Tracheal chondrosarcoma: A case report, systematic review, and pooled analysis.

BACKGROUND: Tracheal chondrosarcoma is a rare malignancy, and formal treatment guidelines have not been established due to the lack of high quality studies. Best evidence at this time is limited to case reports. AIM: Explore the role of surgical intervention, radiation therapy, and chemotherapy, and the long-term outcomes for these interventions for tracheal chondrosarcoma. METHODS AND RESULTS: A literature search was performed using PubMed (1959-2020) and ResearchGate (1959-2020) using medical subject heading terms "tracheal chondrosarcoma" OR "trachea chondrosarcoma." Additional reports were identified within reviewed articles and included for review. Articles pertaining to chondrosarcomas of the lung, bronchus, larynx, or other head and neck subsites were excluded. Cases of chondromas were excluded. Thirty-five patients with tracheal chondrosarcoma were identified in the literature since 1959. Advanced age was significantly associated with recurrent or persistent disease (p = .003). The majority (77%) of cases were treated with open surgical resection, with an open approach and negative surgical margins being significantly associated with being disease-free after treatment (p = .001 and p < .001, respectively). Adjuvant radiotherapy was reserved for those unfit for surgery or for recurrent disease. Tumor size, extra-tracheal extension, tumor calcification, location, and initial diagnosis were not associated with tumor recurrence. CONCLUSION: Non-metastatic tracheal chondrosarcoma can be treated by adequate surgical resection, with little to no role for adjuvant radiotherapy or chemotherapy. Open surgery and negative margins were associated with oncologic control, while advanced age was associated with recurrent or persistent disease.

Molecular and Immunohistochemical Analysis of Mucinous Cystic Neoplasm of the Liver.

OBJECTIVES: Mucinous cystic neoplasm of the liver is characterized by neoplastic mucinous and/or biliary epithelium surrounded by ovarian-type stroma. Immunohistochemical studies have shown that the ovarian-type stroma expresses estrogen receptor, suggesting potential hormonal responsiveness. The molecular biology of mucinous cystic neoplasm of the liver remains poorly studied. METHODS: Transcriptome sequencing and immunohistochemistry were performed on a series of mucinous cystic neoplasms. RESULTS: Mucinous cystic neoplasm of the liver exhibited significantly increased RNA expression of ovarian stromal markers WT1, PR, and ER2 and sex cord stromal markers SF-1, inhibin-α, and calretinin compared with nonneoplastic liver. Immunohistochemistry confirmed the RNA-level data. Evidence for sex hormone biosynthesis was identified by significant overexpression of multiple estrogen biosynthetic enzymes. Expression of 17ß-hydroxysteroid dehydrogenase 1 was confirmed immunohistochemically. Pathway analysis also identified significant upregulation of the hedgehog and Wnt pathways and significant downregulation of T-helper 1 and T-helper 2 pathways. CONCLUSIONS: Mucinous cystic neoplasm of the liver recapitulates ovarian stroma at the morphologic, DNA, RNA, and protein levels. These data support the concept that this tumor likely arises from ectopic primitive gonadal tissue and/or stromal cells with capacity to transdifferentiate to ovarian cortical cells.

A monoclonal antibody against SV40 large T antigen (PAb416) does not label Merkel cell carcinoma.

AIMS: Merkel cell carcinoma represents poorly differentiated neuroendocrine carcinoma of cutaneous origin. In most studies, the vast majority of Merkel cell carcinomas are Merkel cell polyomavirus (MCPyV)-associated. SV40 polyomavirus immunohistochemistry is typically used in the diagnosis of other polyomavirus-associated diseases, including tubulointerstitial nephritis and progressive multifocal leukoencephalopathy, given cross-reactivity with BK and JC polyomaviruses. MCPyV-specific immunohistochemistry is commercially available, but, if antibodies against SV40 also cross-reacted with MCPyV, that would be advantageous from a resource-utilisation perspective. METHODS AND RESULTS: Tissue microarrays were constructed from 39 Merkel cell carcinomas, 24 small-cell lung carcinomas, and 18 extrapulmonary visceral small-cell carcinomas. SV40 large T antigen immunohistochemistry (clone PAb416) was performed; MCPyV large T antigen immunohistochemistry (clone CM2B4) had been previously performed. UniProt was used to compare the amino acid sequences of the SV40, BK, JC and MCPyV large T antigens, focusing on areas recognised by the PAb416 and CM2B4 clones. SV40 immunohistochemistry was negative in all tumours; MCPyV immunohistochemistry was positive in 38% of Merkel cell carcinomas and in 0% of non-cutaneous poorly differentiated neuroendocrine carcinomas. UniProt analysis revealed a high degree of similarity between SV40, BK, and JC viruses in the region recognised by PAb416. There was less homology between SV40 and MCPyV in this region, which was also interrupted by two long stretches of amino acids unique to MCPyV. The CM2B4 clone recognises a unique epitope in one of these stretches. CONCLUSIONS: The PAb416 antibody against the SV40 large T antigen does not cross-react with MCPyV large T antigen, and thus does not label Merkel cell carcinoma.

Clusterin in Neuroendocrine Epithelial Neoplasms: Absence of Expression in a Well-differentiated Tumor Suggests a Jejunoileal Origin.

Clusterin, a widely expressed, tissue-specific glycoprotein, is a diagnostic marker of several tumor types, including anaplastic large cell lymphoma, follicular dendritic cell sarcoma, and tenosynovial giant cell tumor. A recent study has suggested it is highly expressed by well-differentiated neuroendocrine tumors (NET) arising at most anatomic sites, with the exception of jejunoileal tumors, and that it is similarly not expressed by poorly differentiated neuroendocrine carcinomas (NEC). We sought to validate this result in a large cohort of NETs and NECs. Clusterin immunohistochemistry was performed on tissue microarrays of 255 NETs [45 lung, 4 stomach, 8 duodenum, 75 pancreas (62 primary, 13 metastatic), 107 jejunoileum (69 primary, 38 metastatic), 16 appendix] and 88 NECs (43 visceral, 45 Merkel cell). Extent (%) and intensity (0, 1+, 2+, 3+) of staining were assessed and an H-score (extent x intensity) calculated. An average H-score >5 was considered positive. Clusterin expression was noted in 82.4% of 148 nonjejunoileal NETs (average H-score 183) and only 8.4% of 107 jejunoileal NETs (average H-score, 31), as well as 19.3% of NECs (average H-score, 36). Clusterin is frequently, strongly expressed by NETs of diverse anatomic sites, with the exception of jejunoileal tumors, in which it is only rarely, weakly expressed. It is occasionally, weakly expressed by NECs. Most metastatic NETs of occult origin arise in the pancreas or the jejunoileum. For cases in which an initial site of origin immunopanel (eg, islet 1, PAX6, CDX2) is ambiguous, addition of clusterin may be diagnostically useful, with absence of expression suggesting a jejunoileal origin.

Plexogenic pulmonary hypertension associated with POEMS syndrome.

Pulmonary hypertension is one of the well-known clinical manifestations of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, occurring in approximately 25-30% of the affected individuals. However, the histopathologic spectrum of pulmonary hypertension associated with POEMS syndrome has not been fully documented in the literature. Herein, we report an autopsy case of POEMS syndrome in a patient whose lung tissues showed histopathology indistinguishable from that of idiopathic pulmonary arterial hypertension with abundant plexiform lesions in the small pulmonary arteries.

The Almost-Normal Liver Biopsy: Presentation, Clinical Associations, and Outcome.

Liver biopsies obtained for abnormal liver enzymes or unexplained ascites occasionally appear histologically almost normal. The differential diagnosis for these cases is challenging because literature addressing this topic is lacking. We aimed to establish a differential diagnosis and determine clinical associations and outcomes for almost-normal liver biopsies. Ninety-seven histologically almost-normal liver biopsies were collected from 2 institutions. All cases lacked significant inflammation, fatty change, biliary tract disease, vascular disease, nodular regenerative hyperplasia, iron overload, inherited metabolic or storage disorder, viral hepatitis, or fibrosis. Biopsies for follow-up of known liver diseases were excluded. Transplant biopsies, lesion-directed biopsies, biopsies obtained during bariatric surgery, liver donor biopsies, and biopsies to evaluate methotrexate toxicity were excluded. Clinical (including follow-up) and laboratory data were collected. The frequency of almost-normal liver biopsies was 0.6% and 3.7% at the 2 institutions. The most common biopsy indications were elevated liver biochemistries or clinical findings that suggested portal hypertension. In 70 patients (72%), an associated clinical abnormality was identified; the most common were autoimmune systemic inflammatory conditions (18%), vascular/ischemic events (13%), metabolic syndrome (11%), drug effects (8%), and inflammatory conditions of the gastrointestinal tract (7%). The median follow-up period was 4.3 years (range=0 to 10 y); detailed clinical follow-up was available for 66 patients (68%). Liver biochemistries normalized in 32 patients (48.5%) and remained elevated in 34 (51.5%). Seven patients (7.2%) eventually developed chronic liver disease (autoimmune hepatitis [n=3], primary biliary cirrhosis [n=3], cryptogenic cirrhosis [n=1]). This multicenter study determines the differential diagnosis for almost-normal liver biopsies; this will guide pathologists in subsequent workup efforts in these challenging cases.

A cluster of lead poisoning among consumers of Ayurvedic medicine.

BACKGROUND: Use of alternative medications and herbal remedies is widespread in the United States and across the globe. These traditional medications can be contaminated with toxic metals. Despite several case reports of poisoning from such contamination, the epidemiological data are still limited. OBJECTIVES: To report on a cluster of lead and mercury toxicity cases in 2011 among a community of adherents of traditional medical practice of Ayurveda. METHODS: Adherents of Ayurveda were offered heavy metals screening following the identification of the index case. RESULTS: Forty-six of 115 participants (40%) had elevated blood lead levels (BLLs) of 10 µg/dl or above, with 9.6% of BLLs at or above 50 µg/dl. CONCLUSIONS: This is the largest cluster of lead and mercury toxicity following use of Ayurvedic supplements described in the literature in the US. Contamination of herbal products is a public health issue of global significance. There are few regulations addressing contamination of "natural" products or supplements.

Agreement between fixed-ratio and lower limit of normal spirometry interpretation protocols decreases with age: is there a need for a new GOLD standard?

OBJECTIVES: To assess concordance between the fixed 70% ratio cutoff point with the fixed percent predicted values (Fixed-ratio) and the lower limit of normal (LLN) algorithms in interpreting spirometry results in an older population. METHODS: Spirometries were interpreted using Third National Health and Nutrition Examination Survey reference equations for 2319 workers. RESULTS: The Fixed-ratio algorithm characterized 34.5% (n = 801) results as abnormal, compared with 29.7% (n = 689) by the LLN. There were almost twice as many obstructive and mixed airways spirometries identified under the Fixed-ratio compared to LLN. Rates of restrictive pattern physiology were virtually the same under each algorithm. Overall agreement between the algorithms decreased with age from "almost perfect" for those younger than 60 years to "substantial" for those older than 80 years. CONCLUSIONS: This study found age-related discordance between two algorithms possibly related to the lack of reference equations and standards for individuals older than 80 years.