Adequacy of cytology and small biopsy samples obtained with rapid onsite evaluation (ROSE) for predictive biomarker testing in non-small cell lung cancer.

Complete biomarker workup of non-small cell lung cancer (NSCLC) specimens is essential for appropriate and timely clinical management decisions. This can be challenging to achieve from small cytology and histology specimens, with increasing numbers of molecular and immunohistochemical biomarkers required. We conducted a 5 year retrospective audit of cases at our institution to assess the diagnostic and biomarker testing adequacy rates, particularly those specimens obtained with rapid onsite evaluation (ROSE), performed by a cytopathologist and a cytology scientist or pathology trainee, including all endobronchial ultrasound guided transbronchial needle aspirations (EBUS-TBNA), CT guided lung fine needle aspirations (FNA) and CT guided lung core biopsies. A total of 5,354 cases were identified, of which 92.2% had sufficient material for diagnosis. Of the 1506 cases identified with a recorded diagnosis of lung adenocarcinoma or NSCLC, not otherwise specified, 1001 (66.5%) had biomarker testing requested. Sufficient material was available in 89.5% of cases for a complete biomarker workup which included EGFR and KRAS mutational testing (all cases), ALK, ROS1 and PD-L1 immunohistochemistry (all cases), and ALK and ROS1 FISH (as required). For EGFR and KRAS mutational testing across both cytology and histology specimens, 99% of cases were sufficient. Of the samples in which a complete biomarker workup was unable to be performed, approximately half were only insufficient due to inadequate numbers of tumour cells for PD-L1 immunohistochemistry. Excluding PD-L1 IHC, 952 (95.1%) of samples obtained with ROSE were sufficient for the remainder of the testing requirements. Next generation sequencing using a 33 gene custom AmpliSeq panel was achieved in up to 72% of cases. In conclusion, small cytology and histology specimens obtained with ROSE are suitable for predictive biomarker testing in NSCLC, although attention needs to be paid to obtaining sufficient cells (>100) for PD-L1 immunohistochemistry.

Mitotically Active Nevus and Nevoid Melanoma: A Clinicopathological and Molecular Study.

ABSTRACT: The distinction between nevoid melanoma and a mitotically active nevus can be challenging at the microscopic level. In this study, we performed cytogenetic testing on a cohort of 25 mitotically active melanocytic proliferations resembling common melanocytic nevus from 25 patients. Based on cytogenetic findings, the lesions were classified as "nevoid melanoma" (n = 13) or "mitotically active nevus" (n = 12). Subsequently, we compared the clinicopathological features between these 2 groups. Nevoid melanomas occurred in older patients (P = 0.007); however, there were no significant differences in gender, size, or anatomical distribution between the 2 groups. Histologically, deep/marginal mitoses (P = 0.006), lack of maturation with depth (P = 0.036), and pseudo-maturation (P = 0.006) were significantly more common in nevoid melanomas. Immunohistochemically, complete loss of p16 was an important divisive feature (P = 0.0004), seen in 70% of nevoid melanomas, and highly correlated with loss of CDKN2A gene (chromosome 9p21). Our findings suggest that such reproducible immunomorphological differences can be of value in distinguishing nevoid melanoma from mitotically active nevus. Nevoid melanomas demonstrated a spectrum of chromosomal aberrations similar to those seen in common subtypes of melanoma, which can serve as a powerful adjunct diagnostic tool in morphologically challenging lesions.

Coronavirus-Associated Coagulopathy: Lessons From SARS-CoV1 and MERS-CoV for the Current SARS-CoV2 Pandemic.

To date, several studies have suggested a severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)-mediated hypercoagulability in the forms of pulmonary embolism, stroke, gangrene, "COVID toes," as well as other acute thrombotic complications, warranting the use of systemic anticoagulation. Currently, there are no definitive recommendations as to the timing and dosing of prophylactic or therapeutic anticoagulation in coronavirus disease 2019 (COVID-19) patients. In this manuscript, we report a case of SARS-CoV2-mediated hypercoagulability and review the literature pertaining to the incidence and pathophysiology of coronavirus-mediated coagulopathies. A 64-year-old female, with a medical history of hypothyroidism and remote tobacco abuse, presented to the ED with fever and nonproductive cough. She had multiple negative SARS-CoV2 nasopharyngeal PCR tests during her hospital stay, but chest imaging and elevated inflammatory markers were suggestive of SARS-CoV2 infection. Computed tomography showed a left upper lobe pulmonary embolism with associated right heart strain, and an enlargement of the main pulmonary artery, for which she was initiated on therapeutic anticoagulation with low molecular weight heparin. Despite the medical management of her pulmonary embolism and conservative management of her SARS-CoV2, her clinical condition worsened requiring intubation and mechanical ventilation. After seven days, she was successfully extubated and was transferred to the medical service where her clinical course remained stable and subsequently discharged home on apixaban. In patients with SARS-CoV1-, SARS-CoV2-, and the Middle East respiratory syndrome coronavirus (MERS-CoV)-mediated hypercoagulability, the risk of thrombosis appears to be multifactorial - direct viral cytopathological effects, a pro-inflammatory state, cytokine storm, hypoxia-inducible thrombosis, and endothelial inflammation culminating in the formation of intra-alveolar or systemic fibrin clots. While initial guidelines have been developed to assist clinicians in selecting appropriate chemoprophylaxis as well as therapeutic anticoagulation, a consensus statement remains lacking. Further studies are needed to evaluate the pathogenesis and treatment of coronavirus-induced thrombosis.

Large nested melanoma: a clinicopathological, morphometric and cytogenetic study of 12 cases.

A group of melanomas characterised by predominant growth as large nests within the epidermis has been described. These cases present a diagnostic challenge, as many traditional architectural criteria for the recognition of melanoma are absent. We report the clinical, histological, immunohistochemical, morphometric and cytogenetic features of a series of 12 cases of large nested melanoma. In this series, large nested melanoma accounted for 0.2% of cases of melanoma. The majority occurred on the trunk of middle aged patients with absent or minimal solar elastosis and 42% were associated with a component of benign intradermal melanocytic naevus, speaking to classification of these melanomas as falling within the spectrum of lesions developing in skin with low cumulative sun damage. In 67% of cases invasive melanoma was present. Criteria such as asymmetry, variation in nest size and intraepidermal nests with an underlying rim of junctional keratinocytes appear to be highly specific, and are strongly predictive of typical cytogenetic abnormalities of melanoma, which were identified in 92% of cases. Conversely, in addition to features which are definitionally absent or limited, features such as solar elastosis and cytological atypia do not appear to be particularly helpful in recognition of this variant.

A novel 2.3 mb microduplication of 9q34.3 inserted into 19q13.4 in a patient with learning disabilities.

Insertional translocations in which a duplicated region of one chromosome is inserted into another chromosome are very rare. We report a 16.5-year-old girl with a terminal duplication at 9q34.3 of paternal origin inserted into 19q13.4. Chromosomal analysis revealed the karyotype 46,XX,der(19)ins(19;9)(q13.4;q34.3q34.3)pat. Cytogenetic microarray analysis (CMA) identified a ~2.3Mb duplication of 9q34.3 → qter, which was confirmed by Fluorescence in situ hybridisation (FISH). The duplication at 9q34.3 is the smallest among the cases reported so far. The proband exhibits similar clinical features to those previously reported cases with larger duplication events.

Effect of ampicillin and chloroquine on humoral immune response elicited by bovine albumin encapsulated in liposomes.

Immune suppression resulting from chemoprophylaxis and potential drug interaction were investigated in experimental animals pre-medicated with ampicillin and chloroquine followed by immunization with bovine serum albumin bearing liposomes prepared by the reverse phase evaporation method. The prepared liposomes were evaluated for particle size, entrapment efficiency and in vitro release. Humoral immune response was measured in terms of systemic IgG antibody titre by the ELISA method. The present study showed that 7:3 molar ratio of soya phosphatidylcholine and cholesterol produced liposomes of mean diameter of 235.4 +/- 10.3 nm and entrapment efficiency of 41.3 +/- 3.2%. Ampicillin significantly (p < 0.05) decreased the antibody titre whereas chloroquine did not reduce the antibody titre significantly. The study will help in programming a new drug management and in characterization of vaccine-drug interaction.

Peroperative Gastrograffin bowel lavage in gastroschisis.

AIMS: The aim of the study was to evaluate potential benefits in the use of peroperative bowel lavage with Gastrograffin in neonates with gastroschisis. METHODS: A retrospective analysis of newborns with gastroschisis was performed over a 10-year period in 2 centers in the United Kingdom. Two groups were studied wherein one had peroperative bowel lavage with Gastrograffin and the other did not. RESULTS: Data were collected on 116 patients of whom 93 were suitable for analysis. There were no statistically significant differences in primary closure rate, duration of ventilation, parenteral nutrition, or hospital stay. Intestinal obstruction occurred more frequently in the nonlavage group. CONCLUSION: Gastrograffin lavage peroperatively in gastroschisis offers no potential advantage in reducing ventilatory requirements, parenteral nutrition, and hospital stay. It also does not achieve greater primary closure rates, but may reduce the incidence of intestinal obstruction.