No abstract

Coccidioides immitis/Coccidioides posadasii are common causes of pulmonary infection in certain geographic areas, and are highly infectious when working with culture isolates in the laboratory. Rapid techniques to accurately identify this pathogen in tissues may be of benefit for diagnosis and in limiting the exposure of laboratory personnel to this agent. Locked nucleic acids (LNA) are modified nucleotides in which a ribonucleoside is linked between the 2'-oxygen and the 4'-carbon atoms with a methylene unit. LNA oligonucleotides exhibit increased thermal stability and make excellent probes for in situ hybridization (ISH). In this study, ISH utilizing a biotin-labeled LNA probe targeting Coccidioides sp. ribosomal RNA sequences in 6 formalin-fixed, paraffin-embedded pulmonary tissue specimens from 6 patients with culture positive or histologic findings suggestive of Coccidioides sp. infection is described. The cultures of the pulmonary specimens confirmed C. immitis in 3 of 6 patients. The ISH procedure with the LNA probe was positive in all 6 cases, although the number of organisms that were highlighted varied from rare to numerous. ISH with a biotin-labeled DNA probe of the same sequence was positive in 4 of the 6 cases and the signal intensity and number of organisms was much less than that observed with the LNA probe. Negative control tissues containing a variety of different fungal pathogens including Aspergillus sp., Fusarium sp., Blastomyces dermatitidis, Candida sp, Histoplasma capsulatum, and Zygomyces did not hybridize with the LNA and DNA probes. ISH with an LNA oligonucleotide probe targeting Coccidioides sp. ribosomal RNA is useful for rapid ISH. ISH could be rapidly performed when fungal pathogens are observed in tissue but cultures are negative or have not been performed.

A 33-year-old female collapsed and died suddenly after presenting with acute dyspnea and increasing cough over the preceding several months. Autopsy revealed poorly differentiated linitis plastica adenocarcinoma of the stomach. Microscopic examination of the lungs showed features consistent with pulmonary tumor thrombotic microangiopathy (PTTM). PTTM is a well-described complication in patients with adenocarcinoma. The typical presentation involves acute pulmonary hypertension, right-sided heart failure, and sudden death, often before the adenocarcinoma is discovered. The pathophysiology of PTTM remains elusive; it has been suggested that carcinoma cells may produce substances that influence pulmonary vasculature. Our patient had classic clinical and histologic features of PTTM in addition to prominent extravascular compression by intralymphatic tumor cells. These features undoubtedly caused her precipitous decline and lethal pulmonary hypertension, induced by underlying adenocarcinoma. This case demonstrates that sudden death can occur from pulmonary hypertension induced by metastatic carcinoma with remarkably little prior symptomatology.