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Volume 52(6); November 2018
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Letter to the Editor
Alveolar Squamous Cell Metaplasia: Preneoplastic Lesion?
Adriana Handra-Luca
J Pathol Transl Med. 2018;52(6):355-356.   Published online October 1, 2018
DOI: https://doi.org/10.4132/jptm.2018.09.07
  • 3,386 View
  • 101 Download
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Original Articles
The Expression of Adipophilin Is Frequently Found in Solid Subtype Adenocarcinoma and Is Associated with Adverse Outcomes in Lung Adenocarcinoma
Sun Ah Shin, Hee Young Na, Ji Young Choe, Doohyun Chung, Mira Park, Sohee Oh, Ji Eun Kim
J Pathol Transl Med. 2018;52(6):357-362.   Published online October 4, 2018
DOI: https://doi.org/10.4132/jptm.2018.09.13
  • 3,866 View
  • 98 Download
  • 2 Citations
AbstractAbstract PDF
Background
The up-regulation of the lipogenic pathway has been reported in many types of malignant tumors. However, its pathogenic role or clinical significance is not fully understood. The objective of this study was to examine the expression levels of adipophilin and related hypoxic signaling proteins and to determine their prognostic impacts and associations with the pathologic characteristics of lung adenocarcinoma.
Methods
Expression levels of adipophilin, heat shock protein 27 (HSP27), carbonic anhydrase IX, and hypoxia-inducible factor 1α were examined by immunohistochemical staining using tissue microarray blocks. Correlations between protein expression levels and various clinicopathologic features were analyzed.
Results
A total of 230 cases of primary adenocarcinoma of the lung were enrolled in this study. Adipophilin expression was more frequent in males and with the solid histologic type. It was correlated with HSP27 expression. Patients with adipophilin-positive adenocarcinoma showed a shorter progression-free survival (PFS) (median PFS, 17.2 months vs 18.4 months) in a univariable survival analysis, whereas HSP27 positivity correlated with favorable overall survival (OS) and PFS. In a multivariable analysis, adipophilin and HSP27 were independent prognostic markers of both OS and PFS.
Conclusions
Activated lipid metabolism and the hypoxic signaling pathway might play a major role in the progression of lung adenocarcinoma, especially in the solid histologic type.
Immunohistochemistry of Janus Kinase 1 (JAK1) Expression in Vitiligo
Asmaa Gaber Abdou, Alaa Maraee, Hossam Yassien, Mona Sarhan
J Pathol Transl Med. 2018;52(6):363-368.   Published online October 23, 2018
DOI: https://doi.org/10.4132/jptm.2018.09.18
  • 7,674 View
  • 174 Download
  • 7 Citations
AbstractAbstract PDF
Background
Vitiligo is a chronic autoimmune disease in which the destruction of melanocytes causes white spots on the affected skin. Janus kinase (JAK) is a family of intracellular, non-receptor tyrosine kinases that transduce cytokine-mediated signals via the JAK–signal transducer and activator of transcription pathway. The aim of the present study is to explore the possible role of JAK1 in the pathogenesis of vitiligo using immunohistochemical methods.
Methods
The current study was conducted in a sample of 39 patients who presented with vitiligo and 22 healthy individuals who were age and sex matched as a control group. We used immunohistochemistry to evaluate JAK1 status (intensity and distribution) and assess the percentage of residual melanocytes using human melanoma black 45 (HMB45).
Results
Intense and diffuse JAK1 expression was significantly more likely to indicate vitiliginous skin compared to normal skin (p < .001). Strong and diffuse JAK1 expression was associated with short disease duration, female sex, and lower percentage of melanocytes (detected by HMB45) (p < .05).
Conclusions
JAK1 may be involved in the pathogenesis of vitiligo, as indicated by intense and diffuse expression compared to control and association with lower percentage of melanocytes detected by HMB45 immunostaining.
High Cytoplasmic CXCR4 Expression Predicts Prolonged Survival in Triple-Negative Breast Cancer Patients Treated with Adjuvant Chemotherapy
Bobae Shim, Min‐Sun Jin, Ji Hye Moon, In Ae Park, Han Suk Ryu
J Pathol Transl Med. 2018;52(6):369-377.   Published online October 1, 2018
DOI: https://doi.org/10.4132/jptm.2018.09.19
  • 10,489 View
  • 149 Download
  • 6 Citations
AbstractAbstract PDF
Background
Chemokine receptor CXC chemokine receptor type 4 (CXCR4) and its ligand CXC motif chemokine 12 (CXCL12; stromal cell-derived factor-1) are implicated in tumor growth, metastasis, and tumor cell-microenvironment interaction. A number of studies have reported that increased CXCR4 expression is associated with worse prognosis in triple-negative breast cancer (TNBC), but its prognostic significance has not been studied in TNBC patients treated with adjuvant chemotherapy.
Methods
Two hundred eighty-three TNBC patients who received adjuvant chemotherapy were retrospectively analyzed. Tissue microarray was constructed from formalinfixed, paraffin-embedded tumor tissue and immunohistochemistry for CXCR4 and CXCL12 was performed. Expression of each marker was compared with clinicopathologic characteristics and outcome.
Results
High cytoplasmic CXCR4 expression was associated with younger age (p = .008), higher histologic grade (p = .007) and lower pathologic stage (p = .045), while high CXCL12 expression was related to larger tumor size (p = .045), positive lymph node metastasis (p = .005), and higher pathologic stage (p = .017). The patients with high cytoplasmic CXCR4 experienced lower distant recurrence (p = .006) and better recurrence-free survival (RFS) (log-rank p = .020) after adjuvant chemotherapy. Cytoplasmic CXCR4 expression remained an independent factor of distant recurrence (p = .019) and RFS (p = .038) after multivariate analysis.
Conclusions
High cytoplasmic CXCR4 expression was associated with lower distant recurrence and better RFS in TNBC patients treated with adjuvant chemotherapy. This is the first study to correlate high CXCR4 expression to better TNBC prognosis, and the underlying mechanism needs to be elucidated in further studies.
Loss of Nuclear BAP1 Expression Is Associated with High WHO/ISUP Grade in Clear Cell Renal Cell Carcinoma
Young Chan Wi, Ahrim Moon, Min Jung Jung, Yeseul Kim, Seong Sik Bang, Kiseok Jang, Seung Sam Paik, Su-Jin Shin
J Pathol Transl Med. 2018;52(6):378-385.   Published online October 1, 2018
DOI: https://doi.org/10.4132/jptm.2018.09.21
  • 5,802 View
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  • 9 Citations
AbstractAbstract PDF
Background
BRCA1-associated protein 1 (BAP1) mutations are frequently reported in clear cell renal cell carcinoma (ccRCC); however, very few studies have evaluated the role of these mutations in other renal cell carcinoma (RCC) subtypes. Therefore, we analyzed BAP1 protein expression using immunohistochemistry in several RCC subtypes and assessed its relationship with clinicopathological characteristics of patients.
Methods
BAP1 expression was immunohistochemically evaluated in tissue microarray blocks constructed from 371 samples of RCC collected from two medical institutions. BAP1 expression was evaluated based on the extent of nuclear staining in tumor cells, and no expression or expression in < 10% of tumor cells was defined as negative.
Results
Loss of BAP1 expression was observed in ccRCC (56/300, 18.7%), chromophobe RCC (6/26, 23.1%), and clear cell papillary RCC (1/4, 25%), while we failed to detect BAP1 expression loss in papillary RCC, acquired cystic disease-associated RCC, or collecting duct carcinoma. In ccRCC, loss of BAP1 expression was significantly associated with high World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grade (p = .002); however, no significant correlation was observed between loss of BAP1 expression and survival in ccRCC. Loss of BAP1 expression showed no association with prognostic factors in chromophobe RCC.
Conclusions
Loss of BAP1 nuclear expression was observed in both ccRCC and chromophobe RCC. In addition, BAP1 expression loss was associated with poor prognostic factors such as high WHO/ISUP grade in ccRCC.
Multiplicity of Advanced T Category–Tumors Is a Risk Factor for Survival in Patients with Colorectal Carcinoma
Hye Eun Park, Seungyeon Yoo, Jeong Mo Bae, Seorin Jeong, Nam-Yun Cho, Gyeong Hoon Kang
J Pathol Transl Med. 2018;52(6):386-395.   Published online November 14, 2018
DOI: https://doi.org/10.4132/jptm.2018.10.02
  • 3,597 View
  • 53 Download
  • 2 Citations
AbstractAbstract PDF
Background
Previous studies on synchronous colorectal carcinoma (SCRC) have reported inconsistent results about its clinicopathologic and molecular features and prognostic significance.
Methods
Forty-six patients with multiple advanced tumors (T2 or higher category) who did not receive neoadjuvant chemotherapy and/or radiotherapy and who are not associated with familial adenomatous polyposis were selected and 99 tumors from them were subjected to clinicopathologic and molecular analysis. Ninety-two cases of solitary colorectal carcinoma (CRC) were selected as a control considering the distributions of types of surgeries performed on patients with SCRC and T categories of individual tumors from SCRC.
Results
SCRC with multiple advanced tumors was significantly associated with more frequent nodal metastasis (p = .003) and distant metastasis (p = .001) than solitary CRC. KRAS mutation, microsatellite instability, and CpG island methylator phenotype statuses were not different between SCRC and solitary CRC groups. In univariate survival analysis, overall and recurrence-free survival were significantly lower in patients with SCRC than in patients with solitary CRC, even after adjusting for the extensiveness of surgical procedure, adjuvant chemotherapy, or staging. Multivariate Cox regression analysis revealed that tumor multiplicity was an independent prognostic factor for overall survival (hazard ratio, 4.618; 95% confidence interval, 2.126 to 10.030; p < .001), but not for recurrence-free survival (p = .151).
Conclusions
Findings suggested that multiplicity of advanced T category–tumors might be associated with an increased risk of nodal metastasis and a risk factor for poor survival, which raises a concern about the guideline of American Joint Committee on Cancer’s tumor-node-metastasis staging that T staging of an index tumor determines T staging of SCRC.
The Prognostic Impact of Synchronous Ipsilateral Multiple Breast Cancer: Survival Outcomes according to the Eighth American Joint Committee on Cancer Staging and Molecular Subtype
Jinah Chu, Hyunsik Bae, Youjeong Seo, Soo Youn Cho, Seok-Hyung Kim, Eun Yoon Cho
J Pathol Transl Med. 2018;52(6):396-403.   Published online October 23, 2018
DOI: https://doi.org/10.4132/jptm.2018.10.03
  • 4,281 View
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  • 5 Citations
AbstractAbstract PDF
Background
In the current American Joint Committee on Cancer staging system of breast cancer, only tumor size determines T-category regardless of whether the tumor is single or multiple. This study evaluated if tumor multiplicity has prognostic value and can be used to subclassify breast cancer.
Methods
We included 5,758 patients with invasive breast cancer who underwent surgery at Samsung Medical Center, Seoul, Korea, from 1995 to 2012.
Results
Patients were divided into two groups according to multiplicity (single, n = 4,744; multiple, n = 1,014). Statistically significant differences in lymph node involvement and lymphatic invasion were found between the two groups (p < .001). Patients with multiple masses tended to have luminal A molecular subtype (p < .001). On Kaplan-Meier survival analysis, patients with multiple masses had significantly poorer disease-free survival (DFS) (p = .016). The prognostic significance of multiplicity was seen in patients with anatomic staging group I and prognostic staging group IA (p = .019 and p = .032, respectively). When targeting patients with T1-2 N0 M0, hormone receptor–positive, and human epidermal growth factor receptor 2 (HER2)–negative cancer, Kaplan-Meier survival analysis also revealed significantly reduced DFS with multiple cancer (p = .031). The multivariate analysis indicated that multiplicity was independently correlated with worse DFS (hazard ratio, 1.23; 95% confidence interval, 1.03 to 1.47; p = .025). The results of this study indicate that tumor multiplicity is frequently found in luminal A subtype, is associated with frequent lymph node metastasis, and is correlated with worse DFS.
Conclusions
Tumor multiplicity has prognostic value and could be used to subclassify invasive breast cancer at early stages. Adjuvant chemotherapy would be necessary for multiple masses of T1–2 N0 M0, hormone-receptor-positive, and HER2-negative cancer.
The Usefulness of Immunocytochemistry of CD56 in Determining Malignancy from Indeterminate Thyroid Fine-Needle Aspiration Cytology
Hyunseo Cha, Ju Yeon Pyo, Soon Won Hong
J Pathol Transl Med. 2018;52(6):404-410.   Published online October 15, 2018
DOI: https://doi.org/10.4132/jptm.2018.09.20
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  • 1 Citations
AbstractAbstract PDF
Background
Fine-needle aspiration cytology serves as a safe, economical tool in evaluating thyroid nodules. However, about 30% of the samples are categorized as indeterminate. Hence, many immunocytochemistry markers have been studied, but there has not been a single outstanding marker. We studied the efficacy of CD56 with human bone marrow endothelial cell marker-1 (HBME-1) in diagnosis in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) category III.
Methods
We reviewed ThinPrep liquid-based cytology (LBC) samples with Papanicolaou stain from July 1 to December 31, 2016 (2,195 cases) and selected TBSRTC category III cases (n = 363). Twenty-six cases were histologically confirmed as benign (six cases, 23%) or malignant (20 cases, 77%); we stained 26 LBC slides with HBME-1 and CD56 through the cell transfer method. For evaluation of reactivity of immunocytochemistry, we chose atypical follicular cell clusters.
Results
CD56 was not reactive in 18 of 20 cases (90%) of malignant nodules and showed cytoplasmic positivity in five of six cases (83%) of benign nodules. CD56 showed high sensitivity (90.0%) and relatively low specificity (83.3%) in detecting malignancy (p = .004). HBME-1 was reactive in 17 of 20 cases (85%) of malignant nodules and was not reactive in five of six cases (83%) of benign nodules. HBME-1 showed slightly lower sensitivity (85.0%) than CD56. The specificity in detecting malignancy by HBME-1 was similar to that of CD56 (83.3%, p = .008). CD56 and HBME-1 tests combined showed lower sensitivity (75.0% vs 90%) and higher specificity (93.8% vs 83.3%) in detecting malignancy compared to using CD56 alone.
Conclusions
Using CD56 alone showed relatively low specificity despite high sensitivity for detecting malignancy. Combining CD56 with HBME-1 could increase the specificity. Thus, we suggest that CD56 could be a useful preoperative marker for differential diagnosis of TBSRTC category III samples.
Case Studies
Squamous Metaplasia in Pleomorphic Adenoma: A Diagnostic and Prognostic Enigma
Swati Sharma, Monica Mehendiratta, Nivedita Chaudhary, Vineet Gupta, Maulshree Kohli, Anjana Arora
J Pathol Transl Med. 2018;52(6):411-415.   Published online October 1, 2018
DOI: https://doi.org/10.4132/jptm.2018.07.15
  • 4,646 View
  • 108 Download
  • 9 Citations
AbstractAbstract PDF
Pleomorphic adenoma (PA) is the most common benign salivary gland tumor. Histologically, squamous metaplasia has been reported in PA, but has rarely been documented as being extensive enough to cause significant misdiagnosis. Here, we present an unusual case of PA in a 50-year-old female patient presenting with swelling on the postero-lateral aspect of the palate for a week. Histopathologically, the tumor exhibited the features of conventional PA with extensive squamous metaplasia and giant keratotic lamellae in cyst-like areas. Such exuberant squamous metaplasia and keratin can be a diagnostic and prognostic pitfall and lead to overtreatment of the patient.
An Intrarenal Adrenocortical Carcinoma Arising in an Adrenal Rest
Ji Hee Lee, Young Deuk Choi, Nam Hoon Cho
J Pathol Transl Med. 2018;52(6):416-419.   Published online October 1, 2018
DOI: https://doi.org/10.4132/jptm.2018.07.20
  • 4,052 View
  • 80 Download
  • 3 Citations
AbstractAbstract PDF
We describe a case of a 61-year-old Korean man who was diagnosed with renal cell carcinoma that was discovered on abdominopelvic computed tomography obtained after the patient complained of back pain. A radical nephrectomy was performed, and the surgical specimen showed a relatively well-circumscribed and yellowish lobulated hard mass. Microscopically, the tumor showed sheets and nests of hypercellular pleomorphic cells with thick fibrous septation, frequent mitoses, and areas of adrenal cortical-like tissue. Immunohistochemical staining revealed that the tumor cells were positive for inhibin-α, vimentin, synaptophysin, and melan A. It also revealed that the tumor cells were negative for pan-cytokeratin, epithelial membrane antigen, paired box 8, α-methylacyl-coenzyme A racemase, CD10, cytokeratin 7, carbonic anhydrase 9, c-Kit, renal cell carcinoma, transcription factor E3, human melanoma black 45, desmin, smooth muscle actin, S-100, chromogranin A, CD34, anaplastic lymphoma kinase, and integrase interactor 1. Based on these histopathological and immunohistochemical findings, we diagnosed the tumor as intrarenal adrenocortical carcinoma arising in an adrenal rest. Several cases of intrarenal adrenocortical carcinoma have been reported, although they are very rare. Due to its poor prognosis and common recurrence or metastasis, clinicians and pathologists must be aware of this entity.
Brief Case Reports
Collagenous Spherulosis Associated with Lobular Carcinoma In Situ of the Breast: Two Case Reports
Ga-Eon Kim, Nah Ihm Kim, Ji Shin Lee, Min Ho Park
J Pathol Transl Med. 2018;52(6):420-424.   Published online March 29, 2018
DOI: https://doi.org/10.4132/jptm.2018.03.29
  • 4,353 View
  • 128 Download
  • 1 Citations
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Follicular T-Cell Lymphoma with Concomitant Lennert Lymphoma
Seungkyu Choi, Jai-Hyang Go
J Pathol Transl Med. 2018;52(6):425-427.   Published online July 16, 2018
DOI: https://doi.org/10.4132/jptm.2018.04.16
  • 4,680 View
  • 126 Download
  • 1 Citations
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JPTM : Journal of Pathology and Translational Medicine