Kein-Seong Mun

Loss of PTEN expression is associated with IGFBP2 expression, younger age, and late stage in triple-negative breast cancer

OBJECTIVES To investigate the association between PTEN loss and IGFBP2 expression in a series of triple-negative breast cancers and to relate this expression to basal cytokeratin expression and clinicopathologic features. METHODS One hundred and one formalin-fixed and paraffin-processed triple-negative breast cancer cases from the University of Malaya Medical Centre were tested immunohistochemically for cytokeratins 5/6 and 14, PTEN, and IGFBP2. The resulting slides were scored for proportion and intensity of staining. RESULTS Loss of tumor nuclear and cytoplasmic staining for PTEN occurred in 48.3% of cases and was significantly associated with younger age at diagnosis (47 years compared with 57 years in those without PTEN loss; P = .005). Independent predictors of PTEN loss were late stage at presentation (P = .026), cytokeratin 5/6 positivity (P = .028), and IGFBP2 expression (P = .042). High levels of IGFBP2 expression were seen in 32% of cases; an independent predictor of high levels was cytokeratin 14 negativity (P = .005). PTEN loss and high levels of IGFBP2 expression were associated with poorer survival, but neither of these trends was significant. CONCLUSIONS PTEN loss is a frequent event in triple-negative breast cancers and is significantly associated with younger age at onset of breast cancer, late stage, and IGFBP2 expression.

The Estrogen Receptor Negative-Progesterone Receptor Positive Breast Carcinoma is a Biological Entity and not a Technical Artifact

The ER-/PR+ breast tumor may be the result of a false ER negative result. The aim of this study was to investigate whether there is a difference in patient and tumor characteristics of the ER-/PR+ phenotype in an Asian setting. A total of 2629 breast cancer patients were categorized on the basis of their age, ethnicity, tumor hormonal receptor phenotype, grade and histological type. There were 1230 (46.8%) ER+/PR+, 306 (11.6%) ER+/PR-, 122 (4.6%) ER-/PR+ and 972 (37%) ER-/PR-. ER-/PR+ tumors were 2.5 times more likely to be younger than 50 years at diagnosis (OR: 2.52; 95% CI: 1.72-3.67). Compared to ER+/PR+ tumors, the ER-/ PR+ phenotype was twice more likely to be associated with grade 3 tumors (OR:2.02; 95%CI: 1.00-4.10). In contrast, compared to ER-/PR- tumors, the ER-/PR+ phenotype was 90% less likely to be associated with a grade 3 tumor (OR: 0.12; 95%CI:0.05-0.26), and more likely to have invasive lobular than invasive ductal histology (OR: 3.66; 95%CI: 1.47-9.11). These results show that the ER-/PR+ phenotype occurs in a younger age group and is associated with intermediate histopathological characteristics compared to ER+/PR+ and ER-/PR- tumors. This may imply that it is a distinct entity and not a technical artifact.

Factors affecting estrogen receptor status in a multiracial Asian country: An analysis of 3557 cases

Estrogen receptor (ER) positive rates in breast cancer may be influenced by grade, stage, age and race. This study reviews the ER positive rates over a 15-year period at the University Malaya Medical Centre, Kuala Lumpur, Malaysia. Data on ER status of 3557 patients from 1994 to 2008 was analyzed. ER status was determined by immunohistochemistry with a cut-off point of 10%. ER positivity increased by about 2% for every 5-year cohort, from 54.5% in 1994-1998 to 58.4% in 2004-2008. Ethnicity and grade were significantly associated with ER positivity rates: Malay women were found to have a higher risk of ER negative tumors compared with Chinese women. Grade 1 cancers were nine times more likely to be ER positive compared with grade 3 cancers. In summary, the proportion of ER positive cancers increased with each time period, and ethnicity and grade were independent factors that influenced ER positive rates.

p16(INK4a) is a useful marker of human papillomavirus integration allowing risk stratification for cervical malignancies.

The present study was conducted to assess utility of p16(INK4a) immunopositivity as a surrogate marker for genomic integration of high-risk human papillomavirus infection (hrHPV). A total of 29 formalin-fixed, paraffin-embedded cervical low-grade squamous intraepithelial lesions (LSILs), 27 high-grade squamous intraepithelial lesions (HSILs) and 53 invasive squamous cell carcinomas (SCCs), histologically-diagnosed between 1st January 2006 to 31st December 2008 at the University of Malaya Medical Centre were stained for p16(INK4a) (CINtec Histology Kit (REF 9511, mtm laboratories AG, Heidelberg, Germany). Immunopositvity was defined as diffuse staining of the squamous cell cytoplasm and or nucleus (involving > 75% of the intraepithelial lesions or SCCs). Staining of basal and parabasal layers of intraepithelial lesions was pre-requisite. One (3.4%) LSIL, 24 (88.9%) HSIL and 46 (86.8%) SCC were p16(INK4a) immunopositive. All normal squamous epithelium did not express p16(INK4). p16(INK4a) expression was significantly lower (p<0.05) in LSIL compared with HSIL and SCC with no difference in expression between HSIL and SCC.The increased p16(INK4a) immunopositivity in HSIL and SCC appears in line with the integrated existence of the hrHPV and may provide more insightful information on risk of malignant transformation of cervical squamous intraepithelial lesions than mere hrHPV detection.

Plexiform angiomyxoid myofibroblastic tumour of the stomach

Sir, We report a single case of plexiform angiomyxoid myofibroblastic (PAM) tumour of stomach, a rare entity. This is only the third case reported in the literature. This condition was first described by Takahashi et al. in 2007. A 23-year-old female presented in early August 2008 with a five day history of passing dark coloured stool. There was no history of abdominal pain. Investigations showed normal peripheral blood film, but a low haemoglobin level of 9.4 gm/dL. Her chest X-ray was normal. Computed tomography (CT) scan of the abdomen showed a large mass in the gastric antrum measuring about 4.86 7.2 cm. Gastroscopy revealed a tumour mainly in the wall of the stomach with focal ulceration of the mucosa. She underwent partial gastrectomy. Post-operative recovery was uneventful. She remained well 2 months following surgery. Gross examination of the stomach showed a polypoidal growth in the lesser curvature measuring 8.06 4.0 cm (Fig. 1). Cut section showed a solid tumour mainly in the submucosa, exhibiting mucoid and haemorrhagic areas. A few enlarged lymph nodes were noted along the greater curvature. Histological examination showed tumour tissue extending from the submucosa up to the serosa of the stomach. The tumour exhibited a plexiform pattern (Fig. 2). The tumour cells were spindle-shaped, with no significant nuclear atypia or mitosis. The stroma comprised of myxoid matrix and was rich in small calibre blood vessels (Fig. 3). The lymph nodes showed reactive changes. Immunohistochemistry showed that the tumour cells were positive for vimentin and smooth muscle actin (SMA) (Fig. 4). A few tumour cells were positive for desmin. They were negative for CD34, S-100 protein and c-kit. Based on the histological features, and supported by the immunostain findings, a diagnosis of PAM was made. Takahashi et al. first reported two cases of gastric tumour which were characterised by plexiform growth pattern, bland spindle cells and myxoid stroma rich in blood vessels. These two unusual tumours were named plexiform angiomyxoid myofibroblastic tumour. In their study, the patients were 50 and 68 years old and the tumours were 4.0–4.5 cm in largest dimension. Our patient was younger (only 23 years old) and the tumour was larger, measuring 8 cm in largest dimension. The histogenesis of PAM is debatable, but it is thought to be of myofibroblastic origin based on the immunohistochemical findings such as positivity for SMA and negativity for desmin, as well as ultrastructural findings. In our case, the tumour was diffusely positive for actin and only focally positive for desmin, indicating focal differentiation towards smooth muscle. Although the clinical follow-up data are minimal in our case, the histological features indicate a benign lesion. The differential diagnoses for spindle cell tumour of the stomach include gastrointestinal stromal tumour (GIST), leiomyoma/sarcoma, inflammatory fibroid polyp and inflammatory myofibroblastic tumour and fibromyxoma. GIST is composed of spindle or epithelioid cells. More than 85% of GISTs are immunoreactive for c-kit. The FIG. 1 The stomach is opened to show a polypoidal growth, measuring 8.06 4.0 cm, situated in the lesser curvature. The tumour has a glistening mucoid and haemorrhagic appearance.

Do Clinical Features and Survival of Single Hormone Receptor Positive Breast Cancers Differ from Double Hormone Receptor Positive Breast Cancers

The significance of the single hormone receptor positive phenotype of breast cancer is still poorly understood. The use of hormone therapy has been found to be less effective for this type, which has a survival outcome midway between double positive and double negative phenotypes. The aim of this study was to investigate differences in patient and tumor characteristics and survival between double-receptor positive (ER+PR+), double receptor negative (ER-PR-) and single receptor positive (ER+PR- and ER-PR+) breast cancer in an Asian setting. A total of 1,992 patients with newly diagnosed stage I to IV breast cancer between 2003 and 2008, and where information on ER and PR were available, were included in this study. The majority of patients had ER+PR+ tumors (n=903: 45.3%), followed by 741 (37.2%) ER-PR-, 247 (12.4%) ER+PR-, and 101 (5.1%) ER-PR+ tumors. Using multivariate analysis, ER+PR- tumors were 2.4 times more likely to be grade 3 compared to ER+PR+ tumors. ER+PR- and ER-PR+ tumors were 82% and 86% respectively less likely to be grade 3 compared with ER-PR- tumors. ER-PR+ tumours were associated with younger age. There were no survival differences between patients with ER+PR+ and ER-PR+ tumors. However, ER+PR- tumors have poorer survival compared with ER+PR+ tumours. ER-PR- tumours had the worst survival. Adjuvant hormonal therapy with tamoxifen was found to have identical survival advantage in patients with ER+PR+ and ER-PR+ tumors whereas impact was slightly lower in patients with ER+PR- tumors. In conclusion, we found ER+PR- tumors to be more aggressive and have poorer survival when compared to ER+PR+ tumors, while patients with ER-PR+ tumours were younger, but had a similar survival to their counterparts with ER+PR+ tumours.

Unusual finding of endocervical-like mucinous epithelium in continuity with urothelium in endocervicosis of the urinary bladder

Endocervicosis in the urinary bladder is a rare benign condition. We present a case in a 37-year-old woman with classical clinical and pathological features of endocervicosis. The unusual observation of endocervical-like mucinous epithelium in continuity with the urothelium in addition to fully developed endocervicosis prompted immunohistochemical profiling of the case using antibodies to cytokeratins (AE1/AE3, CK19, CK7, CK5/6, CK20), HBME-1, estrogen receptor (ER) and progesterone receptor (PR) to assess the relationship of the surface mucinous and endocervicosis glandular epithelia. The surface mucinous epithelium, urothelium and endocervicosis glands were immunopositive for AE1/AE3, CK7 and CK19 while CK20 was only expressed by few urothelial umbrella cells. The surface mucinous epithelium was CK5/6 and HBME-1 immunonegative but showed presence of ER and PR. This was in contrast to the urotheliums expression of CK5/6 but not ER and PR. In comparison, endocervicosis glands expressed HBME-1, unlike the surface mucinous epithelium. The endocervicosis epithelium also demonstrated the expected presence of ER and PR and CK5/6 immunonegativity. The slightly differing immunohistochemical phenotypes of the surface mucinous and morphologically similar endocervicosis glandular epithelium is interesting and requires further clarification to its actual nature. The patient has remained well and without evidence of disease 18-months following transurethral resection of the lesion.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2840395525426177.

Imaging findings of a primary bladder maltoma

Secondary involvement of the urinary bladder in non-Hodgkins lymphoma is relatively common; however, primary malignant lymphoma of this organ is extremely rare. The most common type of primary bladder lymphoma is a low-grade B-cell mucosa-associated lymphoid tissue (MALT) lymphoma. We report here on the imaging findings of a primary bladder lymphoma with bone marrow infiltration.

Cervical abscesses due to co-infection with Burkholderia pseudomallei, Salmonella enterica serovar Stanley and Mycobacterium tuberculosis in a patient with diabetes mellitus

BackgroundInfections due to Mycobacterium tuberculosis, Burkholderia pseudomallei and non-typhoidal Salmonella cause significant morbidity and mortality throughout the world. These intracellular pathogens share some common predisposing factors and clinical features. Co-infection with two of these organisms has been reported previously but, to our knowledge, this is the first time that infection with all three has been reported in one person.Case presentationIn September 2010, a 58-year-old diabetic Malaysian male presented with fever and a fluctuant mass on the right side of his neck. B. pseudomallei was isolated from an aspirate of this lesion and there was radiological evidence of disseminated infection in the liver and spleen. The recurrence of clinical symptoms over ensuing months prompted further aspiration and biopsy of a cervical abscess and underlying lymph nodes. Salmonella enterica serovar Stanley and then M. tuberculosis were identified from these specimens by culture and molecular methods. The patient responded to targeted medical management of each of these infections.ConclusionIn endemic settings, a high index of suspicion and adequate tissue sampling are imperative in identifying these pathogenic organisms. Diabetes was identified as a predisposing factor in this case while our understanding of other potential risk factors is evolving.

Fungal laryngitis causing airway compromise in post irradiated patient

Abstract Fungal laryngeal infection is commonly seen in immunocompromised individuals, and can mimic other laryngeal diseases like gastroesophageal reflux disease, granulomatous disease, leucoplakia and carcinoma. Therefore, it is important for correct initial diagnosis and treatment to avoid morbid consequences. We have reported a patient with laryngeal candidiasis who was previously diagnosed with laryngeal cancer and treated by concurrent chemoradiation therapy, presented with shortness of breath and stridor, requiring an emergency tracheostomy. Laryngoscopy examination revealed the presence of irregular mucosa at the posterior 2/3 of the left vocal cord extending to the left false cord and biopsy taken. Histopathological examination revealed necrotic tissue with colonies of bacteria and Actinomyces, and closer examination revealed fungal organisms exhibiting round, budding structures along with branching hyphae of varying sizes. Special histochemistry with Gomori Methenamine. Silver (GMS) and periodic acid-Schiff (PAS) stains confirmed the presence of fungal bodies. Tissue for culture and sensitivity grew Candida albicans, and the patient treated with IV fluconazole and discharge home with oral fluconazole. Post-treatment follow-up laryngoscopy examination revealed normal laryngeal mucosa with no evidence of fungal bodies or tumours recurrence. A conclusion can be made that diagnosis of a patient with fungal laryngitis requires early detection and treatment, as misdiagnosis or delay in treatment may result in further impairment to the anatomical and functional properties of the larynx. Invasive fungal infection can mimic or hide underlying concomitant laryngeal malignancies. Therefore, performing a biopsy during initial presentation allows the exclusion of underlying malignancy and further progression of the malignancy.