Breast Tumor Angiogenesis and Tumor-Associated Macrophages: Histopathologist's Perspective

Much progress has been made since the conceptualization of tumor angiogenesis—the induction of growth of new blood vessels by tumor—as a salient feature of clinically significant primary or metastatic cancers. From a practicing histopathologist's point of view, we appraise the application of this concept in breast cancer with particular reference to the evaluation of proangiogenic factors and the assessment of new microvessels in histopathological examination. Recently, much focus has also been centered on the active roles played by tumor-associated macrophages in relation to tumor angiogenesis. We review the literature; many data supporting this facet of tumor angiogenesis were derived from the breast cancer models. We scrutinize the large body of clinical evidence exploring the link between the tumor-associated macrophages and breast tumor angiogenesis and discuss particularly the methodology and limitations of incorporating such an assessment in histopathological examination

Transducer-like enhancer of split 1 (TLE1) expression as a diagnostic immunohistochemical marker for synovial sarcoma and its association with morphological features

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

Barrett's Esophagus in an Area with an Exceptionally Low Prevalence of Helicobacter pylori Infection

Objective. This study was undertaken to gain an insight into the relationship between Helicobacter pylori (H. pylori) infection, Barrett's esophagus and reflux esophagitis in an area of exceptionally low prevalence of H. pylori infection. Methods. A total of 1895 consecutive upper endoscopies performed between January 2005 and July 2007 were reviewed. 120 cases of columnar-lined esophagus and endoscopic esophagitis were evaluated. H. pylori infection was determined using the urease test and/or histology. Results. The rate of endoscopic esophagitis was 5.49% (80 Malays, 24 non-Malays) while histological reflux esophagitis was found in 3.75% (56 Malays, 15 non-Malays). Barrett's esophagus was present in 0.79% (11 Malays, 4 non-Malays). H. pylori infection was present in 8/120 or 6.67% subjects. Conclusion. The low rate of Barrett's esophagus in this population does not support the hypothesis that the absence of H. pylori infection is more than a minor risk factor for Barrett's esophagus

Chronic Trichuris trichiura Infection Presenting as Ileocecal Valve Swelling Mimicking Malignancy

A 46-year-old man presented with a history of passing bright red blood per rectum over the last one month. He also had on and off diarrhea with visible mucus in the stool for two months' duration. Further history was unremarkable, and physical examination revealed hemorrhoids which were subsequently banded. A colonoscopy was arranged in view of the prolonged diarrhea whereby an edematous and swollen ileocecal valve was seen. This was shown to be due to Trichuris trichiura infection, confirmed on histopathological examination of biopsies taken from the site. The patient was started on oral albendazole treatment and has been asymptomatic on latest followup. This case illustrates an accidental finding of T. trichuria infection on colonoscopic examination, which was done to investigate the patient's prolonged diarrhea

Bilateral tonsillar lymphangiomatous polyps in a snoring child

Lymphangiomatous polyps of the palatine tonsil are a rare clinical entity with only about 30 odd cases ever reported. All the cases in the literature were described as unilateral tonsillar diseases, except for one paediatric case which had bilateral tonsillar involvement. Due to its unilateral presentation and suspicious appearance similar to tonsillar malignancy, lymphangiomatous polyps may cause heightened anxiety to both patients and doctors alike on a routine oropharyngeal examination. Owing to its rarity and a variety of complex nomenclatures, this condition may also be confusing to the treating otolaryngologist as well as junior pathologist. We report an extremely rare case of bilateral tonsillar lymphangiomatous polyps in a snoring child that was successfully treated surgically via tonsillectomy

Sporadic malignant peripheral nerve sheath tumour in a 3-year-old girl: A diagnostic challenge

Introduction: Malignant peripheral nerve sheath tumour (MPNST) is an uncommon malignant neoplasm of childhood with unfavourable prognosis. Only 1.7% of the cases have been reported in children less than five years of age and approximately one-half arise from a benign peripheral nerve sheath tumour especially in background of neurofibromatosis type 1 (NF1). Primary MPNST in children are even rarer. Case Report: A 3-year-old Malay girl presented with painful right axillary swelling for 6 months duration, initially treated as axillary lymphadenitis and she defaulted follow up. She came back 4 months later with enlargement of the swelling. The biopsy was reported as Schwannoma which correlates with MRI findings of benign peripheral nerve sheath tumour. Final diagnosis after debulking surgery was consistent with MPNST. She succumbed to death 20 months after her initial diagnosis of advanced MPNST and lung metastasis. Pathological findings: Grossly, a huge partlycircumscribed soft tissue mass noted arising from a nerve with solid greyish yellowish myxoid cut surface. Spindle shaped cells arranged in herringbone pattern with marked pleomorphism, brisk mitosis and extensive necrosis are seen microscopically. Immunohistochemistry shows patchy S100 protein staining with loss of expression of H3K27 trimethylation. Conclusion: Although MPNST is rare in paediatric age group, diagnosis should be considered in children without NF1 with rapidly evolving and painful mass in the distribution of a peripheral nerve. In this case, the diagnosis was delayed and made after surgery. Due to its morphologic heterogeneity and lack of specific immunohistochemical markers, MPNST remains a diagnostic challenge

Sporadic malignant peripheral nerve sheath tumour in a 3-year-old girl: A diagnostic challenge

Introduction: Malignant peripheral nerve sheath tumour (MPNST) is an uncommon malignant neoplasm of childhood with unfavourable prognosis. Only 1.7% of the cases have been reported in children less than five years of age and approximately one-half arise from a benign peripheral nerve sheath tumour especially in background of neurofibromatosis type 1 (NF1). Primary MPNST in children are even rarer. Case Report: A 3-year-old Malay girl presented with painful right axillary swelling for 6 months duration, initially treated as axillary lymphadenitis and she defaulted follow up. She came back 4 months later with enlargement of the swelling. The biopsy was reported as Schwannoma which correlates with MRI findings of benign peripheral nerve sheath tumour. Final diagnosis after debulking surgery was consistent with MPNST. She succumbed to death 20 months after her initial diagnosis of advanced MPNST and lung metastasis. Pathological findings: Grossly, a huge partlycircumscribed soft tissue mass noted arising from a nerve with solid greyish yellowish myxoid cut surface. Spindle shaped cells arranged in herringbone pattern with marked pleomorphism, brisk mitosis and extensive necrosis are seen microscopically. Immunohistochemistry shows patchy S100 protein staining with loss of expression of H3K27 trimethylation. Conclusion: Although MPNST is rare in paediatric age group, diagnosis should be considered in children without NF1 with rapidly evolving and painful mass in the distribution of a peripheral nerve. In this case, the diagnosis was delayed and made after surgery. Due to its morphologic heterogeneity and lack of specific immunohistochemical markers, MPNST remains a diagnostic challenge

Prospective diagnostic study on the use of narrow‐band imaging on suspicious lesions during colonoscopy examination

Introduction: Colonoscopy is the gold standard to detect colorectal neoplasm. Narrow-band imaging (NBI) has a good diagnostic accuracy to differentiate between neoplastic and non-neoplastic colorectal lesions. This study explores the diagnostic validity of NBI colonoscopy as well as its associated factors related to neoplastic and non-neoplastic colorectal lesions. Methods: This study enrolled 100 patients in a single-center tertiary teaching hospital. Patients presented for screening colonoscopy, and those with suspicious colorectal lesions were included in this study. During colonoscopy, the most suspicious lesion in each patient was analyzed using the NBI system based on Sano’s classification. Each lesion was biopsied for histopathological analysis, the gold standard. Endoscopic images were captured electronically. The sensitivity, specificity, and diagnostic accuracy of NBI colonoscopy were assessed. Other associated factors related to neoplastic and non-neoplastic lesions were analyzed accordingly. Results: The sensitivity and specificity of the NBI were 88.2% and 71.9%, respectively. The area under the receiver–operator curve was 0.801, indicating that NBI has a good ability to differentiate between disease and non-disease. There are significant associations between histopathological examination outcomes and both presenting symptoms, especially weight loss, and lesion site, even after other variables were controlled (P < 0.05). Conclusion: The NBI system in colonoscopy was capable of distinguishing neoplastic from non-neoplastic colorectal lesions. It indicates an acceptable level of agreement with histopathology, the gold standard. However, the role of NBI in screening and surveillance in Malaysia still needs further evaluation and exploration

The value of H3K27me3 immunohistochemistry in differentiating malignant peripheral nerve sheath tumour with its histologic mimickers

Background: Diagnosis of malignant peripheral nerve sheath tumor (MPNST) is rather challenging due to its divergent morphologic heterogeneity and lack of specific ancillary test. The emergence of H3K27 trimethylation (H3K27me3) as a new immunohistochemistry (IHC) marker for MPNST have recently available to assist pathologists in differentiating MPNST from other histologic mimics. We aim to study the expression pattern of H3K27me3 in MPNST and its histologic mimickers and their association with the clinicopathological data. Methodology: A total of 59 benign and malignant spindle cell tumours (18 MPNST and 41 of its histologic mimickers which included 10 schwannoma, 13 neurofibroma, 4 synovial sarcoma, 3 fibrosarcoma, 2 gastrointestinal stromal tumour (GIST), 4 leiomyosarcoma, 1 spindle cell liposarcoma, 1 solitary fibrous tumour, 2 low grade fibromyxoid sarcoma and 1 unclassified spindle cell sarcoma), diagnosed from January 1998 to April 2018 in Hospital Universiti Sains Malaysia (HUSM) were tested for H3K27me3 by IHC. The MPNST histological grade was assessed based on the French Fe’de’ ration Nationale des Centres de LutteContre le Cancer (FNCLCC) for 3 tiers system (low grade, intermediate grade and high grade). The clinicopathological data were retrieved from the patients’ record. Results: A total of 61.1% (11/18 MPNST) showed loss of H3K27me3 expression which is statistically significant as compared to its histologic mimics (p<0.001). Similar findings (p=0.026) were also observed in high grade MPNST (81.8%), intermediate grade MPNST (100%) and 0% in low grade MPNST. Conclusion: H3K27me3, combined with other panel of markers, is useful in MPNST diagnosis to differentiate it from the histological mimickers