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Volume 53(5); September 2019
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Original Articles
Human Papillomavirus Serologic Profiles of Selected Filipinos with Head and Neck Squamous Cell Carcinoma
Pia Marie Albano, Christianne Salvador, Jose Orosa, Sheryl Racelis, Modesty Leaño, Angelika Michel, John Donnie Ramos, Dana Holzinger, Michael Pawlita
J Pathol Transl Med. 2019;53(5):273-279.   Published online May 30, 2019
DOI: https://doi.org/10.4132/jptm.2019.05.12
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AbstractAbstract PDF
Background
The low prevalence of human papillomavirus (HPV) DNA and mRNA in biopsy samples of Filipinos with head and neck squamous cell carcinoma (HNSCC) has been reported previously. Here, the HPV serologic profiles of HNSCC cases were analyzed and associated with life-style and sexual practices.
Methods
Serum samples were collected between May 2012 and September 2013 from HNSCC patients (n = 22) in the northwest region of the Philippines, and age- and sex-matched clinically healthy controls. Antibodies to capsid and early oncoproteins of HPV16, 18, 31, 33, 45, 52, 58, 6, and 11 were analyzed using multiplex serology.
Results
Most of the cases were males with tumors of the oral cavity or larynx. Two of the cases tested positive for at least one of the early oncoproteins (E6, E7, E1, and/or E2) of HPV16, and 11 did not display reactivity to any HPV early or late oncoproteins. Of the controls, four tested positive for at least one of the HPV16 early oncoproteins, and 10 were non-reactive to all HPV types. Titers to HPV16 E6 or E7 of the seropositive cases and controls were considerably lower than those typically observed in economically developed countries.
Conclusions
The low HPV titers seen here are consistent with the results of molecular analyses for this population. Hence, the seropositivity of some of the HNSCC cases is likely an indication of prior exposure to the virus and not the presence of HPV-driven tumors.
High Expression of Galectin-1, VEGF and Increased Microvessel Density Are Associated with MELF Pattern in Stage I-III Endometrioid Endometrial Adenocarcinoma
Dmitry Aleksandrovich Zinovkin, Sergey Leonidovich Achinovich, Mikhail Grigoryevich Zubritskiy, Jacqueline Linda Whatmore, Md Zahidul Islam Pranjol
J Pathol Transl Med. 2019;53(5):280-288.   Published online June 27, 2019
DOI: https://doi.org/10.4132/jptm.2019.05.13
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  • 2 Citations
AbstractAbstract PDF
Background
In this study, we investigate the expression of markers of angiogenesis and microvessel density (MVD) in cases of microcystic, elongated and fragmented (MELF) pattern, with its prognostic role in the survival of endometrioid endometrial adenocarcinomas (EA) patients.
Methods
In this study, 100 cases of EA, 49 cases with MELF pattern and 51 without, were immunohistochemically stained for galectin-1, vascular endothelial growth factor (VEGF), and MVD. Morphometry and statistical (univariate and multivariate) analyses were performed to assess overall survival (OS) and disease-free survival.
Results
The expression of VEGF (p<.001) and galectin-1 (p<.001), as well as MVD area (p<.001) and number of vessels/mm2 (p<.050), were significantly higher in the +MELF pattern group compared to the –MELF group. A low negative correlation between MELFpattern and the number of days of survival (p<.001, r=–0.47) was also found. A low positive correlation of MELF-pattern with galectin-1 expression (p<.001, r=0.39), area of vessels/mm2 (p<.001, r=0.36), outcome of EA (p<.001, r=0.42) and VEGF expression (p<.001, r=0.39) suggests potential pathological relevance of these factors in the prognosis of EA. A univariate survival analysis indicated a role for all parameters of survival. Multivariate Cox proportional hazard regression analysis revealed that only area of vessels/mm2 (hazard ratio [HR], 1.018; 95% confidence interval [CI], 1.002 to 1.033), galectin-1 (HR, 1.049; 95% CI, 1.025 to 1.074) and VEGF (HR, 1.049; 95% CI, 1.022 to 1.077) play key roles in OS.
Conclusions
This study reports an increase in MVD, VEGF and galectin-1 expression in EA with MELF pattern and suggests that MELF pattern, along with the angiogenic profile, may be a prognostic factor in EA.
Clinicopathological Characterization and Prognostic Implication of SMAD4 Expression in Colorectal Carcinoma
Seung-Yeon Yoo, Ji-Ae Lee, Yunjoo Shin, Nam-Yun Cho, Jeong Mo Bae, Gyeong Hoon Kang
J Pathol Transl Med. 2019;53(5):289-297.   Published online June 24, 2019
DOI: https://doi.org/10.4132/jptm.2019.06.07
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  • 5 Citations
AbstractAbstract PDFSupplementary Material
Background
SMAD family member 4 (SMAD4) has gained attention as a promising prognostic factor of colorectal cancer (CRC) as well as a key molecule to understand the tumorigenesis and progression of CRC.
Methods
We retrospectively analyzed 1,281 CRC cases immunohistochemically for their expression status of SMAD4, and correlated this status with clinicopathologic and molecular features of CRCs.
Results
A loss of nuclear SMAD4 was significantly associated with frequent lymphovascular and perineural invasion, tumor budding, fewer tumor-infiltrating lymphocytes, higher pT and pN category, and frequent distant metastasis. In contrast, tumors overexpressing SMAD4 showed a significant association with sporadic microsatellite instability. After adjustment for TNM stage, tumor differentiation, adjuvant chemotherapy, and lymphovascular invasion, the loss of SMAD4 was found to be an independent prognostic factor for worse 5-year progression-free survival (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.01 to 1.60; p=.042) and 7-year cancerspecific survival (HR, 1.45; 95% CI, 1.06 to 1.99; p=.022).
Conclusions
We confirmed the value of determining the loss of SMAD4 immunohistochemically as an independent prognostic factor for CRC in general. In addition, we identified some histologic and molecular features that might be clues to elucidate the role of SMAD4 in colorectal tumorigenesis and progression.
Reclassification of Mongolian Diffuse Gliomas According to the Revised 2016 World Health Organization Central Nervous System Tumor Classification
Enkhee Ochirjav, Bayarmaa Enkhbat, Tuul Baldandorj, Gheeyoung Choe
J Pathol Transl Med. 2019;53(5):298-307.   Published online August 2, 2019
DOI: https://doi.org/10.4132/jptm.2019.07.15
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  • 1 Citations
AbstractAbstract PDF
Background
The 2016 World Health Organization (WHO) classification of central nervous system (CNS) tumors has been modified to incorporate the IDH mutation and 1p/19q co-deletion in the diagnosis of diffuse gliomas. In this study, we aimed to evaluate the feasibility and prognostic significance of the revised 2016 WHO classification of CNS tumors in Mongolian patients with diffuse gliomas.
Methods
A total of 124 cases of diffuse gliomas were collected, and tissue microarray blocks were made. IDH1 mutation was tested using immunohistochemistry, and 1p/19q co-deletion status was examined using fluorescence in situ hybridization analysis.
Results
According to the 2016 WHO classification, 124 cases of diffuse brain glioma were reclassified as follows: 10 oligodendroglioma, IDHmut and 1p/19q co-deleted; three anaplastic oligodendroglioma, IDHmut and 1p/19q co-deleted; 35 diffuse astrocytoma, IDHmut, 11 diffuse astrocytoma, IDHwt, not otherwise specified (NOS); 22 anaplastic astrocytoma, IDHmut, eight anaplastic astrocytoma, IDHwt, NOS; and 35 glioblastoma, IDHwt, NOS, respectively. The 2016 WHO classification presented better prognostic value for overall survival in patients with grade II tumors than traditional histological classification. Among patients with grade II tumors, those with oligodendroglioma IDHmut and 1p/19q co-deleted and diffuse astrocytoma IDHmut showed significantly higher survival than those with diffuse astrocytoma IDHwt, NOS (p<.01).
Conclusions
Mongolian diffuse gliomas could be reclassified according to the new 2016 WHO classification. Reclassification revealed substantial changes in diagnosis of both oligodendroglial and astrocytic entities. We have confirmed that the revised 2016 WHO CNS tumor classification has prognostic significance in Mongolian patients with diffuse gliomas, especially those with grade II tumors.
Primary Rhabdomyosarcoma of the Breast: Study of Three Cases at One Institution with a Review of Primary Breast Sarcomas
Junyoung Shin, Hee Jeong Kim, Dae-Yeon Kim, Gyungyub Gong, Kyung-Ja Cho
J Pathol Transl Med. 2019;53(5):308-316.   Published online August 2, 2019
DOI: https://doi.org/10.4132/jptm.2019.07.22
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  • 4 Citations
AbstractAbstract PDF
Background
Primary breast sarcoma (PBS) is rare, comprising approximately 1% of breast malignancies. Rhabdomyosarcoma (RMS) accounts for an extremely small proportion of PBSs, often leading to delayed histologic confirmation.
Methods
Upon reviewing Asan Medical Center’s pathology database between 2000 and 2018, 41 PBS cases were retrieved, including three cases of primary RMS of the breast. Their clinicopathological features were analyzed, and the literature related to PBS and primary RMS of the breast was reviewed.
Results
We identified three primary breast RMS cases from our institution database, comprising 7.3% of PBS: one case each of spindle cell/sclerosing RMS (ssRMS), alveolar RMS (aRMS), and embryonal RMS (eRMS). All cases involved adolescents or young adults (14, 16, and 25 years, respectively) who underwent mastectomy or radiotherapy and were confirmed using immunohistochemical testing for myogenin, desmin, and myogenic differentiation. The ssRMS patient experienced recurrence at the operation site 4 months post-surgery despite undergoing concurrent chemoradiotherapy. The aRMS patient had multiple metastases at diagnosis and showed FAX3-FOXO1 fusion transcripts; she died 22 months after the diagnosis. The eRMS patient had enlarged axillary lymph nodes; post-radiotherapy, the lesion recurred as multiple metastases to the bone and lung. She died 18 months post-diagnosis.
Conclusions
Our experience on RMS cases suggests that spindle cell or small round cell malignancy in breasts of young female should raise suspicion for the possibility of primary or secondary RMS. To our knowledge, this is the second report of primary breast ssRMS and it may help clinicians who encounter this rare disease in the future.
Multistaining Optimization for Epstein-Barr Virus–Encoded RNA In Situ Hybridization and Immunohistochemistry of Formalin-Fixed Paraffin-Embedded Tissues Using an Automated Immunostainer
Jae Nam Ko, Jin Kyoung Jung, Yun Ik Park, Hwa Jeong Shin, Jooryung Huh, Sol Back, Yu Jin Kim, Jae Ho Kim, Heounjeong Go
J Pathol Transl Med. 2019;53(5):317-326.   Published online August 27, 2019
DOI: https://doi.org/10.4132/jptm.2019.08.06
  • 4,862 View
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  • 1 Citations
AbstractAbstract PDFSupplementary Material
Background
Single staining is commonly performed for practical pathologic diagnoses. However, this method is limited in its ability to specify cellular morphology and immunophenotype and often requires consumption of limited tissue. This study aimed to describe an optimized protocol for multiple in situ hybridization (ISH) and immunohistochemistry (IHC).
Methods
The quality of multistaining was evaluated by carefully changing each step of ISH and IHC in an angioimmunoblastic T-cell lymphoma (AITL) case on a Ventana BenchMark XT automated immunostainer. The optimized protocols were also performed using another immunostainer and in 15 cases of five Epstein-Barr virus (EBV)–associated malignancies using formalin-fixed paraffin-embedded tissue.
Results
The quality of various ISHIHC staining protocols was semi-quantitatively evaluated. The best EBV-encoded RNA (EBER)-ISH/double IHC staining quality, equivalent to single staining, was obtained using the following considerations: initial EBER-ISH application, use of protease and antigen retrieval reagent (cell conditioning 1 [CC1] treatment time was minimized due to impact on tissue quality), additional baking/ deparaffinization not needed, and reduced dilution ratio and increased reaction time for primary antibody compared with single immunostaining. Furthermore, shorter second CC1 treatment time yielded better results. Multiple staining was the best quality in another immunostainer and for different types of EBV-associated malignancies when it was performed in the same manner as for the Ventana BenchMark XT as determined for AITL.
Conclusions
EBER-ISH and double IHC could be easily used in clinical practice with currently available automated immunostainers and adjustment of reagent treatment time, dilution ratio, and antibody reaction time.
Case Studies
Amoebic Encephalitis Caused by Balamuthia mandrillaris
Su Jung Kum, Hye Won Lee, Hye Ra Jung, Misun Choe, Sang Pyo Kim
J Pathol Transl Med. 2019;53(5):327-331.   Published online May 24, 2019
DOI: https://doi.org/10.4132/jptm.2019.05.14
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  • 8 Citations
AbstractAbstract PDF
We present the case of a 71-year-old man who was diagnosed with amoebic encephalitis caused by Balamuthia mandrillaris. He had rheumatic arthritis for 30 years and had undergone continuous treatment with immunosuppressants. First, he complained of partial spasm from the left thigh to the left upper limb. Magnetic resonance imaging revealed multifocal enhancing nodules in the cortical and subcortical area of both cerebral hemispheres, which were suggestive of brain metastases. However, the patient developed fever with stuporous mentality and an open biopsy was performed immediately. Microscopically, numerous amoebic trophozoites, measuring 20 to 25 µm in size, with nuclei containing one to four nucleoli and some scattered cysts having a double-layered wall were noted in the background of hemorrhagic necrosis. Based on the microscopic findings, amoebic encephalitis caused by Balamuthia mandrillaris was diagnosed. The patient died on the 10th day after being admitted at the hospital. The diagnosis of amoebic encephalitis in the early stage is difficult for clinicians. Moreover, most cases undergo rapid deterioration, resulting in fatal consequences. In this report, we present the first case of B. mandrillaris amoebic encephalitis with fatal progression in a Korean patient.
Diffuse Involvement of Primary Colorectal Lymphoma Simulating Ulcerative Colitis
Ji-Ye Kim, Sun Hee Chang, Han Seong Kim, Mee Joo
J Pathol Transl Med. 2019;53(5):332-336.   Published online August 2, 2019
DOI: https://doi.org/10.4132/jptm.2019.07.12
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AbstractAbstract PDF
Diffuse involvement of colorectal lymphoma masquerading as colitis is a very rare presentation of primary colorectal lymphoma. Detecting occult lymphoma is difficult in the setting of diffuse colonic involvement with no definite mass and inflammatory mucosal changes. We encountered a case of diffuse-type primary colorectal lymphoma simulating ulcerative colitis in a previously healthy 31-year-old woman. Despite multiple mucosal biopsies, the biopsy diagnosis was not made due to unawareness of atypical lymphocytes admixed with dense lymphoplasmacytic infiltration. The present case emphasizes the importance of being aware of this rare presentation of primary colorectal lymphoma in order to avoid misdiagnosis.
Brief Case Reports
Human Papillomavirus–Related Multiphenotypic Sinonasal Carcinoma with Late Recurrence
Bokyung Ahn, Eojin Kim, Harim Oh, Yang-Seok Chae, Chul Hwan Kim, Youngseok Lee, Jeong Hyeon Lee, Yoo Jin Lee
J Pathol Transl Med. 2019;53(5):337-340.   Published online April 25, 2019
DOI: https://doi.org/10.4132/jptm.2019.04.02
  • 3,636 View
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  • 6 Citations
PDF
Liquid-Based Cytology Features of Papillary Squamotransitional Cell Carcinoma of the Uterine Cervix
Yangkyu Lee, Younghwa Choi, Kiryang Lee, Youngeun Lee, Hyojin Kim, Ji-Young Choe, Hye Seung Lee, Yong Beom Kim, Haeryoung Kim
J Pathol Transl Med. 2019;53(5):341-344.   Published online June 24, 2019
DOI: https://doi.org/10.4132/jptm.2019.06.05
  • 3,478 View
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  • 1 Citations
PDF
Retraction
RETRACTION: eNOS Gene Polymorphisms in Perinatal Hypoxic-Ischemic Encephalopathy
J Pathol Transl Med. 2019;53(5):345-345.   Published online September 6, 2019
DOI: https://doi.org/10.4132/jptm.2019.09.06
Retracts: J Pathol Transl Med 2009;43(4):306
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  • 2 Citations
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JPTM : Journal of Pathology and Translational Medicine