Tuberculous bronchial stenosis: Diagnosis and role of interventional bronchoscopy.

The reported prevalence of tuberculous bronchial stenosis in children is unknown and rarely reported in English-speaking literature. In adult patients with pulmonary tuberculosis, it varies from 40% in an autopsied series in the preantibiotic era to 10% in patients who have undergone routine bronchofibroscopy in modern times. We describe our experience of four cases of confirmed bronchial stenosis due to MTB collected between January 2000 and June 2021 in this case series descriptive study. The diagnosis of bronchial stenosis due to TB was made on flexible bronchoscopy. A TB diagnosis was made if MTB was cultured from respiratory secretions, when Ziehl-Neelsen smear or GeneXpert MTB/RIF test was positive, or if a chest radiograph revealed radiographic features typical of MTB. Bronchial stenosis due to TB is rare even if airway compression is frequently seen. Although an early diagnosis of bronchial stenosis due to TB is difficult on chest X-rays, all children in this series demonstrated parenchymal changes distal to the stenosis ranging from hyperinflation and lobar collaps to bronchiectasis. If bronchial stenosis resulting from TB disease is diagnosed early, balloon dilatation as described in this report, may be an effective and safe intervention, preventing long-term complications such as irreversible lung destruction, that may require pneumonectomy.

Placental pathology in spontaneous and iatrogenic preterm birth: Different entities with unique pathologic features.

INTRODUCTION: Placental pathology is an important contributor to the understanding of preterm birth and reveals major differences between spontaneous preterm birth (SPTB) and iatrogenic preterm birth (IPTB). The aim of this study was to investigate these relationships. METHODS: Research midwives collected placentas from 1101 women with singleton pregnancies who were enrolled in the Safe Passage Study. Trained pathology technologists prepared and processed placenta specimens for macroscopic and microscopic examination by designated pathologists. Statistical analyses were done with STATISTICA version 13. RESULTS: In SPTB we found more cases of accelerated villous maturation; however, the other features of maternal vascular malperfusion (MVM) were not present. The prevalence rate of funisitis was also increased. In IPTB, multiple features of MVM - accelerated villous maturation, distal villous hypoplasia, decidual arteriopathy, increased syncytial knots, increased perivillous fibrin, and prominent extravillous trophoblast were increased, as were features of fetal vascular malperfusion (FVM) - umbilical cord vessel thrombosis, avascular villi, and fetal vascular thrombosis. Increased syncytial knots were found in 26% of preterm stillbirths and in 29% of preterm infant demises as compared to 81% of IPTB infants alive at one year. DISCUSSION: SPTB and IPTB differ. The detected "abnormal" accelerated villous maturation pattern in SPTB and preterm demises, suggests an inability of the placenta to adapt and may be a trigger for SPTB. Funisitis was the only inflammatory response significant for SPTB. MVM and FVM are implicated in IPTB, but not an inflammatory process.

Metastatic olfactory neuroblastoma: A small round blue cell puzzle on fine-needle aspiration cytology.

Small round blue cell tumors (SRBCTs) are a heterogeneous group of malignant neoplasms that can be challenging to distinguish on fine-needle aspiration (FNA) cytology. Ancillary tests as well as clinico-radiological correlation are often required to make an accurate diagnosis. FNA is a low-cost, low-infrastructure test, making it a coveted diagnostic tool, especially in low-resource settings. Olfactory neuroblastoma (ONB) is a rare SRBCT encountered in both pediatric and adult patients. Awareness of the cytomorphologic and immunocytochemical features of ONB is important in the workup of a SRBCT. This case report describes the primary diagnosis of metastatic ONB on FNA cytology.

HIV, Placental Pathology, and Birth Outcomes-a Brief Overview.

The spectrum of placental pathology in human immunodeficiency virus (HIV) is vast. Features observed are not only limited to the effects of the virus itself but may include that of coinfections such as tuberculosis and syphilis. The presence of other comorbidities and changes as a result of antiretroviral therapy may further confound the histologic findings. There is a paucity of unbiased information of the effects of maternal HIV on the placenta and how these changes relate to birth outcomes. Antiretroviral therapy, now in widespread use, has altered the course of maternal HIV disease and it is unknown whether this has altered the pathophysiology of HIV on the placenta. HIV-associated placental findings that have been most well described include acute chorioamnionitis, low placental weight, and maternal vascular malperfusion, with a tendency towards lower rates of chronic villitis.

Adamantinoma-like Variant of Ewing Sarcoma in the Metatarsal Bone After Chemotherapy: Report of a Case Successfully Treated with Pedicled Osteocutaneous Fibular Transfer.

Adamantinoma-like Ewing sarcoma is a rare variant of Ewing sarcoma with histologic and immunohistochemical evidence of squamous differentiation. This variant most commonly occurs in the head and neck region with a few cases reported in the long bones of the limbs. It may be associated with poorer clinical outcome and could pose a diagnostic challenge, particularly if it occurs in older patients or as a metastatic lesion. We present a case of Ewing sarcoma in the metatarsal of an 11-year-old boy that manifested adamantinoma-like morphology after neoadjuvant chemotherapy. Chemotherapy has been reported to induce neuronal maturation and rhabdoid morphology in cases of Ewing sarcoma, but no reports of treatment-induced squamous differentiation with P40/P63 expression have been demonstrated. This is also the first documented case treated with a pedicled osteocutaneous fibular transfer in a metatarsal malignancy, which is usually treated by either ray or below-knee amputation.

Fine Needle Aspiration Biopsy of Peripheral Lymph Nodes in Children: Practical Experience in a Tertiary Hospital.

BACKGROUND: Peripheral lymphadenopathy occurs often in children; fine needle aspiration biopsy (FNAB) is a commonly performed diagnostic procedure. We describe FNAB use and outcome for peripheral lymphadenopathy in children in a routine clinical setting. METHODS: A retrospective study done at Tygerberg Hospital, Cape Town of children (<13 years) who had an FNAB for lymphadenopathy from July 2012 to June 2014. Demographic, clinical, treatment and follow-up data were retrieved from patient folders; FNAB and special investigation results were obtained from the laboratory database. RESULTS: Of the 173 children, the median age was 37 (interquartile range 13-75) months; 20 (11.5%) were HIV positive. Most FNABs were done in the neck (131; 76%) and axillary areas (34; 20%). FNAB provided a result in 165 (95%) cases; in 8 (5%) children FNAB was insufficient for diagnosis. Mycobacterial aetiology was diagnosed in 84 (49%); 49 (58%) were culture-confirmed (37 Mycobacterium tuberculosis, 10 Mycobacterium bovis BCG, 1 both and 1 non-tuberculous mycobacterium). Reactive lymphadenopathy was diagnosed in 56 (32%), neoplastic disease in 6 (3.5%) and other pathology in 19 (11%) cases. Additional special investigations changed FNAB diagnosis or led to an additional diagnosis in 8 (5%) children. Overall, 70/84 (83%) with mycobacterial aetiology and all neoplastic disease cases received the correct treatment. Follow-up appointments were arranged in 144 (83%) patients. CONCLUSIONS: In a high tuberculosis burden area, a single FNAB provided a diagnosis in most cases in a routine referral setting; FNAB remains a safe and useful investigation. Follow-up of children to initiate appropriate treatment could improve. LAY SUMMARY: Large swollen lymph nodes, especially in the neck, are a common finding in children. Fine needle aspiration biopsy (FNAB) is a commonly used diagnostic procedure and we looked at how well this procedure works in everyday hospital practice. We identified all children <13 years of age over a 2-year period (2012-2014) who had an FNAB done at Tygerberg Hospital, Cape Town, South Africa, and looked how well this procedure performed and what the doctors did with these children. We found 173 children who had an FNAB done. They were generally young children of around 3 years old. With a single FNAB, we could make a diagnosis in 95% of these children. About half of the children had tuberculosis or complications of a BCG vaccine (both caused by mycobacteria), only 4% had a malignancy of some kind, about a third had reactive lymph nodes (usually other mainly local infectious causes) and the rest had other pathology like abscesses. All malignancies and >80% of the mycobacterial pathology cases were correctly managed; the latter could definitely improve.

Endobronchial masses encountered on fine-needle aspiration biopsy: a focus on unusual entities.

Fine-needle aspiration biopsy (FNAB) is a useful technique in the evaluation of central lung tumors which is commonly encountered in clinical cytology practice. Some of these tumors may show endobronchial, polypoid growth which is readily apparent to the endoscopist. Pulmonary salivary gland-type tumors and carcinoid tumors are overall uncommon in the lung, but these tumors tend to occur centrally and show endobronchial involvement. The prognosis of these tumors is generally better than that of small cell or non-small cell carcinomas of the lung and more conservative surgical resection is often indicated. The identification of salient cytological features and a high index of suspicion when considering the differential diagnosis of a central lung tumor is essential to accurate diagnosis. This review focuses on cytological clues as well as ancillary techniques that may be useful to the practicing cytopathologist.

Accuracy of colonic mucosal patterns at contrast enema for diagnosis of Hirschsprung disease.

BACKGROUND: Various patterns of colonic mucosal irregularity have been recorded on contrast enema, each with individually very low sensitivity, but high specificity. OBJECTIVE: To assess the accuracy of the radiologic features of Hirschsprung disease utilising a unifying stratification of any form of colonic mucosal irregularity on contrast enema. MATERIALS AND METHODS: We conducted a retrospective study of children with suspected Hirschsprung disease managed at a tertiary South African hospital from January 2009 through April 2015. Three observers independently reviewed abdominal radiographs and contrast enemas. The enema analysis included a unifying category of any form of colonic mucosal irregularity. Radiologic features were compared with rectal biopsy results. We used descriptive statistics and the Fisher exact test to compare the radiologic features of children with and without Hirschsprung disease. RESULTS: Ninety-two children with median age of 37 days (range 3 days to 11 years) were included; 50 had biopsy-proven Hirschsprung disease. On enema, any mucosal irregularity, a transition zone and recto-sigmoid ratio inversion were associated with Hirschsprung disease (all P<0.01). Mucosal irregularity showed 96% sensitivity (95% confidence interval [CI] 86.3-99.5) and 71.4% specificity (CI 55.4-84.3); a transition zone showed 86% sensitivity (CI 73.3-94.2) and 90.5% specificity (CI 77.4-97.3); and recto-sigmoid ratio inversion showed 78% sensitivity (CI 64.0-88.5) and 83.3% specificity (CI 68.3-93.0). CONCLUSION: Colonic mucosal irregularity on contrast enema has high sensitivity and moderate specificity for Hirschsprung disease.

The utility of TTF-1, napsin A, CK5 and p63 staining in the sub-classification of non-small cell carcinoma of the lung.

BACKGROUND: The potentially curative and/or palliative therapy for non-resectable lung cancer has evolved significantly over the past 2 decades. With the availability of targeted therapies, the need for precise sub-typing of non-small cell lung carcinoma (NCSLC) has become paramount. OBJECTIVES: As there are few data from South Africa, we aimed to determine utility of TTF-1, napsin A, p63 and CK5 immunostaining on fine needle aspiration (FNA) cell block and formalin-fixed paraffin-embedded tissue biopsy specimens in subtyping NSCLC as adenocarcinoma and squamous cell carcinomas. METHODS: All cases of NSCLC diagnosed during a 3-year period were retrospectively identified. All FNA biopsy and formalin-fixed paraffin-embedded cases that were stained with TTF-1, napsin A, CK5 and p63 were collected. A lung cancer registry was used to access and correlate clinical and radiological data. RESULTS: We included 271 cases with diagnoses of adenocarcinoma of the lung (n = 201), squamous cell carcinoma of the lung (n = 53), unspecified NSCLC (n = 8) and other carcinomas (n = 9). TTF-1 and napsin A had sensitivities of 99.0% and 91.9%, respectively, positive predictive values (PPVs) of 90.8% and 90.3%, respectively, and accuracies of 91.0% for adenocarcinoma of the lung. Napsin A had a higher specificity than TTF-1 (90.2% vs 62.8%). Both CK5 and P63 had high sensitivities (95.4% and 97.9%, respectively) and negative predictive values of 96.4% and 96.8%, respectively, for squamous cell carcinoma of the lung. CK5 had a higher specificity than p63 (84.4% and 61.2%, respectively), PPV (80.4% and 70.8%, respectively) and accuracy (88.8% and 79.2%, respectively) for squamous cell carcinoma. CONCLUSION: All four immunostaining methods had high sensitivities. TTF-1 and napsin A both had high PPV and diagnostic accuracy for adenocarcinoma of the lung, whereas CK5 had an equally high PPV and accuracy for squamous cell carcinoma of the lung. The specificity of napsin A for adenocarcinoma was higher than that of TTF-1. The specificity of CK5 for squamous cell carcinoma was higher than p63.

Spectrum of Changes Seen With Placental Intravascular Organisms.

Fetal bacterial infections are a common cause of fetal/neonatal morbidity and mortality. The pathologic correlates of congenital bacterial infection include acute chorioamnionitis, acute villitis, and acute intervillositis. The strength of the association of congenital bacterial infection differs among these pathologies. Acute chorioamnionitis results usually from an ascending infection, and damage to the fetus is thought to be cytokine driven rather than damage secondary to bacteremia. Acute villitis is strongly associated with fetal sepsis due to congenital infections. A much less common variant on acute villitis pattern has been described with additional presence of bacteria in the fetal capillaries of the chorionic villi. We describe the spectrum of bacteria that would induce this unique pattern. The histological archives were searched from 2 institutions for cases with intravascular bacteria present in the villous capillaries of the placenta. Thirteen cases were identified, of which 11 cases had acute chorioamnionitis and all cases showed an acute villitis. Eight cases had Escherichia coli identified and 3 cases had Group B Streptococcus. All cases were associated with fetal death. In 9 cases, the mother showed signs of a significant infection including 1 maternal death. We conclude that finding intravascular bacteria is a serious complication of congenital infection with serious fetal and maternal sequela.

Successful Introduction of Fine Needle Aspiration Biopsy for Diagnosis of Pediatric Lymphadenopathy.

Accurate and rapid diagnosis of extrapulmonary nodal tuberculosis in children is of paramount importance. This retrospective study performed at Tygerberg Hospital using data from the laboratory records between January 1, 2004 and June 30, 2014 demonstrates how since the introduction laboratory-run FNAB service; fine needle aspiration biopsy has become an acceptable and routine diagnostic procedure for triage of pediatric lymphadenopathy.

Ultrathin bronchoscopy for solitary pulmonary lesions in a region endemic for tuberculosis: a randomised pilot trial.

BACKGROUND: The evaluation of solitary pulmonary lesions (SPL) requires a balance between procedure-related morbidity and diagnostic yield, particularly in areas where tuberculosis (TB) is endemic. Data on ultrathin bronchoscopy (UB) for this purpose is limited. To evaluate feasibility and safety of UB compared to SB for diagnosis of SPL in a TB endemic region. METHODS: In this prospective randomised trial we compared diagnostic yield and adverse events of UB with standard-size bronchoscopy (SB), both combined with fluoroscopy, in a cohort of patients with SPL located beyond the visible range of SB. RESULTS: We included 40 patients (mean age 55.2 years, 45 % male) with malignant SPL (n = 16; 40 %), tuberculous SPL (n = 11; 27.5 %) and other benign SPL (n = 13; 32.5 %). Mean procedure time in UB and SB was 30.6 and 26.0 min, respectively (p = 0.15). By trend, adverse events were recorded more often with UB than with SB (30.0 vs. 5.0 %, p = 0.091), including extensive coughing (n = 2), blocked working channel (n = 2), and arterial hypertension requiring therapeutic intervention (n = 1), all with UB. The overall diagnostic yield of UB compared to SB was 55.0 % vs. 80.0 %, respectively (p = 0.18). Sensitivity for the diagnosis of malignancy of UB and SB was 50.0 % and 62.5 %, respectively (p = 0.95). CONCLUSION: UB is not superior to SB for the evaluation of SPL in a region endemic with tuberculosis, when combined with fluoroscopic guidance only. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT02490059 ).

Mediastinal granulomatous lymphadenitis in a population at risk for HIV and tuberculosis.

BACKGROUND: Granulomatous inflammation on transbronchial needle aspirates from mediastinal lymph nodes is an infrequent yet important finding. We determined associations between cytomorphological features and underlying aetiology in an area of high prevalence of HIV-infection and tuberculosis. METHODS: We identified cases with granulomatous inflammation on mediastinal aspirates from January 2003 to July 2010. Cytomorphological features were evaluated and graded according to a simple and reproducible system including the presence, quality (discrete or vague), and number (≤5 or more) of granulomas as well as the presence of necrosis, lymphocytes, multinucleated giant cells, and neutrophils. RESULTS: In 81 patients (36 male, 9 HIV-positive) the final diagnosis was tuberculosis in 37 (46%), sarcoidosis in 40 (49%), fibrosing mediastinitis in 1 (1%), and unknown in 3 (4%). The presence of necrosis (P < 0.001) and neutrophils (P = 0.05) was associated with tuberculosis and numerous discrete granulomas were associated with sarcoidosis (P = 0.03). All HIV-positive patients were diagnosed with tuberculosis. CONCLUSION: Granulomatous disease identified on TBNA from mediastinal lymph nodes is mostly associated with sarcoidosis and tuberculosis. Ancillary investigations for sarcoidosis are appropriate if numerous discrete granulomas are found. Tuberculosis must be excluded if necrosis and neutrophils are present and in HIV-positive individuals, particularly in high-burden areas of tuberculosis.

Rapid diagnosis of pediatric mycobacterial lymphadenitis using fine needle aspiration biopsy.

BACKGROUND: Diagnosis of tuberculosis in children is challenging and fine needle aspiration biopsy (FNAB) is used worldwide in the diagnosis of palpable masses including peripheral lymphadenopathy. Recent studies of the use of nucleic acid amplification such as the Xpert MTB/RIF test on FNAB in adult patients have shown considerable promise. Xpert MTB/RIF allows for the rapid diagnosis of Mycobacterium tuberculosis and identification of rifampicin susceptibility. Studies to date have been predominantly performed in adults. This study aims to determine the accuracy of Xpert MTB/RIF for the detection of M. tuberculosis complex in FNAB from children with clinically suspected mycobacterial lymphadenitis. METHODS: Prospective hospital-based study of children <13 years referred for FNAB at Tygerberg hospital and Dora Nginza hospital, South Africa, for suspected mycobacterial lymphadenitis. Aspirates were performed and the results of the Xpert MTB/RIF test were compared with liquid (mycobacterial growth indicator tube) culture and cytology. RESULTS: FNABs were collected from 110 children and 38 (35%) cases were excluded. Of the 72 cases included in the study, 32 were positive for M. tuberculosis complex on Xpert MTB/RIF, 36 on cytology and 25 were culture positive for M. tuberculosis complex. Compared with the combined reference standard (cytomorphology suggestive of mycobacterial disease with direct visualization of the organism and/or bacteriological culture), Xpert MTB/RIF identified 32 of 40 cases as positive with a sensitivity and a specificity of 80% and 93.8%, respectively. CONCLUSIONS: FNAB and Xpert MTB/RIF enable a rapid diagnosis in pediatric mycobacterial lymphadenitis, expediting appropriate treatment and potentially preventing morbidity and mortality.

Morphologic changes in the placentas of HIV-positive women and their association with degree of immune suppression.

OBJECTIVE: To provide baseline information regarding a possible association between specific histopathologic features of the placentas of HIV-positive women and the degree of immune suppression. METHODS: A prospective single-blinded laboratory-based pilot study was conducted at Tygerberg Hospital, South Africa. The macroscopic and microscopic features of placentas from HIV-positive (n=91) and HIV-negative women (n=89) were compared and recorded using a standard template. Investigators were blinded to the participants' HIV status and CD4-positive cell count. RESULTS: Placentas from the HIV-positive group were characterized by decreased weight and increased number of marginal infarcts relative to the HIV-negative group. The most important microscopic finding was the increased presence of villitis of unknown etiology (VUE) among the group of untreated HIV-positive women with CD4 cell counts of 200 cells/mm(3) or below. CONCLUSION: Both macroscopic and microscopic differences relating to the degree of immune suppression were identified, which seemingly contradicts previous reports. Larger studies are warranted to define the function of antiretroviral therapy and VUE in the mechanism of mother-to-fetus transmission of HIV. Furthermore, the potential role of VUE in the pathophysiology of the compromised immune response observed among HIV-exposed but uninfected infants should be investigated.

An interinstitutional review of the value of FNAB in pediatric oncology in resource-limited countries.

Fine-needle aspiration biopsy (FNAB) has been widely accepted as a reliable diagnostic modality in the general pediatric population, but its role in pediatric oncology still remains elusive. With new treatment protocols subscribing to preoperative chemotherapy, the need for a quick, minimally invasive, and accurate diagnostic procedure has arisen. This study assesses the feasibility of FNAB in childhood malignancies to render a specific diagnosis on which treatment can be initiated. An 11-year retrospective study was done on FNABs in patients 19 years and under referred for clinically malignant mass lesions. Cases were confirmed with histology, immunocytochemistry, flow cytometry, or clinical follow-up. Of the 357 patients referred for FNABs, 36 patients were lost to follow-up and 31 FNABS were inadequate. A total of 290 cases were included in the study, of which 68 (23%) cases were benign and 222 (77%) were malignant. The most frequently occurring tumors were nephroblastoma (68), non-Hodgkin's lymphoma (39), rhabdomyosarcoma (22), Hodgkin's lymphoma (22), and neuroblastoma (22). The sensitivity of the procedure for neoplasia was 96.6%, the specificity 97.0%, positive predictive value 99.0%, and negative predictive value 90.1%, with a diagnostic accuracy of 96.7%. The ability of FNAB to enable a specific diagnosis to be made, that is correct and accurate subtyping of the tumor on which chemotherapy or radiotherapy could be commenced was 75.7%. This study shows that FNAB can be used with confidence to confirm malignancy in children. With clinicoradiological correlation and the aid of ancillary techniques, FNAB allows a rapid and accurate preoperative diagnosis for definitive therapy commencement in most cases.

Fine-needle aspiration cytology of subcutaneous fat necrosis of the newborn: the cytology spectrum with review of the literature.

Subcutaneous fat necrosis of the newborn is a rare, transient panniculitis of full-term infants. Diagnosis is usually made clinically; however, a biopsy is sometimes required. Fine-needle aspiration biopsy (FNAB) offers an alternative to biopsy. The cytology shows a spectrum of changes ranging from clumped lobules of fat with opaque cytoplasm to necrotic aspirates with dispersed fat cells with opaque cytoplasm, foamy macrophages, multinucleated giant cells, lymphocytes, and neutrophils. Radially orientated, refractile, needle-shaped crystals are visible in the cytoplasm of the fat cells and loose lying in the necrotic background. FNAB offers an alternative to biopsy with good results.