Publications by authors named "Jae Y Ro"

268 Publications

Biopsy-Integrated 3D Magnetic Resonance Imaging Modeling of Prostate Cancer and Its Application for Gleason Grade and Tumor Laterality Assessment.

Arch Pathol Lab Med 2022 May 5. Epub 2022 May 5.

Department of Radiology (Park), Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Context.—: Grade Group assessed using Gleason combined score and tumor extent is a main determinant for risk stratification and therapeutic planning of prostate cancer.

Objective.—: To develop a 3-dimensional magnetic resonance imaging (MRI) model regarding Grade Group and tumor extent in collaboration with uroradiologists and uropathologists for optimal treatment planning for prostate cancer.

Design.—: We studied the data from 83 patients with prostate cancer who underwent multiparametric MRI and subsequent MRI-transrectal ultrasound fusion biopsy and radical prostatectomy. A 3-dimensional MRI model was constructed by integrating topographic information of MRI-based segmented lesions, biopsy paths, and histopathologic information of biopsy specimens. The multiparametric MRI-integrated Grade Group and laterality were assessed by using the 3-dimensional MRI model and compared with the radical prostatectomy specimen.

Results.—: The MRI-defined index tumor was concordant with radical prostatectomy in 94.7% (72 of 76) of cases. The multiparametric MRI-integrated Grade Group revealed the highest agreement (weighted κ, 0.545) and a significantly higher concordance rate (57.9%) than the targeted (47.8%, P = .008) and systematic (39.4%, P = .01) biopsies. The multiparametric MRI-integrated Grade Group showed significantly less downgrading rates than the combined biopsy (P = .001), without significant differences in upgrading rate (P = .06). The 3-dimensional multiparametric MRI model estimated tumor laterality in 66.2% (55 of 83) of cases, and contralateral clinically significant cancer was missed in 9.6% (8 of 83) of cases. The tumor length measured by multiparametric MRI best correlated with radical prostatectomy as compared with the biopsy-defined length.

Conclusions.—: The 3-dimensional model incorporating MRI and MRI-transrectal ultrasound fusion biopsy information easily recognized the spatial distribution of MRI-visible and MRI-nonvisible cancer and provided better Grade Group correlation with radical prostatectomy specimens but still requires validation.
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http://dx.doi.org/10.5858/arpa.2021-0256-OADOI Listing
May 2022

Superficial CD34-positive fibroblastic tumor (SCPFT): A review of pathological and clinical features.

Ann Diagn Pathol 2022 Jun 24;58:151937. Epub 2022 Mar 24.

Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Weill Medical College of Cornell University, Houston, TX, United States of America. Electronic address:

Superficial CD34-positive fibroblastic tumor (SCPFT) is a recently described rare mesenchymal tumor of borderline malignancy. It generally involves superficial soft tissue, with a predilection to the lower extremities. Microscopically this tumor is characterized by a fascicular and storiform growth pattern, spindled to epithelioid cells, nuclear atypia with pleomorphism, and eosinophilic granular, and fibrillar to glassy cytoplasm. Strong diffuse immunoreactivity for CD34 is very characteristic of this entity. Due to under-recognition, this tumor is generally underreported. Additionally, cases of recurrence are rarely reported in the literature. We will comprehensively review the English language literature on all reported cases of SCPFT, with emphasis on recurrence.
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http://dx.doi.org/10.1016/j.anndiagpath.2022.151937DOI Listing
June 2022

Mediastinal neuroblastoma, ganglioneuroblastoma, and ganglioneuroma: Pathology review and diagnostic approach.

Semin Diagn Pathol 2022 Mar 15;39(2):120-130. Epub 2021 Jun 15.

Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Weill Medical College of Cornell University, Houston, TX, 77030, USA.

Neuroblastic tumors are a group of tumors of the sympathetic ganglia and adrenal medulla that derive from primordial neural crest cells. These tumors include neuroblastoma, intermixed ganglioneuroblastoma, nodular ganglioneuroblastoma, and ganglioneuroma. Neuroblastomas are the most common extracranial solid tumor arising in childhood and may occur in different anatomic sites. Neuroblastic tumors are common mesenchymal tumors of the mediastinum. Herein, we describe advances in our understanding of neuroblastic tumor biology. Pathologists should be aware of diagnostic challenges associated with these tumors to ensure correct histologic diagnosis and appropriate clinical management. We describe updated mediastinal neuroblastic tumor pathology, focusing on morphological, immunohistochemical, and molecular features and differential diagnoses.
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http://dx.doi.org/10.1053/j.semdp.2021.06.007DOI Listing
March 2022

Mesenchymal Tumors of the Mediastinum: An Update on Diagnostic Approach.

Adv Anat Pathol 2021 Sep;28(5):351-381

Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Weill Medical College of Cornell University, Houston, TX.

Mesenchymal tumors of the mediastinum are a heterogenous group of rare tumors with divergent lineages. Mediastinal mesenchymal tumors are diagnostically challenging due to their diversity and morphologic overlap with nonmesenchymal lesions arising in the mediastinum. Accurate histologic diagnosis is critical for appropriate patient management and prognostication. Many mediastinal mesenchymal tumors affect distinct age groups or occur at specific mediastinal compartments. Neurogenic tumors, liposarcoma, solitary fibrous tumor, and synovial sarcoma are common mesenchymal tumors in the mediastinum. Herein, we provide an update on the diagnostic approach to mediastinal mesenchymal tumors and a review of the histologic features and differential diagnosis of common benign and malignant mesenchymal tumors of the mediastinum.
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http://dx.doi.org/10.1097/PAP.0000000000000306DOI Listing
September 2021

Mediastinal Germ Cell Tumors: A Review and Update on Pathologic, Clinical, and Molecular Features.

Adv Anat Pathol 2021 Sep;28(5):335-350

Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX.

Mediastinal germ cell tumors (MGCTs) are the most common extragonadal germ cell tumors (GCTs) and most often arise in the anterior mediastinum with a male predilection. MGCTs also have a predilection for patients with Klinefelter syndrome and possibly other genetic conditions. MGCTs, as GCTs at other extragonadal sites, are thought to arise from germ cells improperly retained during migration along the midline during embryogenesis. Similar to their counterparts in the testes, MGCTs are classified into seminomatous and nonseminomatous GCTs. Seminomatous MGCT represents pure seminoma, whereas nonseminomatous MGCTs encompass pure yolk sac tumors, embryonal carcinoma, choriocarcinoma, mature or immature teratoma, and mixed GCTs with any combination of GCT types, including seminoma. Somatic-type or hematologic malignancies can also occur in association with a primary MGCT. MGCTs share molecular findings with GCTs at other sites, most commonly the presence of chromosome 12p gains and isochromosome i(12p). Treatment includes neoadjuvant chemotherapy followed by surgical resection of residual tumor, with the exception of benign teratomas, which require only surgical resection without chemotherapy. In this review, we highlight and provide an update on pathologic, clinical, and molecular features of MGCTs. Immunohistochemical profiles of each tumor type, as well as differential diagnostic considerations, are discussed.
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http://dx.doi.org/10.1097/PAP.0000000000000304DOI Listing
September 2021

ISUP Consensus Definition of Cribriform Pattern Prostate Cancer.

Am J Surg Pathol 2021 08;45(8):1118-1126

Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.

The presence of a cribriform pattern is now recognized as a clinically important, independent adverse prognostic indicator for prostate cancer. For this reason the International Society of Urological Pathology (ISUP) recently recommended its inclusion in standard reporting. In order to improve interobserver agreement as to the diagnosis of cribriform patterns, the ISUP assembled an international panel of 12 expert urogenital pathologists for the purpose of drafting a consensus definition of cribriform pattern in prostate cancer, and provide their opinions on a set of 32 images and on potential diagnostic criteria. These images were selected by the 2 nonvoting convenors of the study and included the main categories where disagreement was anticipated. The Delphi method was applied to promote consensus among the 12 panelists in their review of the images during 2 initial rounds of the study. Following a virtual meeting, convened to discuss selected images and diagnostic criteria, the following definition for cribriform pattern in prostate cancer was approved: "A confluent sheet of contiguous malignant epithelial cells with multiple glandular lumina that are easily visible at low power (objective magnification ×10). There should be no intervening stroma or mucin separating individual or fused glandular structures" together with a set of explanatory notes. We believe this consensus definition to be practical and that it will facilitate reproducible recognition and reporting of this clinically important pattern commonly seen in prostate cancer. The images and the results of the final Delphi round are available at the ISUP website as an educational slide set (https://isupweb.org/isup/blog/slideshow/cribriform-slide-deck/).
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http://dx.doi.org/10.1097/PAS.0000000000001728DOI Listing
August 2021

Osseous Metaplasia in Hemangiomas of the Breast: Case Reports and Literature Review.

J Breast Cancer 2021 Apr 8;24(2):229-234. Epub 2021 Feb 8.

Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, USA.

Unusual or prominent calcifications found on screening mammography may prompt additional radiologic and clinical work-up given the possible association with pre-malignant lesions, other high-risk lesions, or malignancies. Osseous metaplasia (OM) of the breast, also referred to as metaplastic ossification or heterotopic bone formation, is an uncommon finding that may present as radiographic calcification. There are isolated case reports of OM associated with benign or malignant tumors of the breast, as well as with a variety of non-neoplastic conditions. We report 2 cases of OM in the breast associated with a hemangioma and review the relevant literature. To the best of our knowledge, these are the first reported cases of this association in the breast.
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http://dx.doi.org/10.4048/jbc.2021.24.e7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090807PMC
April 2021

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

Ann Diagn Pathol 2021 Jun 22;52:151733. Epub 2021 Mar 22.

Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.

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.
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http://dx.doi.org/10.1016/j.anndiagpath.2021.151733DOI Listing
June 2021

Pleomorphic giant cell carcinoma of prostate: Rare tumor with unique clinicopathological, immunohistochemical, and molecular features.

Ann Diagn Pathol 2021 Jun 17;52:151719. Epub 2021 Feb 17.

Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX 77030, USA; Weill Medical College of Cornell University (WCMC), New York, NY 10065, USA. Electronic address:

Pleomorphic giant cell carcinoma (PGCC) of the prostate is a rare entity categorized as a variant of prostatic acinar adenocarcinoma in the 2016 World Health Organization (WHO) classification system. PGCC differs from conventional prostatic adenocarcinoma by having bizarre, markedly enlarged, and pleomorphic cells. It differs from high grade urothelial carcinoma by negativity for urothelial differentiation markers, and can be distinguished from sarcomatoid carcinoma by lack of spindle cells. Including two new cases described herein, there have been 51 cases of prostate PGCC reported in the English literature. Clinical features shared by cases of prostate PGCC include poor prognosis, occurrence in older patients, and frequent association with prior therapy. Pathologic features common to cases of prostate PGCC include admixture with a high-grade conventional prostate carcinoma component and absent or reduced expression of prostate differentiation markers. More recent studies have begun to elucidate the molecular characteristics of PGCC, detecting specific mutations and chromosomal translocations, and showing evidence of a high degree of molecular instability in these tumors. We report novel findings in two cases of PGCC including a PIK3CA p.His1047Arg mutation not previously described. One of our cases is the first to clearly demonstrate chronological loss of prostate markers during dedifferentiation from prior conventional prostate carcinoma to PGCC. Herein, we present our two new cases and comprehensively review the literature on all reported cases of PGCC with critical commentary on findings in cases of this rare tumor.
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http://dx.doi.org/10.1016/j.anndiagpath.2021.151719DOI Listing
June 2021

Diagnostic approach in TFE3-rearranged renal cell carcinoma: a multi-institutional international survey.

J Clin Pathol 2021 May 29;74(5):291-299. Epub 2021 Jan 29.

Pathology, University Hospital Center of Martinique, Fort-de-France, Martinique.

Transcription factor E3-rearranged renal cell carcinoma (TFE3-RCC) has heterogenous morphologic and immunohistochemical (IHC) features.131 pathologists with genitourinary expertise were invited in an online survey containing 23 questions assessing their experience on TFE3-RCC diagnostic work-up.Fifty (38%) participants completed the survey. 46 of 50 participants reported multiple patterns, most commonly papillary pattern (almost always 9/46, 19.5%; frequently 29/46, 63%). Large epithelioid cells with abundant cytoplasm were the most encountered cytologic feature, with either clear (almost always 10/50, 20%; frequently 34/50, 68%) or eosinophilic (almost always 4/49, 8%; frequently 28/49, 57%) cytology. Strong (3+) or diffuse (>75% of tumour cells) nuclear TFE3 IHC expression was considered diagnostic by 13/46 (28%) and 12/47 (26%) participants, respectively. Main TFE3 IHC issues were the low specificity (16/42, 38%), unreliable staining performance (15/42, 36%) and background staining (12/42, 29%). Most preferred IHC assays other than TFE3, cathepsin K and pancytokeratin were melan A (44/50, 88%), HMB45 (43/50, 86%), carbonic anhydrase IX (41/50, 82%) and CK7 (32/50, 64%). Cut-off for positive fluorescent in situ hybridisation (FISH) was preferably 10% (9/50, 18%), although significant variation in cut-off values was present. 23/48 (48%) participants required FISH testing to confirm TFE3-RCC regardless of the histomorphologic and IHC assessment. 28/50 (56%) participants would request additional molecular studies other than FISH assay in selected cases, whereas 3/50 participants use additional molecular cases in all cases when TFE3-RCC is in the differential.Optimal diagnostic approach on TFE3-RCC is impacted by IHC and/or FISH assay preferences as well as their conflicting interpretation methods.
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http://dx.doi.org/10.1136/jclinpath-2020-207372DOI Listing
May 2021

The 2020 WHO Classification of Tumors of Bone: An Updated Review.

Adv Anat Pathol 2021 May;28(3):119-138

Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Weill Medical College of Cornell University, Houston, TX.

Bone tumors are a rare and heterogeneous group of neoplasms that occur in the bone. The diversity and considerable morphologic overlap of bone tumors with other mesenchymal and nonmesenchymal bone lesions can complicate diagnosis. Accurate histologic diagnosis is crucial for appropriate management and prognostication. Since the publication of the fourth edition of the World Health Organization (WHO) classification of tumors of soft tissue and bone in 2013, significant advances have been made in our understanding of bone tumor molecular biology, classification, prognostication, and treatment. Detection of tumor-specific molecular alterations can facilitate the accurate diagnosis of histologically challenging cases. The fifth edition of the 2020 WHO classification of tumors of soft tissue and bone tumors provides an updated classification scheme and essential diagnostic criteria for bone tumors. Herein, we summarize these updates, focusing on major changes in each category of bone tumor, the newly described tumor entities and subtypes of existing tumor types, and newly described molecular and genetic data.
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http://dx.doi.org/10.1097/PAP.0000000000000293DOI Listing
May 2021

Pathogenesis and Diagnosis of Genitourinary Cancer.

Cancers (Basel) 2021 Jan 19;13(2). Epub 2021 Jan 19.

Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Weill Medical College of Cornell University, 6565 Fannin St, Houston, TX 77030, USA.

Genitourinary (GU) cancers are among the most common malignant diseases in men [...].
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http://dx.doi.org/10.3390/cancers13020347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832837PMC
January 2021

Leiomyoadenomatoid Tumor of Epididymis: A Variant of Adenomatoid Tumor.

Ann Clin Lab Sci 2020 Nov;50(6):813-817

Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX

Adenomatoid tumor is a rare tumor of mesothelial origin, usually arising in the epididymis. It is the most common paratesticular tumor of middle-aged men. A rare variant of adenomatoid tumor is leiomyoadenomatoid tumor which is characterized by prominent spindle cell myoblastic and myofibroblastic proliferation in the background of an adenomatoid tumor with tubular spaces lined by mesothelial cells. In some cases, the spindle cell component obscures the adenomatoid tumor component, complicating accurate diagnosis. Here, we report two cases of paratesticular leiomyoadenomatoid tumor in 28-year-old and 50-year-old patients. The tumors from both cases were centered in the epididymis and measured 1.0 cm and 3.0 cm, respectively. Both had similar morphology with myofibroblastic proliferation in one case and myoblastic (smooth muscle) proliferation in the other. Both cases followed a benign course without local recurrence or distant metastasis for 14 and 22 months postoperatively, respectively. We propose the use of the term "adenomyomatoid tumor" to describe a neoplasm exhibiting adenomatoid tumor admixed with either leiomyomatous or myofibroblastic proliferation.
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November 2020

Leiomyoma of digit of hand: Report of three cases with literature review.

Ann Diagn Pathol 2021 Feb 14;50:151669. Epub 2020 Nov 14.

Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA; Weill Medical College of Cornell University, NY, New York, USA. Electronic address:

Leiomyoma is a benign tumor of smooth muscle origin most common in areas of the body with abundant smooth muscle including the gynecologic, genitourinary, and gastrointestinal system. Leiomyoma outside of these locations is believed to arise from vascular smooth muscle and arrector pili muscles. Leiomyoma of an extremity is a rare diagnosis, especially when present in a digit of the hand due to the paucity of smooth muscle in this location. We report three cases of leiomyoma of a digit of the hand.
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http://dx.doi.org/10.1016/j.anndiagpath.2020.151669DOI Listing
February 2021

The 2020 WHO Classification of Tumors of Soft Tissue: Selected Changes and New Entities.

Adv Anat Pathol 2021 Jan;28(1):44-58

Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Weill Medical College of Cornell University, Houston, TX.

Soft tissue tumors are a relatively rare and diagnostically challenging group of neoplasms that can have varying lines of differentiation. Accurate diagnosis is important for appropriate treatment and prognostication. In the 8 years since the publication of the 4th Edition of World Health Organization (WHO) classification of soft tissue tumors, significant advances have been made in our understanding of soft tissue tumor molecular biology and diagnostic criteria. The 5th Edition of the 2020 WHO classification of tumors of soft tissue and bone incorporated these changes. Classification of tumors, in general, but particularly in soft tissue tumors, is increasingly based on the molecular characteristics of tumor types. Understanding tumor molecular genetics improves diagnostic accuracy for tumors that have been difficult to classify on the basis of morphology alone, or that have overlapping morphologic features. In many large hospitals in the United States and Europe, molecular tests on soft tissue tumors are a routine part of diagnosis. Therefore, surgical pathologists should be familiar with newly emerging molecular genetic techniques in clinical settings. In the near future, molecular tests, particularly in soft tissue tumor diagnosis, will become as routine during diagnosis as immunohistochemistry is currently. This new edition provides an updated classification scheme and essential diagnostic criteria for soft tissue tumors. Newly recognized entities and subtypes of existing tumor types, several reclassified tumors, and newly defined molecular and genetic data have been incorporated. Herein, we summarize the updates in the WHO 5th Edition, focusing on major changes in each category of soft tissue tumor, and the newly described tumor entities and subtypes.
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http://dx.doi.org/10.1097/PAP.0000000000000284DOI Listing
January 2021

Seminal vesicle invasion combined with extraprostatic extension is associated with higher frequency of biochemical recurrence and lymph node metastasis than seminal vesicle invasion alone: Proposal for further pT3 prostate cancer subclassification.

Ann Diagn Pathol 2020 Dec 24;49:151611. Epub 2020 Aug 24.

Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Weill Medical College of Cornell University, Houston, Texas, USA. Electronic address:

The 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system subdivides prostatic pT3 tumors into pT3a, which includes cases with extraprostatic extension (EPE) and pT3b, which is defined by the presence of seminal vesicle invasion (SVI) with or without EPE. Yet, it is not established whether combined SVI and EPE impart a worse prognosis compared to SVI alone. We studied a cohort of 69 prostatectomy patients with SVI with or without EPE. Patient age at the time of radical prostatectomy was documented and Gleason score and presence or absence of EPE and/or SVI were determined. Biochemical recurrence (BCR) was defined as a PSA rise >0.2 ng/mL. The frequency of BCR was 33.9% in cases with combined EPE and SVI versus 12.5% in cases with SVI alone (relative risk = 2.71). An additional cohort of 88 patients also showed a higher frequency of lymph node metastasis of 29% in patients with combined SVI and EPE at the time of radical prostatectomy versus a 10% frequency of lymph node metastasis in patients with SVI alone (relative risk = 2.9). Based on our data, we propose further subdividing pT3 prostate cancers into three groups: EPE alone (pT3a), SVI alone (pT3b), and combined EPE and SVI (pT3c). This classification system would more accurately identify patients with pT3 prostate cancer who are more likely to experience worse outcomes and provide clinicians with additional information to aid in follow-up and postoperative treatment decisions.
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http://dx.doi.org/10.1016/j.anndiagpath.2020.151611DOI Listing
December 2020

Retroperitoneal Sarcomas: An Update on the Diagnostic Pathology Approach.

Diagnostics (Basel) 2020 Aug 27;10(9). Epub 2020 Aug 27.

Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Weill Medical College of Cornell University, Houston, TX 77030, USA.

Retroperitoneal sarcomas are a heterogenous group of rare tumors arising in the retroperitoneum. Retroperitoneal sarcomas comprise approximately 10% of all soft tissue sarcomas. Though any soft tissue sarcoma histologic types may arise in the retroperitoneal space, liposarcoma (especially well-differentiated and dedifferentiated types) and leiomyosarcoma do so most commonly. Retroperitoneal sarcomas are diagnostically challenging, owing to their diversity and morphological overlap with other tumors arising in the retroperitoneum. An accurate diagnosis is necessary for correct management and prognostication. Herein, we provide an update on the diagnostic approach to retroperitoneal sarcomas and review their key histologic findings and differential diagnoses.
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http://dx.doi.org/10.3390/diagnostics10090642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555595PMC
August 2020

Anastomosing Hemangioma of the Breast: An Unusual Case at an Unusual Site.

J Breast Cancer 2020 Jun 17;23(3):326-330. Epub 2020 Feb 17.

Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Weill Medical College of Cornell University, Houston, Texas, USA.

Anastomosing hemangioma (AH) is an unusual benign vascular lesion that commonly occurs in the kidney and genitourinary tract. We report a case of AH in a 49-year-old woman presenting as a mass in the breast, a site which, to the best of our knowledge, has not been previously documented in the English literature. Microscopic examination of the mass revealed a well-demarcated proliferation of anastomosing vascular spaces lined by bland endothelial cells, with focal hobnailing and scattered intravascular fibrin thrombi. No mitotic activity was observed and the Ki-67 proliferative index was low. These features were interpreted as AH, a lesion that may be difficult to distinguish from low-grade angiosarcoma or other benign vascular lesions of the breast which may demonstrate anastomosing channels. Due to the presence of atypical histologic features which can raise suspicion for angiosarcoma on biopsy, complete excision of these lesions is recommended for optimal treatment.
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http://dx.doi.org/10.4048/jbc.2020.23.e15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311365PMC
June 2020

Lesions of anogenital mammary-like glands: Four cases including novel pathologic and immunohistochemical observations.

Ann Diagn Pathol 2020 Aug 17;47:151551. Epub 2020 Jun 17.

Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Weill Medical College of Cornell University, Houston, TX, USA. Electronic address:

Anogenital mammary-like glands, formerly described as ectopic breast tissue, are currently considered to be normal histologic components of the anogenital region. Anogenital mammary-like glands can give rise to many lesions identical to counterparts in the native female breast. We describe four cases of such lesions, including fibroadenoma, gynecomastia-like hyperplasia, and ectopic mammary-type tissue with a spectrum of usual ductal hyperplasia, apocrine metaplasia, adenosis, and pseudolactational change. All four cases occurred in young women (ages 29-38) who presented with vulvar or perianal masses. Similar to previously reported cases, these lesions shared histologic and immunohistochemical characteristics identical to native female breast lesions. Novel findings in our cases included (1) the first case of gynecomastia-like change to be reported in the perianal area of a female, (2) Immunohistochemical staining identifying a 3-layered epithelium characterized by a population of CK14 and CK5/6 positive and hormone receptor negative superficial luminal cells, and (3) diffuse, strong positivity for GATA3 in all cases. Our study adds to the literature on these rare lesions and highlights findings which may be useful in understanding the pathogenesis and improving the diagnosis of anogenital mammary-like gland lesions.
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http://dx.doi.org/10.1016/j.anndiagpath.2020.151551DOI Listing
August 2020

Epithelioid Cutaneous Mesenchymal Neoplasms: A Practical Diagnostic Approach.

Diagnostics (Basel) 2020 Apr 17;10(4). Epub 2020 Apr 17.

Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Weill Medical College of Cornell University, Houston, TX 77030, USA.

Epithelioid cells are rounded or polygonal cells with abundant eosinophilic or clear cytoplasm and ovoid to round nuclei, superficially resembling epithelial cells. Cutaneous mesenchymal neoplasms composed predominantly or exclusively of epithelioid cells are relatively uncommon and can cause considerable diagnostic difficulties due to overlapping histologic features among heterogeneous groups of tumors. Familiarity with practical diagnostic approaches and recognition of key histopathologic features are important for correct diagnosis and management. This review summarizes the histologic features of epithelioid cutaneous mesenchymal neoplasms and discusses their differential diagnoses from malignant melanomas and carcinomas.
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http://dx.doi.org/10.3390/diagnostics10040233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236000PMC
April 2020

Double cocktail immunostains with high molecular weight cytokeratin and GATA-3: useful stain to discriminate in situ involvement of prostatic ducts or acini from stromal invasion by urothelial carcinoma in the prostate.

J Pathol Transl Med 2020 Mar 10;54(2):146-153. Epub 2020 Feb 10.

Department of Pathology and Genomic Medicine, Houston Methodist Hospital and Weill Medical College of Cornell University, Houston, TX, USA.

Background: Distinguishing prostatic stromal invasion (PSI) by urothelial carcinoma (UC) from in situ UC involving prostatic ducts or acini with no stromal invasion (in situ involvement) may be challenging on hematoxylin and eosin stained sections. However, the distinction between them is important because cases with PSI show worse prognosis. This study was performed to assess the utility of double cocktail immunostains with high molecular weight cytokeratin (HMWCK) and GATA-3 to discriminate PSI by UC from in situ UC involvement of prostatic ducts or acini in the prostate.

Methods: Among 117 radical cystoprostatectomy specimens for bladder UCs, 25 cases showed secondary involvement of bladder UC in prostatic ducts/acini only or associated stromal invasion and of these 25 cases, seven cases revealed equivocal PSI. In these seven cases with equivocal PSI, HMWCK, and GATA-3 double immunohistochemical stains were performed to identify whether this cocktail stain is useful to identify the stromal invasion.

Results: In all cases, basal cells of prostate glands showed strong cytoplasmic staining for HMWCK and UC cells showed strong nuclear staining for GATA-3. In cases with stromal invasion of UC, GATA-3-positive tumor cells in the prostatic stroma without surrounding HMWCK-positive basal cells were highlighted and easily recognized. Among seven equivocal cases, two cases showed PSI and five in situ UC in the prostate. In two cases, the original diagnoses were revised.

Conclusions: Our study suggested that HMWCK and GATA-3 double stains could be utilized as an adjunct method in the distinction between PSI by UC from in situ UC involving prostatic ducts or acini.
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http://dx.doi.org/10.4132/jptm.2019.11.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093285PMC
March 2020

Plasmacytoid Variant Urothelial Carcinoma of the Bladder: A Systematic Review and Meta-Analysis of Clinicopathological Features and Survival Outcomes.

J Urol 2020 08 31;204(2):215-223. Epub 2020 Jan 31.

Department of Urology, Gangnam Severance Hospital, Urological Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.

Purpose: The clinicopathological features and treatment outcomes of plasmacytoid variant-urothelial carcinoma of the bladder have not been fully understood. We evaluated the clinicopathological characteristics and survival outcomes of plasmacytoid variant-urothelial carcinoma of the bladder compared to conventional urothelial carcinoma of the bladder.

Materials And Methods: A systematic review was performed following the PRISMA guideline. PubMed®/MEDLINE®, Embase® and Cochrane Library were searched up to June 2019. The differences in the clinicopathological features (stage pT3 or greater, lymph node metastasis, ureteral margin positive and perivesical soft tissue margin positive status) and survival outcomes (overall mortality and cancer specific mortality) between plasmacytoid variant-urothelial carcinoma of the bladder and conventional urothelial carcinoma of the bladder were compared. The GRADE approach was used for rating the certainty of evidence.

Results: Eight studies were included. Patients with plasmacytoid variant-urothelial carcinoma of the bladder had a higher frequency of stage pT3 or greater (OR 3.84, 95% CI 1.63-9.03, p=0.002) and risk of lymph node metastasis (OR 2.58, 95% CI 1.15-5.76, p=0.02), ureteral margin positive (OR 12.18, 95% CI 4.62-32.13, p <0.00001) and perivesical soft tissue margin positive (OR 12.31, 95% CI 5.15-29.41, p <0.00001) status after radical cystectomy than those with conventional urothelial carcinoma of the bladder. Although there was no difference in cancer specific mortality (HR 1.40, 95% CI 0.82-2.40, p=0.22) between plasmacytoid variant-urothelial carcinoma of the bladder and conventional urothelial carcinoma of the bladder, plasmacytoid variant-urothelial carcinoma of the bladder had worse survival outcomes (overall mortality) than conventional urothelial carcinoma of the bladder approaching the borderline of significance (HR 1.62, 95% CI 0.98-2.68, p=0.06) when adjusted for other clinicopathological characteristics.

Conclusions: Plasmacytoid variant-urothelial carcinoma of the bladder was strongly associated with adverse clinicopathological features and worse overall mortality compared to conventional urothelial carcinoma of the bladder after adjusting for other clinicopathological parameters, and plasmacytoid variant histology of urothelial carcinoma of the bladder is an independent prognostic factor for overall survival.
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http://dx.doi.org/10.1097/JU.0000000000000794DOI Listing
August 2020

Reporting Practices and Resource Utilization in the Era of Intraductal Carcinoma of the Prostate: A Survey of Genitourinary Subspecialists.

Am J Surg Pathol 2020 05;44(5):673-680

Cleveland Clinic, Cleveland, OH.

Intraductal carcinoma of the prostate (IDC-P) has been recently recognized by the World Health Organization classification of prostatic tumors as a distinct entity, most often occurring concurrently with invasive prostatic adenocarcinoma (PCa). Whether documented admixed with PCa or in its rare pure form, numerous studies associate this entity with clinical aggressiveness. Despite increasing clinical experience and requirement of IDC-P documentation in protocols for synoptic reporting, the specifics of its potential contribution to assessment of grade group (GG) and cancer quantitation of PCa in both needle biopsies (NBx) and radical prostatectomy (RP) specimens remain unclear. Moreover, there are no standard guidelines for incorporating basal cell marker immunohistochemistry (IHC) in the diagnosis of IDC-P, either alone or as part of a cocktail with AMACR/racemase. An online survey containing 26 questions regarding diagnosis, reporting practices, and IHC resource utilization, focusing on IDC-P, was undertaken by 42 genitourinary subspecialists from 9 countries. The degree of agreement or disagreement regarding approaches to individual questions was classified as significant majority (>75%), majority (51% to 75%), minority (26% to 50%) and significant minority (≤25%). IDC-P with or without invasive cancer is considered a contraindication for active surveillance by the significant majority (95%) of respondents, although a majority (66%) also agreed that the clinical significance/behavior of IDC-P on NBx or RP with PCa required further study. The majority do not upgrade PCa based on comedonecrosis seen only in the intraductal component in NBx (62%) or RP (69%) specimens. Similarly, recognizable IDC-P with GG1 PCa was not a factor in upgrading in NBx (78%) or RP (71%) specimens. The majority (60%) of respondents include readily recognizable IDC-P in assessment of linear extent of PCa at NBx. A significant majority (78%) would use IHC to confirm or exclude intraductal carcinoma if other biopsies showed no PCa, while 60% would use it to confirm IDC-P with invasive PCa in NBx if it would change the overall GG assignment. Nearly half (48%, a minority) would use IHC to confirm IDC-P for accurate Gleason pattern 4 quantitation. A majority (57%) report the percentage of IDC-P when present, in RP specimens. When obvious Gleason pattern 4 or 5 PCa is present in RP or NBx, IHC is rarely to almost never used to confirm the presence of IDC-P by the significant majority (88% and 90%, respectively). Most genitourinary pathologists consider IDC-P to be an adverse prognostic feature independent of the PCa grade, although recommendations for standardization are needed to guide reporting of IDC-P vis a vis tumor quantitation and final GG assessment. The use of IHC varies widely and is performed for a multitude of indications, although it is used most frequently in scenarios where confirmation of IDC-P would impact the GG assigned. Further study and best practices recommendations are needed to provide guidance with regards to the most appropriate indications for IHC use in scenarios regarding IDC-P.
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http://dx.doi.org/10.1097/PAS.0000000000001417DOI Listing
May 2020

Clinicopathologic study of 60 cases of urothelial neoplasms with inverted growth patterns: Reclassification by international consultation on urologic disease (ICUD) recommendations.

Ann Diagn Pathol 2020 Feb 22;44:151433. Epub 2019 Nov 22.

Department of Pathology and Genomic Medicine, The Methodist Hospital and Weill Medical College of Cornell University, Houston, TX 77030, USA. Electronic address:

Background: Most urothelial neoplasms of the bladder show an exophytic papillary pattern, but some show an inverted growth pattern. In 2004, the World Health Organization (WHO) released a detailed histologic classification system for papillary urothelial neoplasms, but not for inverted forms. The International Consultation on Urologic Disease (ICUD) recommendations of 2012 are applicable to inverted/endophytic papillary lesions as follows: 1) inverted papilloma (IP), 2) inverted papillary urothelial neoplasm of low malignant potential (IPUNLMP), 3) inverted papillary urothelial carcinoma, low grade, non-invasive (IPUCLG-NI), 4) inverted papillary urothelial carcinoma, high grade, non-invasive (IPUCHG-NI), 5) inverted papillary urothelial carcinoma, high grade, invasive (IPUCHG-I). However, only atypical cellular morphology was considered for classification in the 2012 ICUD recommendations, and data to support to validate this new grading system are lacking.

Methods: Sixty cases of inverted urothelial papillary tumors were classified into 5 categories according to 2012 ICUD and 2016 WHO/ISUP recommendations to evaluate their clinical, pathological, and immunohistochemical characteristics. Two subgroups were defined as subgroup 1, IP and IPUNLMP, and subgroup 2, IPUCLG-NI, IPUCHG-NI, and IPUCHG-I. Clinical features (age, sex, history of urothelial carcinoma, smoking history, size, and multifocality) and histologic features (nuclear pleomorphism, mitotic count, mitosis level, apoptosis, luminal necrosis, trabecular thickening, anastomosing trabeculae, hypercellularity, loss of polarity, peripheral palisading, palisading with central streaming, and discohesiveness) were evaluated. Immunohistochemical stains for CK20, CD44, P53, p16, Ki-67, cyclin D1 and c-erbB2 were performed.

Results: A total of 60 cases were classified as 10 cases of IP, 29 cases of IPUNLMPs, 15 cases of IPUCLG-NI, 4 cases of IPUCHG-NI, and 2 cases of IPUCHG-I. Compared to subgroup 1, subgroup 2 showed larger tumor size, more nuclear irregularity, higher mitotic count (hot spot and per 10 high power fields), more upper level mitosis (>1/2), and more frequent apoptosis, luminal necrosis, surface papillary component, trabecular thickening, anastomosing irregular trabeculae, hypercellularity, loss of polarity, peripheral palisading with central streaming, and discohesiveness, and absence of umbrella cells and urothelial eddies. CK20, Ki67, and c-erbB2 were the only markers that were differently expressed in the two subgroups, with more expression in subgroup 2.

Conclusions: The 2012 ICUD recommendations are valid to classify inverted papillary urothelial tumors. However, other histologic features besides atypical cellular morphology should also be considered to distinguish subgroup 1 and subgroup 2 inverted papillary urothelial tumors.
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http://dx.doi.org/10.1016/j.anndiagpath.2019.151433DOI Listing
February 2020

Neuroendocrine tumors of genitourinary tract: Recent advances.

Ann Diagn Pathol 2019 Oct 21;42:48-58. Epub 2019 Jun 21.

Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA; Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY, USA. Electronic address:

Primary neuroendocrine tumors of the genitourinary tract are rare and are comprised of a heterogeneous group of neoplasms. These include paraganglioma, well-differentiated neuroendocrine tumors or carcinoid tumors, small-cell neuroendocrine carcinoma, and large-cell neuroendocrine carcinoma. Personal experiences, in addition to the findings of an extensive literature search for pertinent publications, were used to compile the epidemiological data, clinical information, histopathological features, prognostic factors, and therapeutic approaches. We also include molecular alterations and targeted treatments of the various neuroendocrine tumors of the genitourinary tract.
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http://dx.doi.org/10.1016/j.anndiagpath.2019.06.009DOI Listing
October 2019

Solitary Fibrous Tumor of Breast with Anaplastic Areas (Malignant Solitary Fibrous Tumor): A Case Report with Review of Literature.

J Breast Cancer 2019 Jun 13;22(2):326-335. Epub 2019 Jun 13.

Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA.

Solitary fibrous tumor (SFT) is a rare, soft tissue neoplasm that rarely presents in breast tissue, with only 27 previously reported cases. To our knowledge, only one case of malignant SFT has been reported in the English literature. A 75-year-old Caucasian woman presented to our institution with a 3-month history of a palpable left breast mass. No other symptoms, including nipple discharge or skin changes, were noted. She underwent 3 previous biopsies for right breast masses, all of which were benign, with no evidence of spindle cell neoplasm, atypical hyperplasia, or malignancy. Microscopic examination of the mass demonstrated a classic area of SFT with areas of high-grade anaplastic component. In these areas, the tumor showed atypical epithelioid cells arranged in hypercellular sheets with diminished branching vasculature, nuclear pleomorphism, and increased mitotic count (up to 9/10 high-power fields). This case represents the second case of malignant SFT in the breast.
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http://dx.doi.org/10.4048/jbc.2019.22.e30DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597415PMC
June 2019

"Doctor, I Just Can't Seem to Swallow!"

Gastroenterology 2019 10 31;157(4):938-939. Epub 2019 May 31.

Houston Methodist hospital, Houston, Texas.

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http://dx.doi.org/10.1053/j.gastro.2019.05.061DOI Listing
October 2019

Micropapillary adenocarcinoma of lung: Morphological criteria and diagnostic reproducibility among pulmonary pathologists.

Ann Diagn Pathol 2019 Aug 24;41:43-50. Epub 2019 Apr 24.

Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Weill Medical College of Cornell University, Houston, TX, USA. Electronic address:

Context: Invasive micropapillary adenocarcinoma (MPC) is an aggressive variant of lung adenocarcinoma, frequently manifesting with advanced stage lymph node metastasis and decreased survival.

Objective: Identification of this morphology is important, as it is strongly correlated with poor prognosis regardless of the amount of MPC component. To date, no study has investigated the morphological criteria used to objectively diagnose it.

Design: Herein, we selected 30 cases of potential MPC of lung, and distributed 2 digital images per case among 15 pulmonary pathology experts. Reviewers were requested to diagnostically interpret, assign the percentage of MPC component, and record the morphological features they identified. The noted features included: columnar cells, elongated slender cell nests, extensive stromal retraction, lumen formation with internal epithelial tufting, epithelial signet ring-like forms, intracytoplasmic vacuolization, multiple nests in the same alveolar space, back-to-back lacunar spaces, epithelial nest anastomosis, marked pleomorphism, peripherally oriented nuclei, randomly distributed nuclei, small/medium/large tumor nest size, fibrovascular cores, and spread through air-spaces (STAS).

Results: Cluster analysis revealed three subgroups with the following diagnoses: "MPC", "combined papillary and MPC", and "others". The subgroups correlated with the reported median percentage of MPC. Intracytoplasmic vacuolization, epithelial nest anastomosis/confluence, multiple nests in the same alveolar space, and small/medium tumor nest size were the most common criteria identified in the cases diagnosed as MPC. Peripherally oriented nuclei and epithelial signet ring-like forms were frequently identified in both the "MPC" and "combined papillary and MPC" groups.

Conclusions: Our study provides objective diagnostic criteria to diagnose MPC of lung.
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http://dx.doi.org/10.1016/j.anndiagpath.2019.04.008DOI Listing
August 2019

The 58th Annual Symposium of the Houston Society of Clinical Pathologists.

Arch Pathol Lab Med 2019 05;143(5):548-549

From the Department of Pathology, University of Texas MD Anderson Cancer Center, Houston (Dr Guo); and the Department of Pathology and Genomic Medicine, Houston Methodist Hospital and Weill Medical College of Cornell University, Houston, Texas (Dr Ro).

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http://dx.doi.org/10.5858/arpa.2018-0236-EDDOI Listing
May 2019

Histologic Diagnosis of Renal Mass Biopsy.

Arch Pathol Lab Med 2019 06 10;143(6):705-710. Epub 2019 Apr 10.

From the Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas.

Context.—: Core biopsy has been increasingly used for clinical decision-making in the management of patients with renal masses. The sensitivity and specificity of histologic diagnoses of renal mass biopsies depend on many factors such as adequate sampling and tissue processing, diagnostic skill and experience, and appropriate use of ancillary techniques.

Objective.—: To review the indications, emphasize the importance of obtaining adequate diagnostic material, and introduce a general diagnostic approach, in conjunction with immunohistochemistry, in diagnosis of renal mass biopsies.

Data Sources.—: Literature review and personal experiences in daily practice and consultation diagnosis of renal masses in a large tertiary medical center.

Conclusions.—: For renal mass biopsies, it is critical to obtain adequate diagnostic material and establish a standard laboratory procedure in working with small biopsy specimens. The key for the diagnosis is to be familiar with different tumor entities with characteristic morphology and to understand the wide spectrum of tumor heterogeneity. By developing a systematic approach, one can categorize the tumor and create a sensible differential diagnosis based on the growth pattern and cellular morphology. Immunohistochemistry is particularly helpful for renal mass biopsy diagnosis in selected situations.
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http://dx.doi.org/10.5858/arpa.2018-0272-RADOI Listing
June 2019
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