Drug concentration at the site of disease in children with pulmonary tuberculosis.

BACKGROUND: Current TB treatment for children is not optimized to provide adequate drug levels in TB lesions. Dose optimization of first-line antituberculosis drugs to increase exposure at the site of disease could facilitate more optimal treatment and future treatment-shortening strategies across the disease spectrum in children with pulmonary TB. OBJECTIVES: To determine the concentrations of first-line antituberculosis drugs at the site of disease in children with intrathoracic TB. METHODS: We quantified drug concentrations in tissue samples from 13 children, median age 8.6 months, with complicated forms of pulmonary TB requiring bronchoscopy or transthoracic surgical lymph node decompression in a tertiary hospital in Cape Town, South Africa. Pharmacokinetic models were used to describe drug penetration characteristics and to simulate concentration profiles for bronchoalveolar lavage, homogenized lymph nodes, and cellular and necrotic lymph node lesions. RESULTS: Isoniazid, rifampicin and pyrazinamide showed lower penetration in most lymph node areas compared with plasma, while ethambutol accumulated in tissue. None of the drugs studied was able to reach target concentration in necrotic lesions. CONCLUSIONS: Despite similar penetration characteristics compared with adults, low plasma exposures in children led to low site of disease exposures for all drugs except for isoniazid.

Multinational, Multicenter Evaluation of Prostate Cancer Tissue in Sub-Saharan Africa: Challenges and Opportunities.

PURPOSE: Prostate cancer disproportionately affects men of African descent, yet their representation in tissue-based studies is limited. This multinational, multicenter pilot study aims to establish the groundwork for collaborative research on prostate cancer in sub-Saharan Africa. METHODS: The Men of African Descent and Carcinoma of the Prostate network formed a pathologist working group representing eight institutions in five African countries. Formalin-fixed paraffin-embedded prostate tissue specimens were collected from Senegal, Nigeria, and Ghana. Histology slides were produced and digitally scanned. A central genitourinary pathologist (P.L.) and eight African general pathologists reviewed anonymized digital whole-slide images for International Society of Urological Pathology grade groups and other pathologic parameters. Discrepancies were re-evaluated, and consensus grading was assigned. A virtual training seminar on prostate cancer grading was followed by a second assessment on a subcohort of the same tissue set. RESULTS: Of 134 tissue blocks, 133 had evaluable tissue; 13 lacked cancer evidence, and four were of insufficient quality. Post-training, interobserver agreement for grade groups improved to 56%, with a median Cohen's quadratic weighted kappa of 0.83 (mean, 0.74), compared with an initial 46% agreement and a quadratic weighted kappa of 0.77. Interobserver agreement between African pathologist groups was 40%, with a quadratic weighted kappa of 0.66 (95% CI, 0.51 to 0.76). African pathologists tended to overgrade (36%) more frequently than undergrade (18%) compared with the reference genitourinary pathologist. Interobserver variability tended to worsen with a decrease in tissue quality. CONCLUSION: Tissue-based studies on prostate cancer in men of African descent are essential for a better understanding of this common disease. Standardized tissue handling protocols are crucial to ensure good tissue quality and data. The use of digital slide imaging can enhance collaboration among pathologists in multinational, multicenter studies.

A rare case of small-cell neuroendocrine tumour of the lung metastasising to the urinary bladder.

A 77-year-old woman with suspected lung carcinoma had multiple bladder masses and lymphadenopathy outside the normal urinary bladder drainage area. Fine needle aspiration and immunocytochemistry of the cervical lymph node complex and transurethral biopsy of the bladder masses confirmed metastatic small-cell neuroendocrine carcinoma. Contribution: Clinical correlation, imaging findings, tumour markers and immunohistochemistry are necessary for metastatic bladder tumour work-up.

Merkel cell carcinoma of the anorectum: a case report and review of the literature.

Merkel cell carcinoma is a highly aggressive neuroendocrine carcinoma that most commonly arises in sun-exposed skin. Established risk factors include advanced age, fair skin, chronic ultraviolet light exposure and immunosuppression. Merkel cell polyomavirus infection is implicated in a subset of cases. Primary extracutaneous Merkel cell carcinoma is exceedingly rare. We report a case of Merkel cell carcinoma of the anorectum in a 44-year-old woman of Indian descent with no apparent risk factors. She presented with rectal bleeding and worsening perineal discomfort. A polypoid tumor was identified in the anal canal. No cutaneous lesions were detected. Histopathology revealed a small round blue cell tumor with neuroendocrine features. Immunohistochemistry for CK20, synaptophysin, CD56, neurofilament and SATB2 were positive while CK7, CDX2 and TTF1 were negative. Polymerase chain reaction and immunohistochemistry were negative for Merkel cell polyomavirus. Merkel cell carcinoma should be considered in the differential diagnosis of a high grade neuroendocrine carcinoma at an unusual site such as the anorectum in this case. Correct diagnosis of Merkel cell carcinoma at an extracutaneous site is crucial because it should prompt careful evaluation for a skin primary and it may make the patient eligible for immune checkpoint inhibitor therapy.

The Prevalence of Human Papillomavirus-Positive Oropharyngeal Squamous Cell Carcinoma at One of the Largest Tertiary Care Centers in Sub-Saharan Africa.

CONTEXT.­: Limited data exist on the prevalence of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma in sub-Saharan Africa. OBJECTIVE.­: To determine the prevalence of HPV-positive oropharyngeal squamous cell carcinoma at a large tertiary care center in South Africa. DESIGN.­: A total of 266 oropharyngeal squamous cell carcinomas diagnosed during an 11-year period (2007-2017) were selected for evaluation. Cases staining positive for p16 immunohistochemistry were evaluated for high-risk HPV using the BD Onclarity assay (BD Diagnostics, Sparks, Maryland). RESULTS.­: Of 266 oropharyngeal squamous cell carcinomas, 14% (n = 36) were positive for p16. Polymerase chain reaction for high-risk HPV performed on the p16-positive cases was negative in 23 cases and positive in 13 cases (13 of 266; 5%). p16 showed a positive predictive value of 36.1%. The HPV subtypes were HPV-16 (n = 10), HPV-18 (n = 1), HPV-52 (n = 1), and HPV-31 (n = 1). Human papillomavirus-positive cases occurred in 10 men and 3 women (mean age, 51 years) and arose from the tonsil (n = 10) or base of the tongue (n = 3). The HPV-positive cases were non-keratinizing (n = 10) or partially keratinizing (n = 1). Partially/nonkeratinizing cases revealed a modest improvement in p16 positive predictive value (11 of 21; 52.4%). CONCLUSIONS.­: The presence of high-risk HPV in 5% of cases suggests that high-risk HPV is a minor etiologic agent in oropharyngeal squamous cell carcinoma in this region. Given its suboptimal positive predictive value, p16 is not a reliable marker for high-risk HPV infection in this region. When p16 is positive, HPV-specific testing is necessary. The identification of less common high-risk HPV types, HPV-52 and HPV-31, may influence current local vaccination strategies.

Lymphomatoid granulomatosis: a rare cause of cavitatory lung disease in an HIV positive child.

We present an unusual cause of lung cavitation and a neck mass in an HIV positive child, initially thought to be tuberculosis. This case report illustrates that the cause for cavitatory lung disease in immunosuppressed children has a large number of possibilities and careful investigation to determine the etiological agent is warranted.

Inflammatory myofibroblastic tumor of the bladder in a 3-year-old boy.

Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm with unknown malignant potential that has been described in most organ systems. We present the case of a 3-year-old boy who was referred with lower urinary tract symptoms and macroscopic hematuria. An IMT was suspected after clinical, radiological, and surgical work-up, and the diagnosis was confirmed after a partial cystectomy was performed. A bladder-preserving approach is the treatment of choice, but close clinical follow-up is recommended because of the unknown biological behavior of these tumors.

Rare case of perplexing ovarian endometriosis.

OBJECTIVE: To document a rare case of coexisting endometriosis and mature cystic teratoma in the same ovary. DESIGN: Case report. SETTING: Gynecology unit in a tertiary training and teaching hospital in Cape Town, South Africa. PATIENT(S): A 30-year-old healthy nulligravida woman with a large ovarian tumor. INTERVENTION(S): After a basic examination, a diagnostic and management laparotomy was performed. A unilateral oophorectomy and staging laparotomy were performed. MAIN OUTCOME MEASURE(S): Final diagnosis of a complex ovarian tumor. RESULT(S): Histologic analysis confirmed endometriosis of the pelvis and concomitant compound pathology in the right ovary, which included endometriosis, mature teratoma, and mucinous cystadenoma. CONCLUSION(S): Co-existence of varied pathology in a single organ presents a challenge to the pathologist and the clinician. Accurate clinical (i.e., surgical) assessment and decisive histologic verification forms a critical part in this process. This case of coexisting endometriosis and teratoma in a single ovary is, to our knowledge, only the third case reported in literature.