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Extranodal NK/T cell lymphoma, nasal type: a rare diagnosis with common nasal presentation

Mohd Ramli SS, Husain S, Wong YP

BMJ Case Rep, 2021 Jun 22;14(6).
PMID: 34158320 DOI: 10.1136/bcr-2020-236436

A 39-year-old man presented with bilateral nasal obstruction for 4 months and associated with hyposmia and foul-smelling nasal discharge. Nasal endoscopy showed irregular mucosa of the nasal cavity with easily bleeding. Nasal biopsy reported as extranodal Natural Killer/T cell lymphoma, nasal type. In-situ hybridisation for Epstein-Barr encoding region was positive. He was treated with six cycles of gemcitabine, oxaliplatin and L-asparaginase and peripheral blood stem cell transplant. After the treatment, he was asymptomatic until 9 months where he had splenic abscess and undergone splenectomy. He was asymptomatic of the disease for 2 years.
Cervical angiomyofibroblastoma: a case report and review of literature

Wong YP, Tan GC, Ng PF

J Obstet Gynaecol, 2017 Jul;37(5):681-682.
PMID: 28604180 DOI: 10.1080/01443615.2017.1281236
Xanthomatous meningioma: A metaplastic or degenerative phenomenon?

Wong YP, Tan GC, Kumar R

Neuropathology, 2018 Dec;38(6):619-623.
PMID: 30187570 DOI: 10.1111/neup.12511

Xanthomatous changes can be observed in various conditions including primary xanthomatosis that is linked to an underlying hypercholesterolemia and more commonly associated with secondary xanthomatous degenerative processes in neoplasm and chronic inflammation. Meningioma with extensive xanthomatous change is exceedingly rare. The presence of cholesterol clefts within this peculiar meningioma subtype has not been described. Herein, we report an unusual case of xanthomatous meningioma in an 83-year-old normolipidemic woman, who presented to us with worsening lower limb weakness and global aphasia. There was increasing evidence to suggest that the presence of xanthomatous changes in long-standing meningioma is merely a sequela of cellular degeneration rather than true metaplastic change as previously hypothesized. Hence, the diagnosis of "xanthomatous meningioma" in the metaplastic category should be revisited and considered as a distinct histological subtype. The possible histogenesis of such intriguing phenomenon is discussed with a review of the literature.
CD3-positive plasmablastic lymphoma reported in two cases: A potential diagnostic caveat

Wong YP, Masir N, Chew MX

Indian J Pathol Microbiol, 2021 8 4;64(3):579-583.
PMID: 34341278 DOI: 10.4103/IJPM.IJPM_616_20

Plasmablastic lymphoma (PBL) is a rare aggressive subtype of mature large B cell lymphoma involving almost exclusively the extranodal regions particularly the oral cavity, frequently described in immunocompromised patients. PBL is characterized histologically by diffuse proliferation of large neoplastic cells resembling B immunoblasts or plasmablasts. The diagnosis of PBL can be difficult due to its ambiguous histopathological features mimicking most large cell lymphomas and lacking a distinctive immunophenotypic pattern. They typically lack expression of CD20 and CD79a but may express plasma cell marker, CD138. Aberrant immunoexpression of CD3, a T-cell marker in PBL in the absence of other B-cell markers is exceptionally rare, may potentially lead to incorrect interpretation. Herein, we report a case series of CD3-positive PBL of oral cavity in two individuals, which were initially misdiagnosed as high-grade T-cell lymphomas including extranodal NK/T-cell lymphoma, nasal type. Useful distinguishing clinical settings, histomorphological features, immunohistochemistry and molecular expression profiles of PBL are discussed.
Fulltext SARS-CoV-2 Transplacental Transmission: A Rare Occurrence? An Overview of the Protective Role of the Placenta

Wong YP, Tan GC, Khong TY

Int J Mol Sci, 2023 Feb 25;24(5).
PMID: 36901979 DOI: 10.3390/ijms24054550

The outbreak of the coronavirus disease 2019 (COVID-19) pandemic, caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global public health crisis, causing substantial concern especially to the pregnant population. Pregnant women infected with SARS-CoV-2 are at greater risk of devastating pregnancy complications such as premature delivery and stillbirth. Irrespective of the emerging reported cases of neonatal COVID-19, reassuringly, confirmatory evidence of vertical transmission is still lacking. The protective role of the placenta in limiting in utero spread of virus to the developing fetus is intriguing. The short- and long-term impact of maternal COVID-19 infection in the newborn remains an unresolved question. In this review, we explore the recent evidence of SARS-CoV-2 vertical transmission, cell-entry pathways, placental responses towards SARS-CoV-2 infection, and its potential effects on the offspring. We further discuss how the placenta serves as a defensive front against SARS-CoV-2 by exerting various cellular and molecular defense pathways. A better understanding of the placental barrier, immune defense, and modulation strategies involved in restricting transplacental transmission may provide valuable insights for future development of antiviral and immunomodulatory therapies to improve pregnancy outcomes.
Fulltext Can we confidently diagnose pilomatricoma with fine needle aspiration cytology?

Wong YP, Masir N, Sharifah NA

Malays J Med Sci, 2015 Jan-Feb;22(1):84-8.
PMID: 25892955 MyJurnal

Pilomatricomas can be confidently diagnosed cytologically due to their characteristic cytomorphological features. However, these lesions are rarely encountered by cytopathologists and thus pose a diagnostic dilemma to even experienced individuals, especially when the lesions are focally sampled. We describe two cases of histologically confirmed pilomatricoma. The first case is of a 13-year-old boy with posterior cervical 'lymphadenopathy', and the second one is of a 12-year-old girl with a lower cheek swelling. Both aspirates comprised predominantly atypical basal-like cells, with prominent nucleoli. 'Ghost cells' were readily identified by cell block in case two, but cell block in case one yielded no diagnostic material. In case two, pilomatricoma was accurately diagnosed pre-operatively. A cytological suspicion of a neoplastic process was raised in case one. Despite being diagnostically challenging, pilomatricoma can be diagnosed with careful observation of two unique cytological features of the lesions: (1) pathognomonic 'ghost cells' and (2) irregular, saw-toothed, loosely cohesive basaloid cells, with prominent nucleoli. The role of thorough sampling of the lesion, with multiple passes of various sites, cannot be overemphasized.
The value of umbilical cord insertion site sampling in detecting maternal and/or fetal inflammatory response

Wong YP, Tan GC, Khong TY

APMIS, 2025 Jan;133(1):e13496.
PMID: 39509086 DOI: 10.1111/apm.13496

The 2016 Amsterdam Placental Workshop Group Consensus Statement recommends sampling a block of the placenta close to the umbilical cord insertion site (UCIB) for histopathological evaluation. This piece of placenta at the umbilical cord insertion is presumed to give a better yield of inflammation (if present). We aimed to investigate the utility of the UCIB in the detection of maternal and/or fetal inflammatory responses (MIR and/or FIR), in comparison with the other sections of the placental parenchyma. This is a retrospective cross-sectional study including all placentas with histologic chorioamnionitis. The histopathological slides of placentas were reviewed as per Amsterdam consensus guidelines. Diagnostic performance of UCIB in identifying MIR and/or FIR, relative to the other placental sections, was assessed. UCIB revealed diagnostic sensitivity, specificity, and diagnostic accuracy of 79.2% (95% CI: 74.2-83.6%), 100.0% (95% CI: 95.6-100.0%), and 83.6% (95% CI: 79.5-87.2%), respectively, in the detection of FIR, while showing a low sensitivity of 52.6% (95% CI: 47.5-57.6%) in detecting MIR. In 59 (24.6%) cases, FIR was not seen in the corresponding placental parenchymal sections but was detected in the UCIBs. This study is the first study to confirm that a section from the UCIB is essential for the detection of FIR, which affirms the Amsterdam consensus sampling recommendations.
Fulltext A case of t(14; 18)-negative follicular lymphoma with atypical immunophenotype: usefulness of immunoarchitecture of Ki67, CD79a and follicular dendritic cell meshwork in making the diagnosis

Wong Y, Abdul-Rahman F, Samsudin AT, Masir N

Malays J Pathol, 2014 Aug;36(2):125-9.
PMID: 25194535 MyJurnal

Follicular lymphoma is characterised by the t(14;18)(q32;q21) chromosomal translocation causing BCL2 protein overexpression. A proportion of follicular lymphomas do not carry the t(14;18) translocation and lacked BCL2 protein expression. We describe a case of a BCL2 protein- and t(14;18)-negative follicular lymphoma that caused diagnostic difficulty. The usefulness of several immunomarkers including Ki67, CD79a and CD21 in aiding the diagnosis is discussed. The patient is a 51-year-old male who presented with gradually enlarging lymphadenopathy. Histopathological examination of the lymph node showed complete architectural effacement by neoplastic follicles containing expanded CD21-positive follicular dendritic cell meshwork. The neoplastic cells expressed pan-B cell markers (CD20, CD79a) and germinal centre marker (BCL6) but not BCL2 and CD10. Of interest are the staining patterns of Ki67 and CD79a. We observed that the Ki67- positive proliferating cells were evenly distributed within the neoplastic follicles without zonation. In addition, CD79a was homogeneously strong within the neoplastic follicles. These staining patterns were distinctly different from that observed in reactive lymphoid follicles. Fluorescent insitu hybridisation (FISH) analysis however showed absence of BCL2 gene rearrangement. Despite the atypical immunophenotype and lack of BCL2 gene rearrangement, the diagnosis of follicular lymphoma was made based on careful observation of the morphology as well as immunoarchitecture of the Ki67, CD79a and CD21 markers.
Diagnostic Value of the EZH2 Immunomarker in Malignant Effusion Cytology

Ang PP, Tan GC, Karim N, Wong YP

Acta Cytol., 2020;64(3):248-255.
PMID: 31352449 DOI: 10.1159/000501406

BACKGROUND: Differentiating reactive mesothelial cells from metastatic carcinoma in effusion cytology is a challenging task. The application of at least 4 monoclonal antibodies including 2 epithelial markers (Ber-EP4, MOC-31, CEA, or B72.3) and 2 mesothelial markers (calretinin, WT-1, CK5/6, or HBME-1) are often useful in this distinction; however, it is not readily available in many resource-limited developing countries. Aberrant immunoexpression of enhancer of zeste homolog 2 (EZH2), a transcriptional repressor involved in cancer progression, is observed widely in various malignancy. In this study, we evaluate the diagnostic value of EZH2 as a single reliable immunomarker for malignancy in effusion samples.
METHODS: A total of 108 pleural, peritoneal, and pericardial effusions/washings diagnosed as unequivocally reactive (n = 41) and metastatic carcinoma (n = 67) by cytomorphology over 18 months were reviewed. Among the metastatic carcinoma cases, 54 were adenocarcinoma and others were squamous cell carcinoma (n = 1), carcinosarcoma (n = 1), and carcinoma of undefined histological subtypes (n = 11). Cell block sections were immunostained by EZH2 (Cell Marque, USA). The percentages of EZH2-immunolabeled cells over the total cells of interest were calculated. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off score to define EZH2 immunopositivity.
RESULTS: A threshold of 8% EZH2-immunolabeled cells allows distinction between malignant and reactive mesothelial cells, with 95.5% sensitivity, 100% specificity, 100% positive predictive value, and 93.2% negative predictive value (p < 0.0001). The area under the curve was 0.988.
CONCLUSION: EZH2 is a promising diagnostic biomarker for malignancy in effusion cytology which is inexpensive yet trustworthy and could potentially be used routinely in countries under considerable economic constraints.
Heterotopic ossification in psammomatous spinal meningioma: a diagnostic controversy

Wong YP, Tan GC, Mukari SAM, Palaniandy K

Int J Clin Exp Pathol, 2021;14(5):627-632.
PMID: 34093948

Heterotopic ossification (HO), a synonym for osseous metaplasia, is a pathological phenomenon, characterized by abnormal bone formation outside the skeletal system observed commonly in various neoplastic and non-neoplastic diseases. HO occurring in meningioma is exceptionally rare. We reportherein an unusual case of spinal meningioma containing numerous calcified psammoma bodies and extensive HO in a 75-year-old woman, who presented with progressive worsening bilateral lower limb weakness and numbness. The presence of remarkable bone formation within a meningioma is controversial among pathologists; while some regard them as psammomatous meningioma as the primary diagnosis, others prefer osteoblastic meningioma, a form of metaplastic meningioma. There is compelling molecular data to advocate that HO is an active disease process involving metaplastic (osseous) differentiation of meningioma stroma mesenchymal stem-like cells, but not the meningothelial-derived tumor cells. Henceforth, the term "metaplastic meningioma" may not be appropriate in this context. A plausible designation as "psammomatous meningioma with osseous metaplasia" defines this entity more accurately. This paper highlights the need for a unifying nomenclature to reduce diagnostic controversy caused by conflicting terms in the literature. The possible pathogenesis of this intriguing phenomenon is discussed.
Fulltext Paratesticular aggressive angiomyxoma: A rare case

Ismail MI, Wong YP, Tan GH, Fam XI

Urol Ann, 2017 5 10;9(2):197-199.
PMID: 28479778 DOI: 10.4103/UA.UA_168_16

Aggressive angiomyxoma (AAM) particularly testicular origin is a rare benign mesenchymal myxoid tumor which is locally aggressive, blatant for local recurrence, and may metastasize. It occurs mostly in females of childbearing age and extremely rare in males. AMM particular testicular origin is not reported in literature yet. This is a 65-year-old man who had a right scrotal swelling. Ultrasound scrotum showed a soft tissue tumor of the right testis. The patient underwent radical right orchidectomy of which histopathologically confirmed to be a paratesticular AAM with clear resection margins. There were no signs of local recurrence or metastasis 2 years postsurgical resection.
Fulltext Metastasis within a metastasis to the thyroid: A rare phenomenon

Wong YP, Affandi KA, Tan GC, Muhammad R

Indian J Pathol Microbiol, 2017 9 25;60(3):430-432.
PMID: 28937391 DOI: 10.4103/IJPM.IJPM_287_16

Metastatic disease involving the thyroid gland is uncommon. Solitary thyroid metastases from various primary sites particularly kidney, lung, and breast had been previously described. To the best of our knowledge, metastases from two topographically separate primary malignancies to the thyroid have never been documented hitherto. This is the first reported case of cancer-to-cancer metastasis involving an invasive breast carcinoma metastasized within a metastatic renal cell carcinoma in the nonneoplastic thyroid in a 58-year-old woman. Distinguishing a secondary thyroid metastases from a primary thyroid malignancy is utmost crucial as treatment differs. The possibility of tumor metastases from two separated primaries should always be considered in a tumor exhibiting malignant cell populations with two distinctive histomorphological appearances. The role of immunohistochemistry stains in equivocal cases cannot be overemphasized.
Fulltext Beta-human Chorionic Gonadotropin-secreting Lung Adenocarcinoma

Wong YP, Tan GC, Aziz S, Pongprakyun S, Ismail F

Malays J Med Sci, 2015 Jul-Aug;22(4):76-80.
PMID: 26715912 MyJurnal

Overexpression of beta-human chorionic gonadotropin (β-hCG) is frequently associated with germ cell tumours, especially choriocarcinoma. Ectopic secretion of β-hCG by non-small cell lung cancer is exceptional. We present an exceedingly rare case of pulmonary adenocarcinoma that secretes β-hCG. Our patient is a 62-year-old postmenopausal woman, a nonsmoker, who presented with a six-month history of progressive dyspnoea, associated with decreased appetite and significant weight loss. Her serum β-hCG was very high (11211.9 mIU/ml), which prompted investigations to exclude germ cell tumour. Radiological imaging revealed a 10-cm right lung mass with adrenal metastasis. No other focal lesions were detected. Microscopy of the lung biopsy specimen showed replacement of normal lung tissue by sheets of malignant cells, forming vague glands in some areas. Immunohistochemically, the malignant cells showed focal immunopositivity for thyroid transcription factor 1 (TTF-1), napsin A, cytokeratin 7 (CK7) and β-hCG. A diagnosis of β-hCG-secreting pulmonary poorly differentiated adenocarcinoma was rendered. Serum β-hCG level decreased significantly to 168.6 mIU/ml after the first cycle of chemotherapy. In conclusion, β-hCG expression in lung cancer should be recognised to facilitate prompt diagnosis and initiation of appropriate intervention.
Dendritic fibromyxolipoma: a variant of spindle cell lipoma with extensive myxoid change, with cytogenetic evidence

Wong YP, Chia WK, Low SF, Mohamed-Haflah NH, Sharifah NA

Pathol. Int., 2014 Jul;64(7):346-51.
PMID: 25047505 DOI: 10.1111/pin.12176

Dendritic fibromyxolipoma (DFML), a rare, recently described distinct benign soft tissue tumor, has many clinicopathological features reminiscent of spindle cell lipoma and solitary fibrous tumor with myxoid change. It is distinguished histologically from both entities by the presence of spindle and stellate cells with dendritic cytoplasmic prolongations, prominent myxoid stroma with abundant keloidal collagen and occasional small plexiform vascular proliferation. We describe a case of histologically confirmed DFML of the left shoulder in a 67-year-old male, in which subsequent cytogenetic analysis revealed deletion involving 13q14.3 region in all the tumor cells, typically detected in spindle cell lipoma. In the presence of many clinicopathological similarities between DFML and spindle cell lipoma including chromosomal abnormalities, we postulate that DFML is merely a rare variant of spindle cell lipoma with extensive myxoid degeneration, and may not be considered as a separate entity. The possible differential diagnosis and their distinguishing features are briefly discussed.
Comparative analysis between multilevel sectioning with conventional haematoxylin and eosin staining and immunohistochemistry for detecting nodal micrometastases with stage I and II colorectal cancers

Wong YP, Shah SA, Shaari N, Mohamad Esa MS, Sagap I, Isa NM

Asian Pac J Cancer Prev, 2014;15(4):1725-30.
PMID: 24641399

Management of patients with stage II colorectal carcinomas remains challenging as 20 - 30% of them will develop recurrence. It is postulated that these patients may harbour nodal micrometastases which are imperceptible by routine histopathological evaluation. The aims of our study were to evaluate (1) the feasibility of multilevel sectioning method utilizing haematoxylin and eosin stain and immunohistochemistry technique with cytokeratin AE1/AE3, in detecting micrometastases in histologically-negative lymph nodes, and (2) correlation between nodal micrometastases with clinicopathological parameters. Sixty two stage I and II cases with a total of 635 lymph nodes were reviewed. Five-level haematoxylin and eosin staining and one-level cytokeratin AE1/AE3 immunostaining were performed on all lymph nodes retrieved. The findings were correlated with clinicopathological parameters. Two (3.2%) lymph nodes in two patients (one in each) were found to harbour micrometastases detected by both methods. With cytokeratin AE1/AE3, we successfully identified four (6.5%) patients with isolated tumour cells, but none through the multilevel sectioning method. Nodal micrometastases detected by both multilevel sectioning and immunohistochemistry methods were not associated with larger tumour size, higher depth of invasion, poorer tumour grade, disease recurrence or distant metastasis. We conclude that there is no difference between the two methods in detecting nodal micrometastases. Therefore it is opined that multilevel sectioning is a feasible and yet inexpensive method that may be incorporated into routine practice to detect nodal micrometastases in centres with limited resources.
Fulltext The Role of Breast Cancer Stem Cell-Related Biomarkers as Prognostic Factors

Ko CCH, Chia WK, Selvarajah GT, Cheah YK, Wong YP, Tan GC

Diagnostics (Basel), 2020 Sep 19;10(9).
PMID: 32961774 DOI: 10.3390/diagnostics10090721

Breast cancer is one of the leading causes of cancer-related deaths in women worldwide, and its incidence is on the rise. A small fraction of cancer stem cells was identified within the tumour bulk, which are regarded as cancer-initiating cells, possess self-renewal and propagation potential, and a key driver for tumour heterogeneity and disease progression. Cancer heterogeneity reduces the overall efficacy of chemotherapy and contributes to treatment failure and relapse. The cell-surface and subcellular biomarkers related to breast cancer stem cell (BCSC) phenotypes are increasingly being recognised. These biomarkers are useful for the isolation of BCSCs and can serve as potential therapeutic targets and prognostic tools to monitor treatment responses. Recently, the role of noncoding microRNAs (miRNAs) has extensively been explored as novel biomarker molecules for breast cancer diagnosis and prognosis with high specificity and sensitivity. An in-depth understanding of the biological roles of miRNA in breast carcinogenesis provides insights into the pathways of cancer development and its utility for disease prognostication. This review gives an overview of stem cells, highlights the biomarkers expressed in BCSCs and describes their potential role as prognostic indicators.
Intrauterine Gardnerella vaginalis Infection Results in Fetal Growth Restriction and Alveolar Septal Hypertrophy in a Rabbit Model

Cheah FC, Lai CH, Tan GC, Swaminathan A, Wong KK, Wong YP, et al.

Front Pediatr, 2020;8:593802.
PMID: 33553066 DOI: 10.3389/fped.2020.593802

Background:Gardnerella vaginalis (GV) is most frequently associated with bacterial vaginosis and is the second most common etiology causing intrauterine infection after Ureaplasma urealyticum. Intrauterine GV infection adversely affects pregnancy outcomes, resulting in preterm birth, fetal growth restriction, and neonatal pneumonia. The knowledge of how GV exerts its effects is limited. We developed an in vivo animal model to study its effects on fetal development. Materials and Methods: A survival mini-laparotomy was conducted on New Zealand rabbits on gestational day 21 (28 weeks of human pregnancy). In each dam, fetuses in the right uterine horn received intra-amniotic 0.5 × 102 colony-forming units of GV injections each, while their littermate controls in the left horn received sterile saline injections. A second laparotomy was performed seven days later. Assessment of the fetal pups, histopathology of the placenta and histomorphometric examination of the fetal lung tissues was done. Results: Three dams with a combined total of 12 fetuses were exposed to intra-amniotic GV, and 9 fetuses were unexposed. The weights of fetuses, placenta, and fetal lung were significantly lower in the GV group than the saline-inoculated control group [mean gross weight, GV (19.8 ± 3.8 g) vs. control (27.9 ± 1.7 g), p < 0.001; mean placenta weight, GV (5.5 ± 1.0 g) vs. control (6.5 ± 0.7 g), p = 0.027; mean fetal lung weight, GV (0.59 ± 0.11 g) vs. control (0.91 ± 0.08 g), p = 0.002. There was a two-fold increase in the multinucleated syncytiotrophoblasts in the placenta of the GV group than their littermate controls (82.9 ± 14.9 vs. 41.6 ± 13.4, p < 0.001). The mean alveolar septae of GV fetuses was significantly thicker than the control (14.8 ± 2.8 μm vs. 12.4 ± 3.8 μm, p = 0.007). Correspondingly, the proliferative index in the interalveolar septum was 1.8-fold higher in the GV group than controls (24.9 ± 6.6% vs. 14.2 ± 2.9%, p = 0.011). The number of alveoli and alveolar surface area did not vary between groups. Discussion: Low-dose intra-amniotic GV injection induces fetal growth restriction, increased placental multinucleated syncytiotrophoblasts and fetal lung re-modeling characterized by alveolar septal hypertrophy with cellular proliferative changes. Conclusion: This intra-amniotic model could be utilized in future studies to elucidate the acute and chronic effects of GV intrauterine infections.
Intrathyroidal oxyphilic parathyroid carcinoma: A potential diagnostic caveat in cytology?

Wong YP, Sharifah NA, Tan GC, Gill AJ, Ali SZ

Diagn Cytopathol, 2016 May 26.
PMID: 27229757 DOI: 10.1002/dc.23493

Oxyphilic (oncocytic) parathyroid lesions are very uncommon and their cytological features are rarely described. Due to the similarities in anatomical location and indistinguishable cytomorphological features, these lesions are easily confused with neoplastic and non-neoplastic thyroid lesions on fine needle aspiration (FNA). The diagnosis becomes more challenging in cases of unusual intrathyroidal location of the parathyroid lesions in the absence of clinical evidence of hyperparathyroidism, which simulate thyroid nodules clinically. We describe a case of intrathyroidal oxyphilic parathyroid carcinoma in a 66-year-old female, who presented with a dominant left "thyroid" nodule. FNA smears were cellular, comprising predominantly of oxyphilic cells arranged in papillary-like architecture with occasional nuclear grooves, which was mistaken for oncocytic variant of papillary carcinoma of the thyroid. The histological diagnosis of oxyphilic parathyroid "adenoma" was made following total thyroidectomy. The tumor, unfortunately, recurred 7 years later with associated multiple lung metastases. When dealing with thyroid lesions comprising predominantly of oncocytic cells, one should consider oxyphilic parathyroid neoplasms as one of the differential diagnosis. In difficult equivocal cases, a panel of immunocytochemical stains (PTH, GATA3, TTF-1, PAX8, and thyroglobulin) can be helpful. In addition, a combination of valuable clinical, radiological, and laboratory data, including serum calcium and parathyroid hormone levels are key to arriving at an accurate cytological diagnosis. Diagn. Cytopathol. 2016. © 2016 Wiley Periodicals, Inc.
Fulltext Vascular endothelial growth factor expression in placenta of hypertensive disorder in pregnancy

Azliana AF, Zainul-Rashid MR, Chandramaya SF, Farouk WI, Nurwardah A, Wong YP, et al.

Indian J Pathol Microbiol, 2018 1 13;60(4):515-520.
PMID: 29323064 DOI: 10.4103/IJPM.IJPM_376_16

INTRODUCTION: Hypertensive disorder in pregnancy (HDP) represents the most common medical complication in pregnancy. It is the leading cause of maternal and perinatal mortality and morbidity. Vascular endothelial growth factor (VEGF) stimulates vascular endothelial cell growth, survival, and proliferation, and they are known to be expressed in human placenta. The aim of this study was to determine the VEGF expression in the placenta of hypertensive and normotensive patients.
MATERIALS AND METHODS: This is a retrospective, cross-sectional study from January 1, 2015 to December 31, 2015. A total of 30 placentae comprised of 15 hypertensive and 15 normotensive cases were assessed. VEGF expression in placenta was assessed by immunohistochemistry, and the number of syncytial knots was counted.
RESULTS: Our study showed an increased syncytial knot formation in the placenta of hypertensive mothers. VEGF expression was seen in syncytiotrophoblasts of 14 of the hypertensive cases (14/15, 93.3%), while only two of the normotensive cases were positive (2/15, 13.3%). There were no statistically significant differences in VEGF expression in other placenta cells, that is, cytotrophoblasts (P = 1.0), decidual cells (0.1394), maternal endothelial cells (0.5977), and fetal endothelial cells (P = 1.0).
CONCLUSIONS: This study showed an increased number of syncytial knots is a consistent histological finding in the placenta of patient with HDP. VEGF expression was significantly increased in syncytiotrophoblasts in placenta of hypertensive group, and it could be used as a biomarker for hypertension.
Placental Cyclophilin A Expression in Pregnancies Complicated with Hypertension

Shaaya ES, Yahaya A, Mustangin M, Alfian N, Aizuddin AN, Wong YP, et al.

Int J Environ Res Public Health, 2022 Apr 29;19(9).
PMID: 35564847 DOI: 10.3390/ijerph19095448

Introduction: Cyclophilin A was reported to be increased in the serum of mothers with preeclampsia, and is implicated in its pathogenesis. This study aimed to determine the expression of cyclophilin A in the placenta of mothers with and without hypertension, and to correlate its expression with maternal complications and adverse perinatal outcomes. Materials and Methods: This study consisted of a total of 70 cases (35 cases of mothers with hypertension, and 35 normotensive mothers as a control). Cyclophilin A immunohistochemistry was performed on a paraffin-embedded tissue section of placenta submitted at full thickness in order to evaluate the expression in fetal endothelial cells, cytotrophoblasts, syncytiotrophoblasts, maternal endothelial cells and decidual cells. The cyclophilin A expression was scored as weak, moderate or strong intensity. Results: The hypertensive group was more likely to have preterm deliveries (p < 0.0001), caesarean sections (p < 0.0001), and infants admitted to the intensive care unit (p < 0.001). Fifty-one percent of the fetal endothelial cells and cytotrophoblasts expressed cyclophilin A in the hypertensive group, compared to only 28.6% in the normotensive group. However, the difference was not statistically significant (p = 0.086). Conclusion: We found no significant difference in placental cyclophilin A expression between hypertensive and normotensive mothers. There was also no difference in expression in mothers with and without maternal complications and adverse perinatal outcomes.

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