Publications by authors named "Andres M Acosta"

30 Publications

  • Page 1 of 1

Grading Intraductal Carcinoma in Prostate Biopsies Changes Risk Categorization in a Small Subset of Cases.

Arch Pathol Lab Med 2021 Jul;145(7):782-784

Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

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http://dx.doi.org/10.5858/arpa.2020-0770-LEDOI Listing
July 2021

Comparative molecular analysis of testicular Leydig cell tumors demonstrates distinct subsets of neoplasms with aggressive histopathologic features.

Mod Pathol 2021 Jun 8. Epub 2021 Jun 8.

Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Testicular Leydig cell tumor (LCT), the most common sex-cord stromal tumor in men, represents a small fraction of all testicular tumors (~1 to 3%). Although most testicular LCTs are indolent and cured by radical orchiectomy, 5-10% have aggressive biology and metastatic potential. In primary LCTs, large size, cytologic atypia, necrosis, increased mitotic activity, and vascular invasion have been associated with clinically aggressive tumors. From a molecular perspective, the characteristics of aggressive LCTs and the differences between aggressive and nonaggressive LCTs remain largely unexplored. This study compares the genomic landscape of aggressive and nonaggressive testicular LCTs. Twenty-six cases were analyzed using next-generation DNA sequencing (NGS) and immunohistochemistry. Cases were classified as aggressive LCT if they met published criteria for malignancy in primary (i.e., testicular) tumors or if they had pathology-proven metastatic disease; otherwise, cases were considered nonaggressive. This multi-institutional series included 18 aggressive LCTs (14 primary/testicular, 4 metastatic) and 8 nonaggressive LCTs. Two cases (2/26, 8%; both aggressive LCTs) failed sequencing and had negative (i.e., uninformative) FH immunohistochemistry results. One additional primary aggressive LCT failed sequencing but had informative FH immunohistochemistry results. Combined NGS and immunohistochemical analysis demonstrated FH inactivation in 5/26 cases (19%). In addition, NGS demonstrated CTNNB1 mutations or biallelic APC inactivation in 9/23 cases (39%), copy number changes without recurrent mutations in 6/23 (26%) cases, and no alterations in 4/23 cases (17%). CTNNB1 mutations were present in both aggressive and nonaggressive LCTs. In contrast, FH inactivation and multiple copy number changes were only identified in aggressive LCTs. In conclusion, three distinct subgroups of aggressive LCTs were characterized by FH inactivation, Wnt pathway activation, and copy number changes without recurrent mutations, respectively. Nuclear translocation of β-catenin and Wnt pathway activation appear to be early driver events that provide an environment conducive for progression to aggressive biology in a subset of LCTs.
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http://dx.doi.org/10.1038/s41379-021-00845-3DOI Listing
June 2021

Primary Mucinous Adenocarcinoma of the Seminal Vesicle Associated with Intestinal Metaplasia: A Radiation-Induced Tumor?

Histopathology 2021 Jun 7. Epub 2021 Jun 7.

Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Primary adenocarcinoma of the seminal vesicle is very rare, with fewer than one hundred well-documented cases reported in the literature (1). These tumors have variable microscopic appearances, including cases with hobnail, polygonal and columnar neoplastic cells arranged in diverse architectural patterns (1). We recently received a radical cystoprostatectomy specimen from a 74-year-old patient with biopsy-proven muscle-invasive urothelial carcinoma.
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http://dx.doi.org/10.1111/his.14425DOI Listing
June 2021

Re-evaluating tumors of purported specialized prostatic stromal origin reveals molecular heterogeneity, including non-recurring gene fusions characteristic of uterine and soft tissue sarcoma subtypes.

Mod Pathol 2021 May 13. Epub 2021 May 13.

Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Tumors of purported specialized prostatic stromal origin comprise prostatic stromal sarcomas (PSS) and stromal tumors of uncertain malignant potential (STUMP). Prior studies have described their clinicopathologic characteristics, but the molecular features remain incompletely understood. Moreover, these neoplasms are morphologically heterogeneous and the lack of specific adjunctive markers of prostatic stromal lineage make precise definition more difficult, leading some to question whether they represent a specific tumor type. In this study, we used next-generation DNA and RNA sequencing to profile 25 primary prostatic mesenchymal neoplasms of possible specialized prostatic stromal origin, including cases originally diagnosed as PSS (11) and STUMP (14). Morphologically, the series comprised 20 cases with solid architecture (11 PSS and 9 STUMP) and 5 cases with phyllodes-like growth pattern (all STUMP). Combined DNA and RNA sequencing results demonstrated that 19/22 (86%) cases that underwent successful sequencing (either DNA or RNA) harbored pathogenic somatic variants. Except for TP53 alterations (6 cases), ATRX mutations (2 cases), and a few copy number variants (-13q, -14q, -16q and +8/8p), the findings were largely nonrecurrent. Eight gene rearrangements were found, and 4 (NAB2-STAT6, JAZF1-SUZ12, TPM3-NTRK1 and BCOR-MAML3) were useful for reclassification of the cases as specific entities. The present study shows that mesenchymal neoplasms of the prostate are morphologically and molecularly heterogeneous and include neoplasms that harbor genetic aberrations seen in specific mesenchymal tumors arising in other anatomic sites, including soft tissue and the uterus. These data suggest that tumors of purported specialized prostatic stromal origin may perhaps not represent a single diagnostic entity or specific disease group and that alternative diagnoses should be carefully considered.
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http://dx.doi.org/10.1038/s41379-021-00818-6DOI Listing
May 2021

SSX C-Terminus is a Useful Diagnostic Biomarker for Spermatocytic Tumour.

Histopathology 2021 May 7. Epub 2021 May 7.

Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.

Aims: Spermatocytic tumour (ST) is a rare testicular germ cell neoplasm that can be challenging to diagnose and for which there are few confirmatory biomarkers. Like normal spermatogonia, STs are known to express SSX proteins. Recently, a novel SSX antibody directed against the C-terminus (SSX_CT) of SSX1, SSX2 and SSX4, has emerged as a reliable biomarker for these SSX proteins and synovial sarcoma. However, SSX_CT immunostaining has not been demonstrated in ST. This study assessed the diagnostic utility of SSX_CT immunohistochemistry in ST and other tumors in the differential diagnosis with ST.

Methods And Results: SSX_CT, OCT3/4 and C-KIT immunohistochemistry was performed on 15 STs, 38 seminomas, 13 embryonal carcinomas, 12 yolk sac tumours, 6 choriocarcinomas, 4 teratomas, 7 Sertoli cell tumors, and 6 lymphomas. Staining was scored as negative, rare, focal or diffuse. SSX_CT was positive in all (15/15) STs; diffusely in 14/15. SSX_CT was positive in 22/38 (58%) seminomas; however, only 2 cases showed diffuse expression. All other tumours were SSX_CT negative. OCT3/4 was negative in all STs, but positive in all seminomas and embryonal carcinomas. C-KIT was frequently positive in both ST (12/15; 80%) and seminoma (33/38; 87%). All other tumours were negative for OCT3/4 and C-KIT.

Conclusions: SSX_CT is a valuable and highly sensitive biomarker that supports the diagnosis of ST. Diffuse expression, observed in 93% of STs (compared to 6% of seminomas), is also highly specific for ST. Nevertheless, SSX_CT is best used in combination with OCT3/4 when ST is in the differential diagnosis.
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http://dx.doi.org/10.1111/his.14398DOI Listing
May 2021

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

Histopathology 2021 May 16;78(6):857-870. Epub 2021 Mar 16.

Department of Pathology, Genitourinary Pathology Division, Brigham and Women's Hospital, Boston, MA, USA.

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.
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http://dx.doi.org/10.1111/his.14315DOI Listing
May 2021

p-120 Catenin is a Useful Diagnostic Biomarker for Distinguishing Plasmacytoid and Sarcomatoid Variants From Conventional Urothelial Carcinoma.

Arch Pathol Lab Med 2020 Nov 25. Epub 2020 Nov 25.

From the Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (Acosta, Barletta, Schnitt, Hirsch).

Context.—: Plasmacytoid urothelial carcinoma (PC-UC) is an aggressive variant of urothelial carcinoma (UC), characterized by loss of E-cadherin (E-Cad)-mediated intercellular adhesion. Loss of E-Cad by immunohistochemistry can help diagnosis PC-UC; however, sensitivity is limited. Expression of other cadherin-catenin adhesion complex members, that is, p-120 catenin (p-120) and β-catenin (B-Cat), which are diagnostically useful for lobular breast carcinoma, remains unknown in UC.

Objective.—: To determine the utility of p-120 and B-Cat in conventional and variant UC.

Design.—: E-cadherin, B-Cat, and p-120 immunohistochemistry was performed in 25 conventional UCs and 33 variant UCs, including 22 PC-UCs, 6 sarcomatoid UCs (SUCs), and 5 micropapillary UCs. Membranous staining for all biomarkers was considered normal; however, any cytoplasmic staining or an absence of staining was considered diagnostically abnormal. Next-generation sequencing was performed on 8 PC-UC cases.

Results.—: E-cadherin, B-Cat, and p-120 showed membranous staining in all conventional and micropapillary UCs. In contrast, most PC-UCs were negative for E-Cad (17 of 22; 77%) with an additional 2 of 22 cases (9%) showing cytoplasmic with partial membranous staining. p-120 catenin demonstrated cytoplasmic or negative staining in 21 of 22 cases (95%). Most SUCs showed an absence of E-Cad (5 of 6; 83%) and cytoplasmic or negative p-120 in 5 of 6 cases (83%). Staining for B-Cat was also abnormal in a subset of PC-UCs and SUCs. Five PC-UC cases that harbored CDH1 gene variants were p-120 cytoplasmic positive.

Conclusions.—: p-120 catenin is a useful adjunct biomarker to E-Cad in the clinically important distinction of PC-UC and SUC from conventional UC. In particular, the combination of cytoplasmic p-120 and loss of E-Cad is strongly supportive of PC-UC and SUC.
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http://dx.doi.org/10.5858/arpa.2020-0262-OADOI Listing
November 2020

Pseudosarcomatous myofibroblastic proliferations of the urinary bladder are neoplasms characterized by recurrent FN1-ALK fusions.

Mod Pathol 2021 02 9;34(2):469-477. Epub 2020 Sep 9.

Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Pseudosarcomatous myofibroblastic proliferation is a descriptive term that designates a group of clinically indolent genitourinary lesions that most commonly arise in the urinary bladder. Given that pseudosarcomatous myofibroblastic proliferation may show morphologic overlap with inflammatory myofibroblastic tumor, the relationship, if any, between the two entities has been unclear. Moreover, pseudosarcomatous myofibroblastic proliferations are known to be positive for ALK immunohistochemistry in a subset of cases, although an inconsistent association with ALK rearrangement (ranging from 0 to 60%) has been reported. The objectives of this study were to determine the frequency of ALK rearrangement and to identify fusion partners using fluorescence in situ hybridization (FISH) and targeted RNA sequencing studies in a contemporary series of 30 pseudosarcomatous myofibroblastic proliferations of the urinary bladder, as well as to investigate ROS1 status by immunohistochemistry. ALK immunohistochemistry was positive in 70% (21/30) of pseudosarcomatous myofibroblastic proliferations; ROS1 immunohistochemistry was consistently negative (0/28). ALK rearrangements were detected by FISH in 86% (18/21) of cases, correlating with ALK immunohistochemical positivity in all but 3 cases. Of eight cases confirmed to be ALK rearranged by FISH, targeted RNA-sequencing detected FN1-ALK fusions in seven (88%) cases, which involved exons 20-26 of FN1 (5') and exon 18-19 of ALK (3'). In conclusion, ALK rearrangements are frequent in pseudosarcomatous myofibroblastic proliferations, typically involving exon 19, and FN1 appears to be a consistent fusion partner. Given the significant clinicopathologic differences between inflammatory myofibroblastic tumor and pseudosarcomatous myofibroblastic proliferation, our findings provide further support for classification of pseudosarcomatous myofibroblastic proliferation as a distinct clinicopathologic entity, and propose the alternate terminology "pseudosarcomatous myofibroblastic neoplasm of the genitourinary tract."
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http://dx.doi.org/10.1038/s41379-020-00670-0DOI Listing
February 2021

Intestinal metaplasia of the urinary tract harbors potentially oncogenic genetic variants.

Mod Pathol 2021 02 28;34(2):457-468. Epub 2020 Aug 28.

Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

In the urinary tract, there is an uncertain relationship between intestinal metaplasia (IM), primary adenocarcinoma, and urothelial carcinoma. Although IM is usually found adjacent to concurrent urothelial carcinoma or adenocarcinoma, small retrospective series have shown that most bladder biopsies with only IM do not subsequently develop cancer. However, IM with dysplasia does seem to be associated with a higher risk of concurrent malignancy or progressing to cancer. Since the molecular landscape of these lesions has remained largely unexplored, there are significant uncertainties about the oncogenic potential of IM in the bladder and urethra. This study investigated the presence of potentially oncogenic genetic variants in cases of IM with and without dysplasia. Twenty-three (23) cases of IM (3 urethra, 20 bladder) were sequenced using a solid tumor next-generation sequencing panel. Of these, five contained IM with high-grade dysplasia (including a case with paired IM-adenocarcinoma and another with paired IM-urothelial carcinoma) and 18 lacked dysplasia. Oncogenic genetic variants were found in all cases of IM with high-grade dysplasia and in five non-dysplastic IM cases, including mutations and copy number variants commonly seen in primary adenocarcinoma of the bladder and urothelial carcinoma. This study demonstrates that IM can harbor potentially oncogenic genetic variants, suggesting that it might represent a cancer precursor or a marker of increased cancer risk in a subset of cases.
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http://dx.doi.org/10.1038/s41379-020-00655-zDOI Listing
February 2021

Malignant tumours of the uterus and ovaries with Mullerian and germ cell or trophoblastic components have a somatic origin and are characterised by genomic instability.

Histopathology 2020 Nov 22;77(5):788-797. Epub 2020 Sep 22.

Women's and Perinatal Pathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Aims: Tumours of the female genital tract with a combination of malignant Mullerian and germ cell or trophoblastic tumour (MMGC/T) components are usually diagnosed in postmenopausal women, and pursue an aggressive clinical course characterised by poor response to therapy and early relapses. These clinical features suggest that MMGC/T are somatic in origin, but objective molecular data to support this interpretation are lacking. This study evaluates the molecular features of nine MMGC/T, including seven tumours containing yolk sac tumour (YST), one tumour containing choriocarcinoma and one tumour containing epithelioid trophoblastic tumour. The objectives were to: (i) investigate whether MMGC/T show a distinct genetic profile and (ii) explore the relationship between the different histological components.

Methods And Results: Next-generation sequencing of paired samples demonstrated that the mutational profile of the Mullerian and non-Mullerian components of the tumour were almost identical in all cases. Moreover, the driver mutations identified were those expected in the specific subtype of Mullerian component present in each case. In contrast, variants expected in postpubertal germ cell tumours and gestational trophoblastic tumours were not identified, and FISH for i(12p) was negative in all cases tested. In this study, mismatch repair-proficient MMGC/T (eight of nine) were characterised by a complex copy-number variant profile, including numerous focal, regional, arm-level and chromosome-level events.

Conclusions: Comparison of paired samples supports that the YST and trophoblastic tumour components of MMGC/T have a somatic origin and often show numerous copy-number variants, suggestive of underlying genomic instability.
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http://dx.doi.org/10.1111/his.14188DOI Listing
November 2020

Volume of Gleason pattern 4 stratifies risk of metastasis and death in patients with Gleason score 3+5=8/5+3=8 positive prostate core biopsies.

Hum Pathol 2020 05 11;99:62-74. Epub 2020 Mar 11.

Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115 USA. Electronic address:

Implementation of Grade Groups (GrGrs) has been widely accepted for reporting prostate cancer grade since the 2014 International Society of Urological Pathology consensus meeting. Despite their undisputed value for risk stratification, some GrGr are, a priori, quite heterogeneous in that they contain multiple Gleason patterns (GPs). In this regard, the prognostic significance of GP5 in biopsies with highest GrGr4 is uncertain and evaluated in this study. A search of all core biopsies positive for prostate cancer reviewed after 2005 was performed, and 71 cases with highest GrGr4 containing GP5 (i.e., 3 + 5 = 8 or 5 + 3 = 8; referred to as GrGr4/GP5pos) eligible for inclusion were identified. In addition, 95 core biopsy cases with highest GrGr4 and no GP5 (i.e, 4 + 4 = 8; referred to as GrGr4/GP5neg) were selected for comparison. Multiple pathologic parameters, including volume and amount of GP4, and clinical variables were collected to evaluate the influence of GP5 on disease recurrence, development of metastases, and disease-specific death. GrGr4/GP5pos cases did not show, as a group, statistically significant differences in prostatectomy findings, disease recurrence, metastases, and disease-specific mortality when compared with GrGr4/GP5neg cases. In addition, the risk of all outcomes evaluated in the study did not differ between the whole GrGr4/GP5pos and GrGr4/GP5neg groups. However, Kaplan-Meier analysis found that GrGr4/GP5pos cases with a significant amount of GP4 did show a higher risk of prostate cancer-specific death as well as bone and visceral metastases. Univariate Cox regression demonstrated that preoperative prostate specific antigen (PSA), total number of positive cores, and global GrGr5 were also associated with a higher chance of disease-specific death. In a multivariate model, only global GrGr5 and PSA >20 ng/dL remained statistically significant. This study suggests that the mere presence of GP5 in core biopsies with highest GrGr4 disease may not portend a worse prognosis. In these cases, accounting for the case-wide volume of GP4 by reporting a global GrGr appears to be more relevant as it identifies a subset of GrGr4/GP5pos patients with global GrGr5 who have a higher risk of metastases and prostate cancer-specific mortality.
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http://dx.doi.org/10.1016/j.humpath.2020.03.001DOI Listing
May 2020

Association of High miR-182 Levels with Low-Risk Prostate Cancer.

Am J Pathol 2019 04 29;189(4):911-923. Epub 2019 Jan 29.

Department of Pathology, College of Medicine, University of Illinois at Chicago, Chicago. Electronic address:

A subset of men with prostate cancer develops aggressive disease. We sought to determine whether miR-182, an miRNA with reported oncogenic functions in the prostate, is associated with biochemical recurrence and aggressive disease. Prostate epithelial miR-182 expression was quantified via in situ hybridization of two prostate tissue microarrays and by laser-capture microdissection of prostate epithelium. miR-182 was significantly higher in cancer epithelium than adjacent benign epithelium (P < 0.0001). The ratio of cancer to benign miR-182 expression per patient was inversely associated with recurrence in a multivariate logistic regression model (odds ratio = 0.18; 95% CI, 0.03-0.89; P = 0.044). Correlation of miR-182 with mRNA expression in laser-capture microdissected benign prostate epithelium was used to predict prostatic miR-182 targets. Genes that were negatively correlated with miR-182 were enriched for its predicted targets and for genes previously identified as up-regulated in prostate cancer metastases. miR-182 expression was also negatively correlated with genes previously identified as up-regulated in primary prostate tumors from African American patients, who are at an increased risk of developing aggressive prostate cancer. Taken together, these results suggest that although miR-182 is expressed at higher levels in localized prostate cancer, its levels are lower in aggressive cancers, suggesting a biphasic role for this miRNA that may be exploited for prognostic and/or therapeutic purposes to reduce prostate cancer progression.
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http://dx.doi.org/10.1016/j.ajpath.2018.12.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446228PMC
April 2019

Hepatoid Carcinoma of the Ovary: Clinical, Histopathologic, and Immunophenotypic Features.

Arch Pathol Lab Med 2019 07 10;143(7):883-889. Epub 2019 Jan 10.

From the University of Illinois at Chicago (Dr Acosta); the Chicago Medical School of Rosalind Franklin University of Medicine and Science, North Chicago, Illinois (Dr Pins); and the Advocate Lutheran General Hospital and the James R. & Helen D. Russell Institute for Research & Innovation, Park Ridge, Illinois (Dr Pins).

Hepatoid carcinoma of the ovary (HCO) is a rare malignant tumor of uncertain histogenesis that was first described by Ishikura and Scully in the late 1980s. Unlike hepatoid yolk sac tumor (HYST), one of its main differential diagnoses, HCO usually presents in perimenopausal and postmenopausal women without gonadal dysgenesis. Most cases show advanced local disease at initial presentation, with diffuse intraperitoneal dissemination. Despite aggressive treatment, including surgery and adjuvant chemotherapy, 61.5% of patients either die of the disease (11 of 26; 42.3%) or are alive with recurrent or residual disease (5 of 26; 19.2%) after a median follow-up of 11.5 months (range, 1-60 months). Most HCOs are solid, with high-grade histology, significant nuclear pleomorphism, scattered giant cells, and a high mitotic index. Their immunophenotype is defined by the expression of broad-spectrum cytokeratins, α-fetoprotein, and hepatocellular antigens with absence of sex cord and germ cell markers. Although immunohistochemistry can be very helpful to distinguish between sex cord-stromal tumors and HCO, differentiation of the latter from HYST, metastatic hepatocellular carcinoma, and metastatic gastrointestinal tumors with hepatoid phenotype requires integration of clinical, radiologic, and pathologic information.
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http://dx.doi.org/10.5858/arpa.2017-0485-RSDOI Listing
July 2019

Comparison of prostatic adenocarcinoma Gleason 5 and intraductal carcinoma of the prostate with tumor necrosis. A morphometric study.

Pathol Res Pract 2018 Oct 29;214(10):1681-1685. Epub 2018 Aug 29.

Department of Pathology, University of Illinois at Chicago, Chicago, IL, United States. Electronic address:

Intraductal carcinoma of the prostate(IDCP) is defined as a solid or cribriform neoplastic growth confined to ducts and acini, with preservation of the basal cell layer. Since IDCP can often present tumor necrosis (TN), it should be distinguished from Gleason 5 (GP5) invasive adenocarcinoma for staging and clinical purposes. In the present study we reviewed 344 radical prostatectomies performed at our institution and selected all cases with either >5% GP5 or IDCP for assessment of TN on histology slides (n = 59). A total of 19 cases with TN were identified, and morphology, size, location, and histoarchitecture of the lesions with TN were recorded. Subsequently, the corresponding sections were stained with a basal cell immunomarker (P63), and lesions with TN were assigned to IDCP or invasive carcinoma GP5 for comparison. Our results show that a branched shape and size 501-1000 μm are more common in IDCP, while a size >1000 μm and location within 1 mm of the periprostatic soft tissue are significantly more prevalent in invasive adenocarcinoma GP5. These features, however, usually cannot be assessed in core biopsies. In this setting, the utilization of immunohistochemistry is warranted to differentiate IDCP and GP5 with necrosis.
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http://dx.doi.org/10.1016/j.prp.2018.08.030DOI Listing
October 2018

Sebaceous carcinoma of the breast in a patient with a pathogenic BRCA2 (886delGT) mutation - focus on histopathologic and immunohistochemical features.

APMIS 2018 Apr;126(4):353-356

Department of Pathology, Chicago Medical School, North Chicago, IL, USA.

Sebaceous carcinoma of the breast (SCB) is a rare variant of ductal carcinoma arising within the mammary gland and containing at least 50% of malignant cells with sebaceous differentiation. Only 11 cases that adjust to the criteria delineated in the WHO classification have been published in the English literature, to the best of our knowledge. Here, we present the first SCB arising in the context of a deleterious BRCA2 mutation, focusing on the histopathologic and immunohistochemical features of this exceedingly rare tumor.
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http://dx.doi.org/10.1111/apm.12826DOI Listing
April 2018

Tumor necrosis in radical prostatectomies with high-grade prostate cancer is associated with multiple poor prognostic features and a high prevalence of residual disease.

Hum Pathol 2018 05 24;75:1-9. Epub 2017 Nov 24.

Department of Pathology, University of Illinois at Chicago, Chicago, IL 60612. Electronic address:

The Gleason grading system and the recently defined Grade Groups are strong, well-established predictors of outcome in prostate cancer. Each Gleason score, however, is the result of a sum of categories (Gleason patterns or GPs) that are intrinsically heterogeneous, as each individual pattern encompasses several tumor morphologies. Although the prognostic value of specific morphologic components of GP4 has recently been demonstrated, the significance of the different patterns of GP5 is largely unknown. We reviewed 344 consecutive prostatectomies performed at the Hospital of the University of Illinois at Chicago between 2011 and 2016 and selected 56 cases with primary or secondary GP5 with archival material available for review. Subsequently, we sorted the cases according to the presence or absence of tumor necrosis in invasive adenocarcinoma GP5-designated G5 (+N) and G5 (-N), respectively-for comparison of histopathologic and clinical characteristics. The GP5 (+N) group demonstrated higher prevalence of biochemical recurrence (P=.0006) and seminal vesicle invasion (P=.02), with a trend toward a higher frequency of lymph node metastases (P=.07) and multifocal surgical margin involvement (P=.09). Also, G5 (+N) patients showed higher preoperative prostate-specific antigen values (P=.005) and a larger percentage of submitted tissue involved by tumor (P<.0001). Our results show that GP5 with tumor necrosis is associated with poor prognostic histopathologic features and high rates of residual disease after prostatectomy.
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http://dx.doi.org/10.1016/j.humpath.2017.11.015DOI Listing
May 2018

Granulomas within renal epithelial neoplasms in patients with sarcoidosis: A causal association?

Pathol Res Pract 2017 Nov 23;213(11):1431-1434. Epub 2017 Jul 23.

Surgical Pathology Division, Department of Pathology, University of Illinois at Chicago, 840 S. Wood St., Suite 130 CSN, Chicago, IL, 60612, United States; Hematologic Pathology Division, Department of Pathology, University of Illinois at Chicago, 840 S. Wood St., Suite 130 CSN, Chicago, IL, 60612, United States.

Sarcoidosis is a chronic granulomatous disease that can involve virtually every organ system, but most commonly presents as lung, skin, or lymph node disease. Although kidney involvement is usually clinically silent, granulomatous interstitial nephritis - the hallmark of renal sarcoidosis - can lead to functional impairment and organ failure. Also, recent studies have suggested an association between sarcoidosis and an increased risk of developing kidney tumors. While a sarcoid-like granulomatous reaction (SLGR) to renal epithelial neoplasms in patients without sarcoidosis has been well documented, direct involvement of the tumor parenchyma by sarcoidosis has been reported only rarely. Here we present two renal epithelial tumors directly involved by sarcoidosis with a common pattern of distribution of non-caseating granulomas.
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http://dx.doi.org/10.1016/j.prp.2017.07.021DOI Listing
November 2017

Metastatic intestinal adenocarcinoma to a lymph node involved by follicular lymphoma: The importance of looking beyond the apparent.

Pathol Res Pract 2017 Jun 5;213(6):713-716. Epub 2016 Dec 5.

Chicago Medical School, United States; Advocate Lutheran General Hospital, 1775 Dempster St, S/F Building, Park Ridge, IL, 60068, United States. Electronic address:

Composite tumors consisting of follicular lymphoma (FL) and colorectal or small intestinal adenocarcinoma are exceedingly rare, with only four cases published in the literature, to the best of our knowledge. While in most of these cases the clinical prognosis seems to be determined by the adenocarcinoma, at least one patient has shown rapid and aggressive progression of the FL. Here we report on a 62 year-old male with colonic adenocarcinoma metastatic to a retroperitoneal lymph node involved by FL, which illustrates the importance of carefully examining the histomorphology of lymphoid elements in surgical specimens.
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http://dx.doi.org/10.1016/j.prp.2016.12.002DOI Listing
June 2017

The Development of Prostate Adenocarcinoma in a Transgender Male to Female Patient: Could Estrogen Therapy Have Played a Role?

Prostate 2017 Jun 13;77(8):824-828. Epub 2017 Feb 13.

Department of Urology, University of Illinois at Chicago, Chicago, Illinois.

Background: Prostate adenocarcinoma (PCa) is a rare diagnosis in the male to female transgender (MtFT) population with only a few case reports published in the current medical literature. Long standing beliefs of androgen suppression conferring a protective effect against prostate cancer development have been challenged by the literature citing adenocarcinoma development in the prostate of rodent models following combined estrogen and testosterone treatment.

Materials And Methods: We herein present a MtFT patient who presented with high grade PCa following 20 years of exogenous estrogen therapy.

Results: Immunohistochemical (IHC) localization of estrogen receptor alpha (ER-α) and progesterone receptor (PR) demonstrated positive staining in stromal cells; while, androgen receptor (AR) demonstrated positive staining in malignant glands and weak scattered staining in adjacent stroma.

Conclusion: This pattern of staining raises concern for a possible contributing role of exogenous estrogen therapy in tumorigenesis. As awareness of gender dysphoria and acceptance of gender reassignment surgery has seen a recent increase, the unique needs of this population must be recognized. Prostate 77:824-828, 2017. © 2017 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/pros.23322DOI Listing
June 2017

Tracing the footprints: A case of chronic meningitis with unusual mononuclear cells in the cerebrospinal fluid.

Diagn Cytopathol 2017 May 11;45(5):433-435. Epub 2017 Feb 11.

Department of Pathology, College of Medicine, University of Illinois Hospital & Health Sciences System, Chicago, Illinois.

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http://dx.doi.org/10.1002/dc.23684DOI Listing
May 2017

microRNAs and DICER1 are regulated by 1,25-dihydroxyvitamin D in prostate stroma.

J Steroid Biochem Mol Biol 2017 03 12;167:192-202. Epub 2017 Jan 12.

Department of Pathology, University of Illinois at Chicago, Chicago, IL, United States; University of Illinois Cancer Center, Chicago, IL, United States. Electronic address:

Vitamin D deficiency increases the risk of lethal prostate adenocarcinomas (PCa) and the majority of older men are deficient. Although PCa arises from the epithelium, the surrounding stroma has hormonal regulatory control over the epithelium and contributes to carcinogenesis. Herein, we describe regulation of microRNAs (miRs) by the active hormone dihydroxyvitamin D (1,25(OH)D) in human prostate stroma. 1,25(OH)D binds the vitamin D receptor (VDR) transcription factor to regulate gene expression, including miRs, which have emerged as potent regulators of protein expression. 1,25(OH)D-regulated miRs were identified by profiling in primary human prostatic stromal cells (PrS) and three miRs, miR-126-3p, miR 154-5p and miR-21-5p were subsequently validated in laser-capture micro-dissected prostate stromal tissue from a vitamin D3 clinical trial (N=45). Regulation of these miRs by 1,25(OH)D was VDR-dependent. Network analysis of known and putative mRNA targets of these miRs was enriched with cancer and inflammation pathways, consistent with known roles of stroma and of vitamin D in carcinogenesis. Expression of the miR processing ribonuclease, DICER1, positively correlated with vitamin D metabolite levels in the clinical trial specimens. High epithelial/stromal ratios of DICER1 were significantly associated biochemical recurrence (OR 3.1, p=0.03) in a tissue microarray of 170 matched PCa patients. In summary, these results underscore the role of the prostate stroma in regulating responses to the hormone 1,25(OH)D and identified miRs and DICER1 as being regulated in human prostate stroma. Regulation of stromal DICER1 by 1,25(OH)D may also have clinical relevance in protection against aggressive PCa.
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http://dx.doi.org/10.1016/j.jsbmb.2017.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5304339PMC
March 2017

Ductal Spread Versus High-Grade Prostatic Intraepithelial Neoplasia: A Diagnostic Pitfall.

Int J Surg Pathol 2016 Dec 7;24(8):718-719. Epub 2016 Sep 7.

University of Illinois at Chicago, IL, USA.

Ductal spread (DS) of acinar adenocarcinoma of the prostate can lead to an incomplete replacement of the benign epithelium by cancer cells, resulting in a lesion that can be indistinguishable from high-grade prostatic intraepithelial neoplasia (HGPIN). Kovi and colleagues demonstrated 30 years ago that there is a significant association between the presence of DS and local extent of invasive adenocarcinoma, making the distinction between DS and HGPIN clinically relevant. However, despite the existence of certain morphologic features that are suggestive of DS, a definitive differentiation between the aforementioned lesions cannot always be attained.
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http://dx.doi.org/10.1177/1066896916668639DOI Listing
December 2016

Primary Biliary Mixed Adenoneuroendocrine Carcinoma (MANEC): A Short Review.

Arch Pathol Lab Med 2016 Oct;140(10):1157-62

From the Department of Pathology, University of Illinois at Chicago Hospital and Health Sciences System.

Mixed adenoneuroendocrine carcinomas (MANECs) are composite neoplasms with areas of adenocarcinoma or squamous cell carcinoma intermingled with neuroendocrine carcinoma or neuroendocrine tumor, each composing at least 30% of the neoplasm. MANECs are very infrequent overall, and they are more commonly diagnosed in the appendix, colon, and stomach. Biliary MANECs are particularly rare, and their histogenesis is debated because neuroendocrine cells are seldom identified in the normal biliary tract. They can show one of the 3 different architectural patterns described in Lewin's original classification: collision tumors, combined lesions, or amphicrine neoplasms. The neuroendocrine component is usually of a high grade, with small or large cell cytomorphology, whereas the adenocarcinoma component is either an intestinal or biliary type. Clinical presentation is characterized by locally advanced disease at the time of initial diagnosis. Recent studies suggest that treatment should be guided by the most aggressive histologic component.
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http://dx.doi.org/10.5858/arpa.2015-0102-RSDOI Listing
October 2016

Poorly Differentiated Esophageal Adenocarcinoma Metastatic to a Well-differentiated Lung Adenocarcinoma: When Morphology and Immunohistochemistry Prevail Over Molecular Results.

Appl Immunohistochem Mol Morphol 2017 08;25(7):e58-e60

*Department of Pathology, University of Illinois at Chicago, Chicago †Chicago Medical School, Advocate Lutheran General Hospital Park Ridge, IL.

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http://dx.doi.org/10.1097/PAI.0000000000000419DOI Listing
August 2017

Primary Neuroendocrine Tumors of the Ureter: A Short Review.

Arch Pathol Lab Med 2016 Jul;140(7):714-7

From Anatomic/Clinical Pathology (Dr Acosta) and Transdisciplinary Pathology (Dr Kajdacsy-Balla), University of Illinois at Chicago Hospital and Health Sciences System, Chicago.

Neuroendocrine tumors represent 0.05% of urinary tract malignancies, and most originate in the bladder. Their pathogenesis is debated, since ureters are thought to lack neuroendocrine cells. Morphologically, most ureteral neuroendocrine tumors demonstrate the typical small cell neuroendocrine appearance, are immunohistochemically positive for synaptophysin/chromogranin A/CD56, and show electron-dense granules by electron microscopy. Clinical presentation is similar to that of other more common ureteral neoplasms. Prognosis is usually dismal, but a multimodal treatment approach including platinum-based adjuvant or neoadjuvant chemotherapy seems to be beneficial.
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http://dx.doi.org/10.5858/arpa.2015-0106-RSDOI Listing
July 2016

Post-transplant extranodal NK/T-cell lymphoma, nasal type with cutaneous and pulmonary involvement.

Pathology 2016 Jun 26;48(4):380-3. Epub 2016 Apr 26.

Department of Pathology, John H. Stroger Jr Hospital of Cook County (CCHS), Chicago, IL, United States.

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http://dx.doi.org/10.1016/j.pathol.2016.03.011DOI Listing
June 2016

The Fragile Intraductal Lesions of the Prostate.

Int J Surg Pathol 2016 Sep 10;24(6):535-6. Epub 2016 Apr 10.

Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA.

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http://dx.doi.org/10.1177/1066896916642291DOI Listing
September 2016

Identification of miracidia of Schistosoma haematobium in a bladder wash sample.

Diagn Cytopathol 2016 May 12;44(5):413-5. Epub 2016 Mar 12.

Department of Pathology, John H. Stroger, Jr. Hospital of Cook County (CCHHS), Chicago, Illinois.

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http://dx.doi.org/10.1002/dc.23464DOI Listing
May 2016

Papillary thyroid carcinoma with extensive squamous dedifferentiation metastatic to the lung: BRAF mutational analysis as a useful tool to rule out tumor to tumor metastasis.

Virchows Arch 2016 Feb 31;468(2):239-42. Epub 2015 Oct 31.

Department of Pathology, Chicago Medical School, HSB Room 1.652, North Chicago, IL, 60064, USA.

Tumors containing elements of both papillary thyroid carcinoma (PTC) and squamous cell carcinoma (SCC) are rare but well documented. When they present initially as metastatic disease in an organ that can harbor a primary SCC, the possibility of a tumor to tumor metastasis (TTM) must be considered. The aim of this case study is to illustrate how BRAF mutational analysis can be used to help differentiate between these two diagnoses. We report a 63-year-old male with a longstanding history of PTC metastatic to the brain and lymph nodes who presented to our institution with a right lower lobe lung mass after a 2-year recurrence-free interval. Histopathologic and immunohistochemical analysis revealed a composite neoplasm with distinct elements of both PTC and SCC. We performed BRAF (V600E) (c.1799 T > A) mutational analysis to help elucidate the origin of each component. This is the first time that BRAF sequencing has been used to discriminate between dedifferentiated PTC and TTM, to the best of our knowledge. In the context of metastatic PTC with SCC dedifferentiation, the presence of the identical BRAF (V600E) (c.1799 T > A) mutation in both components might help rule out tumor to tumor metastasis.
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http://dx.doi.org/10.1007/s00428-015-1875-8DOI Listing
February 2016