Bethy S. Hernowo

Decidual infiltration of FoxP3+ regulatory T cells, CD3+ T cells, CD56+ decidual natural killer cells and Ki-67 trophoblast cells in hydatidiform mole compared to normal and ectopic pregnancies

Hydatidiform moles are considered pre-cancerous lesions of gestational trophoblastic neoplasia and are associated with an aberrant immune response. This preliminary study aimed to evaluate the feasibility of measuring the presence of immune cells as potential prognostic markers for hydatidiform moles. Immunohistochemical staining of FoxP3⁺ regulatory T cells, CD3⁺ T cells, CD56⁺ decidual natural killer cells and Ki-67⁺ trophoblast cells was performed on 32 samples. Samples were from complete hydatidiform moles, partial hydatidiform moles, ectopic pregnancies, gestational age-matched normal elective pregnancy terminations (normal pregnancies) and gestational trophoblastic neoplasias. FoxP3⁺ regulatory T-cell infiltration was highest in the complete hydatidiform moles and lowest in the normal pregnancy samples. The normal pregnancy cases showed significantly fewer FoxP3⁺ regulatory T cells compared to the ectopic pregnancy cases (p=0.037) and compared to the combination of all of the other groups (p=0.044). Normal pregnancy samples also showed the lowest infiltration of CD3⁺ T cells and the highest number of CD56⁺ decidual natural killer cells; conversely, gestational trophoblastic neoplasias showed the highest infiltration of CD3⁺ T cells and the lowest number of CD56⁺ decidual natural killer cells. The numbers of Ki-67⁺ trophoblast cells were highest in the gestational trophoblastic neoplasias (688/1,000 trophoblast cells) and lowest in the partial moles (87/1,000 trophoblast cells). Our results suggest that regulatory T cells may be involved in the progression of complete hydatidiform moles. A larger cohort study is required to assess whether immune cells are effective prognostic markers in gestational trophoblastic diseases.

Human Papillomavirus Genotypes Profile in Cervical Cancer Patients at Dr. Hasan Sadikin General Hospital, Bandung, Indonesia

BACKGROUND As in other developing countries, cervical cancer is the most frequent gynecologic malignancy in Indonesia. Persistent high risk genotypes of human papillomavirus (HPV) that infect the cervical tissue have been established as the etiology of cervical cancer. This study aimed to explore the profile of cervical cancer patients and the infected HPV genotypes at Dr. Hasan Sadikin General Hospital-Bandung. MATERIALS AND METHODS During the year 2010, 554 cervical cancer patients were registered. In a subset of the patients during July-November 2010, 40 randomized fresh biopsies were tested for HPV genotype after obtained informed consent. The distribution of HPV genotypes and the association to risk factors were analysed. RESULTS The result showed that 62.5% of the tested biopsies were infected by multiple HPV infections, with HPV-16 found in most of the cervical cancer patients (90%). Marriage at age younger than 16 years old was statistically significant in relation to multiple HPV infection (p=0.003), but not parity more than three times (p=0.59). CONCLUSIONS Although high paritiy in our study was not associated with multiple HPV infection, good family planning programs and reproductive health education need to be emphasized in Indonesia as high parity and marriage at young age might increase the chance of cervical cancer development.

Giant cell angiofibroma of the scalp: A benign rare neoplasm with bone destruction.

Background: The incidence of extraorbital giant cell angiofibroma (GCA) is rare, with only one case located in the scalp reported in the literature. The morphological hallmark is histopathological examination showing richly vascularized pattern-less spindle cell proliferation containing pseudovascular spaces and floret-like multinucleate giant cells. Case Description: We report a case of a 30-year-old female with a primary complaint of a painless solitary nodule arising on the left parietal region of the scalp. Complete tumor removal through surgical intervention was achieved, and the postoperative period was uneventful. Conclusion: Diagnosing a highly vascularized tumor in the head and neck is challenging. Our case is unique in that it is presented as a GCA of the scalp, which is an extremely rare clinical entity, and also demonstrated bone destruction.

The Role of Osteocalcin and Alkaline Phosphatase Immunohistochemistry in Osteosarcoma Diagnosis

Background The diagnosis of Osteosarcoma (OSA) is not always straightforward. OSA may resemble Other Primary Bone Tumours (OPBT). The diagnosis of osteosarcoma is sometimes difficult especially in a very small specimen. Immunohistochemistry is one of ancillary testing types that can help the diagnosis of many tumours. The aim of this study was to evaluate the validity of Osteocalcin (OCN) and Alkaline Phosphatase (ALP) immunohistochemistry in discriminating OSA from OPBT. Method This study included 50 selected human primary bone tumours, 25 cases of OSA and 25 cases of OPBT. Immunohistochemical evaluation of OCN and ALP was done for all cases. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were calculated. Result The mean age of OSA and OPBT patients was 19.6 ± 13.6 and 40.0 ± 16.3 years, respectively. Osteocalcin was positive in 17/25 (68%) cases of OSA and 16/25 (64%) cases of OPBT (p = 0.061). Alkaline Phosphatase was positive in 24/25 (96%) cases of OSA and 5/25 (20%) cases of OPBT (p < 0.001). The sensitivity of OCN in OSA diagnosis was 68%, with specificity, PPV, NPV, and overall accuracy being 36%, 52%, 53%, and 52%, respectively. The sensitivity of ALP in OSA diagnosis was 96%, with specificity, PPV, NPV, and overall accuracy being 80%, 82.7%, 95.2%, and 88%, respectively. Conclusion ALP immunohistochemistry is useful in discriminating OSA from OPBT. ALP is superior to OCN in OSA diagnosis. OCN cannot be used to differentiate between OSA and OPBT.

The Major Role of NF-κB in the Depth of Invasion on Acral Melanoma by Decreasing CD8 + T Cells

Background The tumor microenvironment including immune surveillance affects malignant melanoma (MM) behavior. Nuclear factor κB (NF-κB) stimulates the transcription of various genes in the nucleus and plays a role in the inflammatory process and in tumorigenesis. CD8+ T cells have cytotoxic properties important in the elimination of tumors. However, inhibitory receptors on the cell surface will bind to programmed death-ligand 1 (PD-L1), causing CD8+ T cells to lose their ability to initiate an immune response. This study analyzed the association of NF-κB and PD-L1 expression levels and CD8+ T-cell counts with depth of invasion of acral MM, which may be a predictor of aggressiveness related to an increased risk of metastasis. Methods A retrospective cross-sectional study was conducted in the Department of Anatomical Pathology, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin Hospital using 96 cases of acral melanoma. Immunohistochemical staining was performed on paraffin blocks using anti–NF-κB, –PD-L1, and -CD8 antibodies and invasion depth was measured using dotSlide-imaging software. Results The study showed significant associations between the individual expression of NF-κB and PD-L1 and CD8+ T-cell number, with MM invasion depth. NF-κB was found to be a confounding variable of CD8+ T-cell number (p < .05), but not for PD-L1 expression (p = .154). Through multivariate analysis it was found that NF-κB had the greatest association with the depth of invasion (p < .001), whereas PD-L1 was unrelated to the depth of invasion because it depends on the number of CD8+ T cells (p = .870). Conclusions NF-κB plays a major role in acral MM invasion, by decreasing the number of CD8+ T cells in acral MM.

Expression of the RAC1, RHOA and CXCR4 proteins and their interaction as risk factors for infiltration to the nipple areola complex in operable breast carcinoma

BackgroundNipple areola complex (NAC) infiltration in operable breast carcinoma (OBC) is associated with local recurrence. NAC infiltration in OBC suggests that RAC1, RHOA and CXCR4 proteins are risk factors for migration and infiltration of OBC to NAC. This study aims to analyze the expression and interactions of these proteins as risk factors for NAC infiltration in OBC.Materials and methodsThis is an analytic observational cross-sectional study coupled with a categorical comparative study in each 40 subjects of OBC with and without NAC infiltration. The immunohistochemistry performed with a cut-off point based on the result of a receiver operating characteristics (ROC).ResultsRAC1, p < 0.001 with POR 5.76, 95% CI: 2.06–16.08; RHOA, p < 0.001 with POR 7.00, 95% CI: 2.28–21.53; and CXCR4, p = 0.001 with POR 6.33, 95% CI 2.06–19.49. There was an interaction between RAC1 and RHOA (p < 0.001 with POR 17.14, 95% CI: 3.07-125.66); between RAC1 and CXCR4 (p < 0.001 with POR 30.93, 95% CI 3.62–686.89); between RHOA and CXCR4 (p < 0.001 with POR 10.21, 95% CI 2.19–54.17); and between the RAC1, RHOA and CXCR4 proteins (p < 0.001 with POR = 23.69, 95% CI 2.51–544.86).ConclusionWe conclude that the expression of the RAC1, RHOA, and CXCR4 proteins and their interactions play a role as risk factors of NAC infiltration.

Adult medulloblastoma: A rare case report and literature review

Background: Medulloblastoma is a highly malignant embryonal tumor which commonly arises in the cerebellum. It is relatively rare and accounts for less than 2% of all primary brain tumors. The tumor primarily occurs in childhood; however, rarely, it may be found in adult population. In addition, medulloblastoma in adult population shows features which are quite distinct from the pediatric group. Case Description: We report the case of a 33-year-old man who presented to our institution with a history of blurred vision of both eyes for 5 months preceded by intermittent headache since the previous year. Preoperative investigation suggested a posterior fossa mass and we suspected an ependymoma. The patient underwent ventriculoperitoneal shunt and craniotomy tumor removal, followed by radiotherapy. Histopathological and immunohistochemical examination were performed, and the results showed a diagnosis of medulloblastoma. Conclusion: This case is exceptional because adult medulloblastoma occurrence in our center is extremely rare, and the diagnosis can only be established through histopathological and immunohistochemical studies.

Bcl-2 Immunoexpression as Radiotherapy Response Predictor in Undifferentiated Nasopharynx Carcinoma

Nasopharyngeal carcinoma ( N PC) is an epithelial malignancy originating from the surface of the lateral and posterior wall of the nasopharynx. Bcl-2 is an oncoprotein that plays an important role in disrupting the process of apoptosis. Expression of Bcl-2 in biopsy samples of undifferentiated NPC also related to the nature of more aggressive tumor mass and unfavorable clinical radiotherapy response. The purpose of this study was to assess the relationship of Bcl-2 expression with radiotherapy response in undifferentiated NPC. The method of this study areusing 40 samples of paraffin blocks were diagnosed as undifferentiated NPC by histopathologic examination with H&E staining. The samples were divided into 2 groups who respond and do not respond to radiotherapy. All samples examined by Bcl-2 immunohistochemistry and the expression willanalyzed and assess therelationship to radiotherapy response. Of the 40 cases of undifferentiated NPC show imunoekspresi Bcl-2 positive in 39 cases (97.5%) and 1 case (2.5%) negative from response group. The results of statistical analysis of the Bcl-2 obtained significant results with p value <0.05 so we can conclude there is a relationship between Bcl-2 expression with radiotherapy response. Conclusion, Bcl-2 can be used as a predictor for the success of radiotherapy in undifferentiated NPC. Keywords: Bcl-2, undifferentiated NPC, radiotherapy response

A rare giant scalp dermatofibrosarcoma protuberans.

Background: Giant dermatofibrosarcoma protuberans (DFSP) of the scalp is a rare case, which is an intermediate grade soft tissue neoplasm originating from the dermal layer of the skin, which usually occurs in adults. Case Description: We describe such a case in a 26-year-old male. A wide local excision of the tumor with a generous tissue margin was performed; microscopic and immunohistochemical findings established the diagnosis of recurrent DFSP. Conclusion: Our case is unique in that it is presented as a dermatofibrosarcoma protuberans of the scalp, which is an extremely rare clinical entity, and the patient remains well after 14 months with no further treatment, without any tumor recurrence.