehensive update on the existing information regarding clinical presentation, histopathology, and management of reported PCCACs, as well as differential diagnosis, controversial issues, and recommendations for future considerations.

Cribriform Patterned Lesions in the Prostate Gland with Emphasis on Differential Diagnosis and Clinical Significance.

Cribriform glandular formations are characterized by a continuous proliferation of cells with intermingled lumina and can constitute a major or minor part of physiologic (normal central zone glands), benign (clear cell cribriform hyperplasia and basal cell hyperplasia), premalignant (high-grade prostatic intraepithelial neoplasia), borderline (atypical intraductal cribriform proliferation) or clearly malignant (intraductal, acinar, ductal and basal cell carcinoma) lesions. Each displays a different clinical course and variability in clinical management and prognosis. The aim of this review is to summarize the current knowledge regarding the morphological features, differential diagnosis, molecular profile and clinical significance of the cribriform-patterned entities of the prostate gland. Areas of controversy regarding their management, i.e., the grading of Intaductal Carcinoma, will also be discussed. Understanding the distinct nature of each cribriform lesion leads to the correct diagnosis and ensures accuracy in clinical decision-making, prognosis prediction and personalized risk stratification of patients.

Invasive cribriform carcinoma of the breast detected incidentally on computed tomography: A case report.

Invasive cribriform carcinoma is a rare type of invasive breast carcinoma, and a few cases have been reported. Its features are a cribriform pattern resembling the histological structures of cribriform ductal carcinoma in situ and an excellent prognosis. However, the extent of progress for intraductal extension must be carefully evaluated.

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.

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

BACKGROUND: The 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. METHODS: We 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). RESULTS: Comparing 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. CONCLUSIONS: The prognosis of ICC patients is better than that of IDC patients. The nomogram is recommended for future patient with ICC to survival analysis.

A case of cribriform carcinoma of the skin: a newly described rare condition.

Primary cribriform carcinoma of the skin is an indolent, rare, adnexal tumor. Although its malignant potential remains uncertain, no recurrence or metastasis has been reported. A 33-year-old man presented with a solitary, erythematous, subcutaneous nodule on the right knee. The clinical impression was epidermal cyst, and the resected tumor demonstrated a well-circumscribed mass in the dermis and subcutis. The tumor was composed of two regions: a solid component and a cribriform component. The solid component (90%) showed multiple solid nests of epithelial cells. Individual cells had large, oval-to-round, hyperchromatic, pleomorphic nuclei with a nuclear groove. The cribriform component (10%) showed similar neoplastic cells with many prominent lumina. Some lumina had an eosinophilic substance that exhibited a positive periodic acid-Schiff reaction. No recurrence or metastasis was observed within a followup period of eight months after excision. In conclusion, we report the first case of primary cribriform carcinoma of the skin in Korea.

Clinicopathological and molecular characteristics of prostate cancer diagnosed in young men aged up to 45 years.

AIMS: To characterise and compare the poorly understood clinicopathological and molecular characteristics of prostatic adenocarcinoma (PCa) in very young patients. METHODS AND RESULTS: We compared the clinicopathological and molecular characteristics of PCa diagnosed in 90 patients aged ≤45 years with those of PCa diagnosed in 200 patients of typical screening age (i.e. 60-65 years). Patients diagnosed at a younger age had a higher frequency of a family history of PCa and lower prostate-specific antigen (PSA) levels than those diagnosed at regular screening age. There were no statistically significant differences in clinical stage or pathological characteristics of the core biopsy specimens between the groups. Young patients had a higher frequency of Grade Group 1 disease at radical prostatectomy. A subset of 13 aggressive PCa cases from young patients underwent successful DNA-based next-generation sequencing. In all, 46.2% (6/13) had TMPRSS2 rearrangements and 23.1% (3/13) had relevant pathogenic variants in DNA damage repair genes, including a mismatch repair-deficient case with biallelic inactivation of MLH1. No statistically significant differences were observed in PCa-specific recurrence/progression between the younger and older patients, including after adjustment for clinical stage, PSA level, and Grade Group. CONCLUSIONS: In this study, the clinicopathological and molecular features of PCa diagnosed in young patients were comparable to those of PCa diagnosed in patients of screening age. Early-onset PCa cases were not enriched in any of the known molecular PCa subtypes in this small series.

Aberrant integrin αv and α5 expression in prostate adenocarcinomas and bone-metastases is consistent with a bone-colonizing phenotype.

BACKGROUND: Collaborative signaling between fibronectin-binding αv and α5 integrins has been implicated in the lethal dissemination of prostate cancer in the bone-metastatic niche, the major source of morbidity and mortality in the disease. METHODS: We assessed the frequency and pattern of expression of these integrins in primary high-grade adenocarcinomas and bone metastases compared to the physiological gland. Formalin-fixed paraffin-embedded (FFPE) radical prostatectomy (RP) samples (n=25) containing ≥ Gleason grade 4 cancer and decalcified surgical or diagnostic bone metastatic samples from 10 patients were stained for integrin αv (ITGAV) and integrin α5 (ITGA5) expression. Antibody optimization and antigen-retrieval was performed beforehand. RESULTS: ITGAV was exclusively expressed in the basal layer of physiological prostate glands whereas αv expression was invariably recapitulated in the malignant gland and bone metastases (100%) in multiple distinct patterns: epithelial membranous, basilar/luminal membranous, punctate cytoplasmic, intense foci as single cells or clusters, and rim stromal layers. The luminal/basilar layer of ITGAV expression was striking in cribriform carcinomas, suggestive of a role in molecular pathogenesis. ITGA5 infrequently highlighted the basal layer of the physiological gland, was absent in primary adenocarcinoma, but was expressed with ITGAV exclusively in bone metastases (71%). CONCLUSIONS: We conclude that ITGAV expression is aberrantly expressed in high frequency in high-grade prostatic adenocarcinomas in patterns suggestive of recapitulated basal cell functions, consistent with a stem-regulatory role that has been proposed. Co-expression and enrichment of αv and α5 in osseous metastases supports their proposed collaborative role in colonization of the bone microenvironment and as candidate targets for therapy.

Primary cutaneous cribriform apocrine carcinoma: Case report and literature review.

Primary cutaneous cribriform apocrine carcinoma is a rare but distinct variant of primary cutaneous apocrine carcinoma and it is considered a low grade malignancy. We herein present a case of primary cutaneous cribriform apocrine carcinoma at the neck of a 26-year-old female. The tumor features a relatively well-circumscribed border and multiple aggregations of mildly pleomorphic epithelial cells with large ovoid nuclei, small nucleoli and abundant eosinophilic cytoplasms. Cribriform and tubular structures are the major architectural patterns. The primary differential diagnosis is cutaneous metastasis from a cribriform visceral carcinoma; others include primary secretory carcinoma of the skin, adenoid cystic basal cell carcinoma and primary cutaneous adenoid cystic carcinoma.

GATA3 staining in primary cutaneous apocrine cribriform carcinoma: Usefulness to differentiate it from breast cancer metastasis.

BACKGROUND: Primary cutaneous apocrine cribriform carcinoma (PCACC) is a rare tumor, clinically appearing as a solitary nodule, mostly involving extremities of females and this lesion usually raises a differential diagnosis with metastatic cribriform carcinomas, especially breast cancer. OBJECTIVE: To study GATA3 expression in a series of 14 primary cutaneous cribriform carcinomas and to test its usefulness to differentiate this tumor from metastatic breast cancer. METHODS: We retrieved 14 cases with PCACC (each from a different patient) from the files of the authors. Cases were dated from 1994 to 2014. We also evaluated 6 cases of cutaneous breast cancer metastasis RESULTS: No PCACCs expressed GATA3. Breast cancer metastases expressed GATA3 in 100% of our studied cases. CONCLUSION: Even though GATA3 expression has been reported in many benign and malignant adnexal tumors (mostly of sebaceous, follicular, and apocrine differentiation), as well as in many other neoplasms, GATA3 staining to differentiate PCACC from skin breast cancer metastasis has a high negative predictive value. A positive GATA3 staining in this context should permit one to rule out PCACC with a high level of confidence.

Evaluation and comparison of radiologic-pathologic findings in invasive cribriform carcinoma of the breast.

BACKGROUND/AIM: This study aimed to report invasive cribriform carcinoma (ICC) with radiological and histopathologic correlations. MATERIALS AND METHODS: Seventy patients with ICC were classified into two groups; pure ICC patients and patients with >50% cribriform carcinoma component were included in group 1, while patients with <50% cribriform carcinoma component were included in group 2. All patients were reviewed according to American College of Radiology (ACR) breast imaging reporting and data system (BI-RADS) lexicon of mammography (MG), ultrasonography (US), and magnetic resonance imaging (MRI). One-way analysis of variance tests and t-tests were used for analysis. P < 0.05 was accepted as statistically significant. RESULTS: Eighteen patients were in group 1 and 52 were in group 2. All patients had MG and US, while 24 patients needed MRI. According to MG ACR BI-RADS lexicon evaluation, irregular shape, spiculated margin and indistinct margin, and high density were statistically significantly higher in group 2 than the other group (respectively P = 0.001, P = 0.001, and P= 0.04). Equal density was statistically significantly higher in group 1 than the other group (P = 0.008). According to US ACR BI-RADS lexicon evaluation, irregular shape, spiculated margins, angular margins, microlobulated margins, and nonparallel orientation were more common US findings in group 2 than the other group (respectively P = 0.001, P = 0.001, P = 0.003, P = 0.04, and P = 0.04). The rate of parallel orientation was higher in group 1 than the other group (P = 0.02). CONCLUSION: Few cases showed benign characteristics and most ICCs appear with typical features of malignancy. Radiologic features of ICC could be better understood and would be helpful for radiologists in diagnosing this rare type of malignancy.

An Updated Review of Cribriform Carcinomas with Emphasis on Histopathological Diagnosis and Prognostic Significance.

Cribriform is a histopathological term used to describe a neoplastic epithelial proliferation in the form of large nests perforated by many quite rounded different-sized spaces. This growth pattern may be seen in carcinomas arising in different organs, and shows important prognostic implications. Therefore, recent data in literature suggest that cribriform carcinoma is a histologically and clinically distinctive type of tumour that should be separated from other similar tumour types. In this article, the pathology of cribriform adenocarcinoma of the prostate, lung, breast, stomach, colon, thyroid, and skin is discussed with particular reference to morphologic and immunohistochemical features, differential diagnosis, and clinical behaviour.

Invasive cribriform carcinoma of the breast: a clinicopathological analysis of 12 cases with review of literature.

Invasive cribriform carcinoma (ICC) is a rare type of invasive breast cancer. We aim to investigate the clinicopathological features, immunophenotypes, diagnosis and differential diagnosis of ICC. Thus, clinicopathological data of 12 ICC patients were collected. All 12 cases were female, aged 38 to 75 years, with a median age of 53 years old. The maximum diameter of the tumor was 2 cm to 10 cm, in which the median tumor size was 2.54 cm in pure ICC and classical ICC. Microscopically, the cancer nests of ICC assumed an invasive, irregular island-shaped distribution, with an irregular mesh structure internally and fibrous reactions around most cancer nests. 67% (8/12) of cases were grade 1 and 33% (4/12) of cases were grade 2 tumors. Immunohistochemically, ER and PR were moderately to strongly positive with the positive tumor cell number accounting for 30% to 95% in all cases. HER-2 was negative in all cases except in one case which was positive (2+). Myoepithelial markers such as Calponin, p63, CK5/6 and CD10 were all negative in the cancer nests. 58% (7/12) of cases had a ki67 index of ≤ 14%. All follow-up patients were followed for 12 to 70 months (with a mean of 42 months), and were disease-free after treatment except for one patient whom we lost during the follow up. In conclusion, ICC, as a special type of breast cancer, has its unique clinicopathological and immunophenotypic characteristics, leading to a good prognosis.