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Hypertension in the absence of urinary abnormalities - An unusual presentation of anaphylactoid purpura

Thong PL, How KN, Bakrin IH

Med J Malaysia, 2020 07;75(4):436-438.
PMID: 32724011

Henoch-Schonlein Purpura (HSP) or anaphylactoid purpura, currently named IgA vasculitis is the most common form of systemic vasculitis in children. In adults and young infants, HSP tends to have atypical presentations with higher rates of severe gastrointestinal problems and delayed renal complications. While hypertension is a known complication of HSP nephritis, it is rarely seen in individuals with normal renal function and urinary findings. We report a case of a 7-year-old boy with HSP, who presented with abdominal pain and severe hypertension without other features of glomerulonephritis.
Endocrine mucin-producing sweat gland carcinoma - newly described skin appendageal tumours

Bakrin IH, Rajaintharan PS, Tawil Z, Mahayidin H

Malays J Pathol, 2020 Apr;42(1):111-114.
PMID: 32342939

INTRODUCTION: Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a recently described adnexal tumour with a predilection for the face particularly the eye-lids. Considered to be a precursor lesion of mucinous adenocarcinoma, it may represent part of a morphological spectrum. We described a case of this entity, which we believe is the first case to be reported in Malaysia.
CASE REPORT: A 59-year-old Chinese male presented with a slow-growing cystic lesion over the left lower lateral canthal region. The lesion became progressively larger and nodular within the last 6 months. Histologically, the lesion is a well-circumscribed intradermal tumour with pushing borders extending into the subcutaneous tissue. The tumour cells were arranged in lobules of solid, papillary and cribriform architecture. The cells displayed uniform, medium-sized, round to oval nuclei with stippled chromatin pattern and ample eosinophilic granular cytoplasm. Intracellular mucin (as highlighted by mucicarmine stain) was observed in areas with focal extracellular mucin seen. Mitotic figures were not particularly impressive. By immunohistochemistry study, the tumour cells expressed ER, PR, CK7, GCDFP-15, mammaglobin and EMA diffusely. Chromogranin A and synaptophysin highlighted a significant number of tumour cells.
DISCUSSION: The morphology and immunohistochemical profile similarities between EMPSGC and solid papillary carcinoma of the breast (SPCOTB) makes the former considered as the cutaneous analogue of the latter. In fact, one should rule out the possibility of metastatic SPCOTB before considering the diagnosis of EMPSGC.
Cutaneous involvement of multiple myeloma

Mohtarrudin N, Bakrin IH, Ambrose D, Jo Lyn L, Mukhtar NSA

Malays J Pathol, 2021 Apr;43(1):75-79.
PMID: 33903309

Cutaneous multiple myeloma (MM) is a rare disease. It can be primary or secondary in origin. The secondary type is further classified into specific and nonspecific types. The specific type is uncommon and is known as a secondary cutaneous plasmacytoma. We report a case of secondary cutaneous plasmacytoma in a 58-year-old man who had a history of plasma cell tumour of the lung and multiple myeloma. He achieved complete remission after the completion of chemotherapy and autologous stem cell transplant (ASCT). However, five months later, he developed multiple erythematous nodules on the whole body. Skin biopsy revealed diffuse neoplastic cells infiltrate in the reticular dermis with sparing of the upper papillary dermis and epidermis. The neoplastic cells were monotonous and homogenous with variable degrees of cytological atypia. Occasional cells showed distinctive plasma cell features. Plasma cell lineage was confirmed with CD138. The cells were immunoreactive to Kappa. Ki-67 was greater than 90%. They were non-immunoreactive to CD45, CD3, CD20, CD79 alpha and CK AE1/AE3. The findings were consistent with secondary cutaneous plasmacytoma. Our case illustrates that MM may present with nonspecific dermatological manifestations. As specific cutaneous involvement of MM is very uncommon; a high degree of clinical suspicion, detailed medical history and histopathological examination are required to arrive at an early diagnosis.
Transducer-like enhancer of split 1 (TLE1) expression as a diagnostic immunohistochemical marker for synovial sarcoma and its association with morphological features

Bakrin IH, Hussain FA, Tuan Sharif SE

Malays J Pathol, 2016 Aug;38(2):117-22.
PMID: 27568668 MyJurnal

Synovial sarcoma (SS) is a malignant soft tissue tumour of uncertain histogenesis which is defined by the translocation t(X;18) that produces the fusion oncogenes SYT-SSX. The emergence of transducer-like enhancer of split 1 (TLE1) as a new immunohistochemical (IHC) marker for SS has offered an alternative to pathologists in differentiating SS from other histological mimics, especially in the setting of limited molecular facilities. We investigated the utility of IHC TLE1 expression against histomorphological features and other IHC markers in SS and non-SS tumours. Twenty-six cases of histologically diagnosed SS and 7 non-SS (for which SS was in the differential diagnosis) were subjected to TLE1 IHC staining, which was graded from 0 to 3+. Of the 26 SS cases, 12 each were biphasic and monophasic types and 2 were poorly-differentiated. TLE1 was expressed in 22/26 (84.6%) SS cases, of which 11/12 (91.7%) were biphasic, 10/12 (83.3%) monophasic and 1/2 (50%) poorly-differentiated tumours. Two of 7 (28.6%) non-SS cases were positive for TLE1. Immunopositivity of SS and non-SS cases for EMA were 20/26 (76.9%) and 2/7 (28.6%) respectively and for CK7 were 7/26 (26.9%) and 0/7 (0%) respectively. All cases were negative for CD34. Consistent histomorphological features for SS included mild nuclear pleomorphism, alternating tumour cellularity, fascicular growth pattern and thick ropy stromal collagen. In conclusion, TLE1 is not a stand-alone diagnostic IHC marker for SS. However, in the absence of molecular studies, it can contribute added diagnostic value in combination with morphological evaluation and other IHC markers such as EMA and CD34.
Spitz tumour with ALK rearrangement: A case report and literature review

Lai SK, Bakrin IH, Abd Rauf N, Abdul Raub SH

Malays J Pathol, 2024 Apr;46(1):103-108.
PMID: 38682850

Spitz tumour with ALK rearrangement is a recently described entity and a rare tumour. The incidence of Spitz tumour was estimated at 3.63 per 100,000 persons in American paediatric population; while there is no data in Asian population. Here we reported a case of an eleven-year-old Asian boy who presented with a left shin nodule of two months' duration. The skin biopsy revealed a Spitz tumour with predominantly spindle cell morphology arranged in fascicles, vertically orientated nests and radial growth pattern. Junctional component, melanin pigment or Kamino bodies were not identified. Immunohistochemical study displayed homogenous cytoplasmic staining for ALK. Fluorescence in-situ hybridisation (FISH) analysis confirmed ALK rearrangement. Review of the literatures demonstrated that positive ALK immunohistochemistry may not correlate with ALK rearrangement. ALK-rearranged Spitz tumour confirmed with FISH analysis favour clinically benign behaviour despite atypical histomorphology or positive sentinel lymph node. Therefore, correlation of histomorphology, immunohistochemical stain and molecular study are important for the definitive diagnosis of this entity.
Genetic alterations in prostate cancer as diagnostic and prognostic markers

Saeidi H, Ismail P, Samudi Raju C, Khairul-Asri MG, Bakrin IH

Malays J Pathol, 2023 Aug;45(2):149-155.
PMID: 37658525

Prostate cancer is the second-most frequently diagnosed cancer in men worldwide. Serum prostatespecific antigen is currently used for the early detection of prostate cancer. However, new biomarkers are needed to decrease over diagnosis and over treatment of prostate cancer due to limitations of prostate-specific antigen. Recently, molecular biomarkers have shown promising results for diagnosis and prognosis of prostate cancer. Molecular biomarkers have improved the sensitivity and specificity of prostate-specific antigen and studies are ongoing to identify molecular biomarkers as a replacement for prostate-specific antigen. This review aims to give an overview of emerging molecular biomarkers for diagnosis and prognosis of prostate cancer.
Homologous recombination repair gene mutations in Malaysian prostate cancer patients

Saeidi H, Raju CS, Ismail P, Raub SHA, Omar N, Hisyam Bakrin I

Cell Mol Biol (Noisy-le-grand), 2022 Aug 31;68(8):22-26.
PMID: 36800845 DOI: 10.14715/cmb/2022.68.8.4

Genetic alterations in the homologous recombination repair (HRR) genes are associated with an increased risk of prostate cancer development, and patients harboring these mutations can benefit from targeted therapy. The main aim of this study is to identify genetic alterations in HRR genes as a potential target for targeted treatment. In this study, targeted next generation sequencing (NGS) is used to analyze mutations in the protein-coding regions of the 27 genes involved in HRR and mutations in hotspots of 5 cancer-associated genes in four FFPE samples and three blood samples from prostate cancer patients. We identified two mutations in TP53 and KRAS. We also identified four conflicting interpretations of pathogenicity variants in BRCA2, STK11 genes and one variant of uncertain significance in the RAD51B gene. In addition, we detected one drug response variant in TP53, and two novel variants in CDK12 and ATM. Our results revealed some actionable pathogenic and potential pathogenic variants that may be associated with response to the Poly (ADP-ribose) polymerase (PARP) inhibitor treatment. More studies in a larger cohort are needed to evaluate and determine the association of HRR mutations with prostate cancer.
Impact of the COVID-19 pandemic on cytology practice: An international survey in the Asia-Pacific region

Wang YH, Bychkov A, Chakrabarti I, Jain D, Liu Z, He S, et al.

Cancer Cytopathol, 2020 Dec;128(12):895-904.
PMID: 32931161 DOI: 10.1002/cncy.22354

BACKGROUND: The purpose of the current study was to examine the impact of coronavirus disease 2019 (COVID-19) on various aspects of cytology practice in the Asia-Pacific region.
METHODS: An online questionnaire was distributed to cytopathology laboratories in 24 Asia-Pacific countries to explore the impact of restrictive measures on access to health care, use of general and personal protective equipment (PPE), and changes in cytology workflow and workload from February to April 2020.
RESULTS: A total of 167 cytopathology laboratories from 24 countries responded to the survey; the majority reported that restrictive measures that limited the accessibility of health care services had been implemented in their cities and/or countries (80.8%) and their hospitals (83.8%). The respondents noted that COVID-19 had an impact on the cytologic workflow as well as the workload. Approximately one-half of the participants reported the implementation of new biosafety protocols (54.5%) as well as improvements in laboratory facilities (47.3%). Rearrangement or redeployment of the workforce was reported in 53.3% and 34.1% of laboratories, respectively. The majority of the respondents reported a significant reduction (>10%) in caseload associated with both gynecological (82.0%) and nongynecological specimens (78.4%). Most laboratories reported no significant change in the malignancy rates of both gynecological (67.7%) and nongynecological specimens (58.7%) compared with the same period in 2019.
CONCLUSIONS: The results of the survey demonstrated that the COVID-19 pandemic resulted in a significant reduction in the number of cytology specimens examined along with the need to implement new biosafety protocols. These findings underscore the need for the worldwide standardization of biosafety protocols and cytology practice.
Epidemiology and clinical profiles of cutaneous graft versus host disease in allogeneic peripheral blood stem cell transplantation

Kamal Rodin NS, Ismail NA, Abdul Wahid SF, Jamil A, Syed Zakaria SZ, Syed Abd Kadir SS, et al.

Malays J Pathol, 2021 Dec;43(3):361-373.
PMID: 34958057

INTRODUCTION: The epidemiology of cutaneous graft versus host disease (GVHD) in allogeneic peripheral blood stem cell transplantation (PBSCT) in Malaysia has not been described.
MATERIALS AND METHODS: We retrospectively analysed 691 allogeneic PBSCT patients between 2010-2017 in two centers.
RESULTS: The prevalence of cutaneous GVHD was 31.4% (217/691). No associations were detected with race, age or gender of donor and recipients. Cutaneous GVHD was associated with host cytomegalovirus (CMV) seropositivity (p<0.01), conditioning (p<0.01), GVHD prophylaxis (p=0.046) and survival (p<0.01). Majority developed the acute form (58.1%;126/217). Biopsies in 20.7% (45/217) showed 55.6% positivity for GVHD. Overall, involvement was non-severe. A majority demonstrated complete response (CR) to first-line corticosteroids (70.0%;152/217). Secondline therapies (extracorporeal phototherapy (ECP), psolaren ultraviolet A (PUVA), mycophenolate, tumour necrosis factor (TNF) inhibitors, interleukins inhibitors, or CD20 monoclonal antibodies) were required in 65/217, with 38.5% CR. Second-line therapy was associated with gender (p=0.042), extra-cutaneous GVHD (p=0.021), treatment outcomes (p=0.026) and survival (p=0.048). Mortality in cutaneous GVHD was 24.0% with severe sepsis being the leading cause at Day 100 (7.8%) and 5-years (7.8%), and relapsed disease at 2-years (32.7%). In steroid refractoriness, severe GVHD caused 30.8% mortality. In cutaneous GVHD, survival at Day 100 was 95.4%; 80.2% at 2-years and 73.1% at 5-years. The median survival in cutaneous GVHD was significantly shorter at 55 months, compared to those without GVHD at 69 months (p=0.001).
CONCLUSION: Cutaneous involvement is the commonest clinical manifestation of GVHD. A larger national study is warranted to further analyse severity and outcome of multiorgan GVHD, and factors associated with steroid refractoriness.