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Oesophageal hepatoid carcinoma with liver metastasis, a diagnostic dilemma

Yahaya A, Wa Kammal WS, Abd Shukor N, Osman SS

Malays J Pathol, 2019 Apr;41(1):59-63.
PMID: 31025640

Alpha-fetoprotein (AFP)-producing carcinoma which microscopically mimics hepatocellular carcinoma (HCC) is a rare entity known as hepatoid adenocarcinoma (HC). They usually arise in the stomach, while oesophageal origin is only occasionally encountered. This tumour is highly aggressive and is associated with a poor prognosis. They frequently metastasise to the liver, thus giving rise to diagnostic difficulty, especially in cases where simultaneous oesophageal and liver mass are present. We reported a case of oesophageal hepatoid carcinoma with multiple liver metastasis, that was associated with an increased serum AFP. The distinction between HCC and HC is important because HC is more aggressive and has a poorer prognosis with limited therapeutic options. An extensive diagnostic work-up which include a thorough clinical history, radiological investigations (computed tomography or magnetic resonance imaging) as well as tissue biopsy supported by a panel of immunohistochemical markers are necessary to aid in the diagnosis of HC.
Diffuse large B-cell lymphoma of the small intestine in a patient with refractory coeliac disease

Ahmad Affandi K, Abd Shukor N, Mohamed Rose I, Raja Ali RA, Masir N

Malays J Pathol, 2019 Apr;41(1):65-69.
PMID: 31025641

INTRODUCTION: Coeliac disease enteropathy is associated with an increased risk of lymphomas. Enteropathy-associated T-cell lymphoma is the principal malignancy related to coeliac disease. However, studies have shown that other types of lymphoma such as diffuse large B-cell lymphoma may also be associated with coeliac disease.
CASE REPORT: We report a 54-year-old Caucasian man who presented with chronic diarrhoea and weight loss. He was diagnosed with coeliac disease based on positive serology results and duodenal, jejunal, and ileal biopsies that showed villous atrophy. Despite adherence to a gluten-free diet, there was no clinical remission and enteropathy-associated T cell lymphoma was suspected. Repeated endoscopic biopsy showed persistent mucosal disease but no evidence of lymphoma. Several weeks later he presented with a perforated jejunum. Histology of the resected jejunum showed diffuse infiltration of submucosa and muscularis propria by malignant lymphoid cells sparing the mucosa. The cells expressed CD20, CD79α, CD10 and BCL6 and ki67 of 80%, consistent with diffuse large B-cell lymphoma.
DISCUSSION: It is suspected that the undetected lymphoma may have contributed to the persistent malabsorption syndrome rendering the patient unresponsive to treatment. Despite thorough clinical and endoscopic evaluation and multiple biopsies, histologic diagnosis of DLBCL was only confirmed following resection of the perforated jejunum.
Stromal expression of CD10 in invasive breast carcinoma and its association with tumour stage, grade, ER, PR and HER2 status

Kamarudin NA, Abd Shukor N, Farouk WI, Muhammad Hanapi NA, Mohammed F

Malays J Pathol, 2021 Dec;43(3):389-396.
PMID: 34958060

INTRODUCTION: Tumour microenvironment (TME) has been postulated to be involved in cancer development and disease progression. Studies have shown CD10 expressed in cancer-associated fibroblasts (CAF) within TME is associated with aggressive biological behaviour and poor prognosis. The aim of this study was to evaluate stromal CD10 expression in invasive breast cancer and its correlation with tumour stage, grade, Estrogen receptor (ER), Progesterone receptor (PR) and HER2 status.
MATERIALS AND METHODS: A total of 226 invasive breast carcinoma cases were selected and assembled into tissue microarrays (TMAs). The stromal expression of CD10 was immunohistochemically analysed.
RESULTS: Stromal CD10 was positive in 67 (29.6%) cases of invasive breast carcinoma. The frequency of positive stromal staining was significantly higher in the cases with ER-negative (P=0.000). CD10 stromal negativity was significantly higher in luminaltype cases (P=0.001). However, there was no correlation between stromal CD10 expression with tumour grade, stage, PR and HER2 status.
CONCLUSION: Positive CD10 stromal expression correlates with ER-negative invasive breast carcinomas, while negative CD10 stromal expression correlates with luminal type invasive breast carcinomas. This demonstrates that stromal CD10 expression within the TME constitutes a potential prognostic marker and therapeutic target. Future studies are necessary to evaluate other stromal markers within the TME immunohistochemically as well as its molecular basis in order to confirm the definite role of stromal CD10.
Histopathological diagnoses in soft tissue tumours: an experience from a tertiary centre in Malaysia

Jalaludin ND, Mohd Dusa N, Hassan MR, Abd Shukor N

Malays J Pathol, 2017 Dec;39(3):209-216.
PMID: 29279582 MyJurnal

Soft tissue tumours are a group of remarkably diverse neoplasms that frequently pose significant diagnostic challenges to general pathologists. This study aimed to compare the agreement of histopathological diagnoses between general pathologists from various referral institutes and the referred soft tissue pathologist in a tertiary centre. The common discrepancies and their causes are also presented here. A retrospective study was conducted on 243 cases of potential soft tissue tumours referred to Hospital Kuala Lumpur, Malaysia over a period of 5 years. Reports by the referring pathologists and the soft tissue pathologist were compared based on tumour classification and tumour behaviour. Overall, there was moderate agreement in soft tissue tumour diagnoses in both tumour classification (weighted κ = 0.423) and tumour behavior (weighted κ = 0.548). The highest agreement of tumour classification was seen in the adipocytic tumours (21/28 cases), Ewing sarcoma (5/7 cases) and smooth-muscle tumours (3/5 cases). The highest rates of discrepancies were the so-called fibrohistiocytic tumours (7/11 cases), vascular tumours (9/15 cases) and undifferentiated/ unclassified sarcomas (19/32 cases). Full agreement for tumour behaviour was seen in 178 cases and there were 21 cases of zero agreement. Liposarcoma, alveolar soft part sarcoma and benign fibrous histiocytoma were the most frequent benign/malignant diagnostic discrepancies. The most common causes of discrepancy were wrong morphological interpretation followed by insufficient immunohistochemical stains performed. In conclusion, review of diagnosis by a pathologist specialized in soft tissue improves the quality of diagnosis in these heterogenous and rare tumours. A good panel of immunohistochemical stains with additional molecular study is crucial in the general hospital laboratories practice.
CD47 and CD36 expressions in the placenta of mothers with chorioamnionitis

Hanim BS, Rahim RA, Mohd Salleh MF, Zakaria H, Abd Shukor N

Malays J Pathol, 2023 Dec;45(3):463-471.
PMID: 38155387

INTRODUCTION: Chorioamnionitis is the inflammation of the placenta and is histologically defined as the presence of neutrophilic infiltration into the chorio-amnion membrane with and without involvement of the umbilical cord. Currently, the inflammatory mediators involved in the eliciting of inflammatory response is still largely under investigation. CD47 and CD36 are pro-inflammatory molecules that are still under investigation. The aim of this study was to determine the expressions of CD47 and CD36 in the placenta of mothers with chorioamnionitis.
MATERIALS AND METHODS: This was a cross-sectional study, involving a total of 100 cases that comprised of acute subchorionitis (stage I, n=20), acute chorioamnionitis (stage II, n=20), acute necrotising chorioamnionitis (stage III, n=20) and non-chorioamnionitis placenta as control (n=40). All tissue blocks were retrieved from the archived pathology record over a period of 4 years. CD36 and CD47 immunohistochemistry were performed on all cases and their expression in various cell types on the placenta were analysed.
RESULTS: CD36 was expressed only on the foetal vascular endothelial cells. Interestingly, CD47 showed positive staining on the neutrophils and its expression was significantly different between maternal inflammatory response stage II chorioamnionitis (n=13/20, p<0.001) with stage I and stage III chorioamnionitis.
DISCUSSION: Our study showed CD47 was expressed in the neutrophils and it was associated with poorer perinatal outcomes and it may have a role in the pathogenesis of chorioamnionitis.
Fulltext The 'CASTLE' tumour: An extremely rare presentation of a thyroid malignancy. A case report

Dualim DM, Loo GH, Suhaimi SNA, Md Latar NH, Muhammad R, Abd Shukor N

Ann Med Surg (Lond), 2019 Aug;44:57-61.
PMID: 31312445 DOI: 10.1016/j.amsu.2019.06.013

Thyroid carcinoma showing thymic-like differentiation (CASTLE) is a rare malignancy of the thyroid gland, and it accounts for 0.1-0.15% of all thyroid cancers. As the name suggests, it has a histological and immunophenotypic resemblance to thymic carcinoma. Preoperative diagnosis of CASTLE can be difficult as its clinical manifestations, and histological characteristic resembles other aggressive and advanced thyroid carcinomas. It is essential to distinguish CASTLE from other aggressive neoplasms as the former has a more favourable prognosis. Immunohistochemical staining with CD5 can help to differentiate thyroid CASTLE from other aggressive thyroid neoplasms. Due to the rarity of this disease, there is no clear definitive treatment strategy. Surgical resection of CASTLE is usually attempted initially. Nodal involvement and extrathyroidal extension are shown to be the main prognostic factors that influenced the survival of patients. Therefore, complete resection of the tumour is vital to reduce local recurrence rates and to improve the chance of long-term survival. Radiotherapy (RT) for CASTLE is an effective treatment. Curative surgery followed by adjuvant RT should be considered in cases with extrathyroidal extension and nodal metastases. With RT, shrinkage of the tumour and reduction of local recurrence rate is possible. With that in mind, we present a case of CASTLE who presented with airway compression symptoms three years after thyroid surgery. He subsequently underwent tumour debulking surgery and a tracheostomy. The patient refused adjuvant chemoradiotherapy, and during our serial follow-up, he is well and symptom-free.
Parotid gland oncocytic carcinoma: A rare entity in head and neck region

Wan Ahmad Kammal WS, Azman M, Salleh AA, Md Pauzi SH, Abd Shukor N

Malays J Pathol, 2020 Aug;42(2):283-286.
PMID: 32860383

Oncocytic carcinoma of the salivary gland is an uncommon tumour in the head and neck region. Owing to its rarity, identifying the histopathological features of a malignant tumour can be difficult and challenging. We report a case of a 70-year-old man who presented with a left facial weakness for six months in a background history of left parotid swelling over the past 10 years. Clinical examination revealed a 3x3cm left parotid mass and grade 4 facial nerve palsy. Fine needle aspiration of the mass showed scattered cohesive, monolayered sheets of uniform oncocytic cells. Subsequently, a left total parotidectomy and selective neck dissection were performed. Histological examination showed sheets of small oncocytes with minimal nuclear atypia. Evidence of nerve entrapment, capsular invasion and perivascular permeation were identified in focal areas. Thus, a final diagnosis of oncocytic carcinoma was rendered.
A Case Report of a Rare ER+, PR- Pure Metaplastic Breast Squamous Cell Carcinoma with HER2 Overexpression

Adam SA, Kamaruddin KN, Abd Shukor N, Abdullah Suhaimi SN, Ismail F, Md Yasin M

Am J Case Rep, 2023 Dec 04;24:e941448.
PMID: 38048289 DOI: 10.12659/AJCR.941448

BACKGROUND Breast squamous cell carcinoma (SCC) is a subtype of metaplastic breast carcinoma (MBC), which is a rare malignancy and accounts for 0.1% of all invasive breast carcinomas. Guidelines on definitive management and treatment of breast SCC are not well established, given its rarity and diverse immunohistochemistry (IHC) profile, and lack of clinical data. Most cases of breast SCC are triple-negative breast cancer - negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). This case report outlines the clinicopathological profile of a pure breast SCC case with a rare IHC profile; HER2 and ER positive. CASE REPORT A 41-year-old woman presented with a right breast mass that had been growing for 2 months. Biopsy confirmed breast SCC, a rare malignancy with IHC profile as follows: HER2 overexpression, ER positive, and PR negative. She underwent neoadjuvant chemotherapy for 3 months followed by right mastectomy with axillary clearance, adjuvant radiotherapy, and oral tamoxifen therapy. Unfortunately, she did not receive anti-HER2 therapy. She developed early locoregional recurrence at 2 months postoperatively, which was treated with excision of the right chest wall and transverse rectus abdominis musculocutaneous (TRAM) flap. She developed liver and lung metastasis and succumbed to her disease at 15 months post-diagnosis. CONCLUSIONS Breast SCC is a rare and aggressive tumor with heterogeneous clinicopathological features. Available guidelines do not outline the definitive treatment for breast SCC, given its rarity and heterogenous IHC profile, leading to a general lack of clinical data. Hence, due to the challenges in managing this rare condition, treatment modalities need to be individualized.
Fulltext Long term outcome of immunoglobulin A (IgA) nephropathy: A single center experience

Mohd R, Mohammad Kazmin NE, Abdul Cader R, Abd Shukor N, Wong YP, Shah SA, et al.

PLoS One, 2021;16(4):e0249592.
PMID: 33831052 DOI: 10.1371/journal.pone.0249592

INTRODUCTION: IgA nephropathy (IgAN) has a heterogeneous presentation and the progression to end stage renal disease (ESRD) is often influenced by demographics, ethnicity, as well as choice of treatment regimen. In this study, we investigated the long term survival of IgAN patients in our center and the factors affecting it.
METHODS: This study included all biopsy-proven IgAN patients with ≥ 1year follow-up. Patients with diabetes mellitus at diagnosis and secondary IgAN were excluded. Medical records were reviewed for demographics, clinical presentation, blood pressure, 24-hour urine protein, serum creatinine, renal biopsy and treatment received. The primary outcome was defined as combined event of 50% estimated glomerular filtration rate (eGFR) reduction or ESRD.
RESULTS: We included 130 (74 females; 56 males) patients of mean age 38.0 ± 14.0 years and median eGFR of 75.2 (interquartile range (IQR) 49.3-101.4) ml/min/1.73m2. Eighty-four (64.6%) were hypertensive at presentation, 35 (26.9%) had nephrotic syndrome and 57 (43.8%) had nephrotic range proteinuria (NRP). Median follow-up duration was 7.5 (IQR 4.0-13.0) years. It was noted that 18 (13.8%) developed ESRD and 34 (26.2%) reached the primary outcome. Annual eGFR decline was -2.1 (IQR -5.3 to -0.1) ml/min/1.73m2/year, with median survival of 20 years. Survival rates from the combined event (50% decrease in eGFR or ESRD) at 10, 20 and 30 years were 80%, 53% and 25%, while survival from ESRD were 87%, 73% and 65%, respectively. In the univariate analysis, time-average proteinuria (hazard ratio (HR) = 2.41, 95% CI 1.77-3.30), eGFR <45ml/min/1.73m2 at biopsy (HR = 2.35, 95% CI 1.03-5.32), hypertension (HR = 2.81, 95% CI 1.16-6.80), mean arterial pressure (HR = 1.02, 95% CI 1.01-1.04), tubular atrophy/interstitial fibrosis score (HR = 3.77, 95% CI 1.84-7.73), and cellular/fibrocellular crescent score (HR = 2.44, 95% CI 1.19-5.00) were found to be significant. Whereas only time-average proteinuria (TA-proteinuria) remained as a significant predictor in the multivariate analysis (HR = 2.23, 95% CI 1.57-3.16).
CONCLUSION: In our cohort, TA-proteinuria was the most important predictor in the progression of IgAN, irrespective of degree of proteinuria at presentation.