Large Thoracic Lymphadenopathy and Pulmonary Nodules in Young Man
Maros Rudnay, MD, PhD; Alzbeta Blichárová, MD, PhD; Michal Krupka, PhD; Ivana Paranicová, MD, PhD;
Pavol Pobeha, MD, PhD; Gabriela Rjasková, MD; and Viera Lehotská, Prof MD, PhD
CASE PRESENTATION: A 33-year-old man with obesity, systemic arterial hypertension, and psoriasis who had been treated previously with little success by a pulmonologist for chronic unproductive irritant cough came to the outpatient pulmonary department because of profuse cough and short syncope (probably cough-induced). Chest radiography revealed widened mediastinum with lobular, polycyclic contours that was suspected to be a large mediastinal lymphadenopathy or mediastinal mass. CHEST 2022; 161(3):e169-e173
Chest radigraph (only posteroanterior view was performed) is presented inFigure 1. Overall physical examination was normal; lung auscultation revealed only minimal, inconstant wheezing. Blood oxygen saturation was normal at 96%. According to the patient, spirometric examination recently performed by private practice pulmonologist was normal. ECG was normal, as was BP and body temperature. Because of syncope and tachycardia and mild D-dimer elevation, CT pulmonary angiography was performed to rule out pulmonary embolism. However, two notable pathologicfindings were discovered on scans. Large mediastinal and hilar lymphadenopathy was present (Fig 2); lymph nodes were enlarged, with pathologic round shape, with smooth edges and no calcifications. There were multiple confluent, tumor-like lymph nodes with lobulated contour, particularly in the right paratracheal region (Fig 3). Contrast enhancement of nodes was slightly inhomogeneous with several discrete hypointensities in structure. Neither the pulmonary trunk nor the pulmonary arteries were dilated; pulmonary
hypertension was not suggested. Other pathologic findings consisted of multiple pulmonary nodules that
Figure 1–Chest radiograph in posteroanterior view. There is widened mediastinum with lobular, polycyclic contour on the right side. L¼left.
AFFILIATIONS: From the Department of Radiology and Medical Im- aging (M. Rudnay and G. Rjasková), L. Pasteur University Hospital, Kosice, Slovakia; the II. Department of Radiology (M. Rudnay and V.
Lehotská), Faculty of Medicine of Comenius University in Bratislava and St. Elizabeth's Cancer Institute, Bratislava, Slovakia; the Depart- ment of Pathology (A. Blichárová), Pavol JozefSafárik University, Faculty of Medicine and L. Pasteur University Hospital, Kosice, Slovakia; the Department of Immunology (M. Krupka), Faculty of Medicine and Dentistry, Palacký University Olomouc, Czech Republic;
and the Department of Pneumology and Phtiseology (I. Paranicová
and P. Pobeha), Pavol JozefSafárik University, Faculty of Medicine and L. Pasteur University Hospital, Kosice, Slovakia.
FUNDING/SUPPORT:This work was supported by Palacký University grant IGA_LF_2021_015.
CORRESPONDENCE TO:Maros Rudnay, MD, PhD; email:maros.rud- [email protected]
CopyrightÓ2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.
DOI:https://doi.org/10.1016/j.chest.2021.10.008
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Chest Imaging and Pathology for Clinicians]
varied in size from 2 to 13 mm. Nodules had irregular borders; most were solid, and few had a solid appearance with a very discrete ground-glass halo around the solid part (Fig 4). The largest nodules showed inhomogeneous contrast enhancement. Nodules had random
distribution and strong basal predominance. Given the radiologic image, mediastinal lymphadenopathy and randomly distributed pulmonary nodules with basal predominance, two potential diagnoses (lymphoma with pulmonary involvement and systemic dissemination of malignant disease), were suggested by the radiologist.
Most of the hematologic and biochemical laboratory parameters (including oncomarkers) were in the physiologic range. Only minimal signs of inflammation, mild elevation of WBCs with monocytosis, and elevated C-reactive protein levels were present. Other types of WBCs were not elevated significantly. There was no elevation in overall immunoglobulin level or in
individual classes of immunoglobulins.Endobronchially, hyperemic bronchial mucosa was covered by small nodular granulations of the mucosal surface.
Endobronchial sonography was not performed because it is not available in the hospital.
Cytologic evaluation of BAL and histologic evaluation of microexcisions discovered no malignant cells. There were extensive chronic inflammatory infiltration changes and epithelioid nodules in the lamina propria mucosae.
Figure 2–Massive mediastinal and hilar lymphadenopathy on initial contrast-enhanced CT scan in mediastinal window (yellow arrowhead).
Figure 3–Multiple confluent, tumor-like lymph node packets, partic- ularly in the right paratracheal region on CT scan: coronal plane, mediastinal window (yellow arrows).
Figure 4–Nodules with irregular borders seen on CT scan. Some are solid; few have a discrete ground-glass halo around the solid part: pul- monary window in multiple regions (red arrows).
Figure 5–Noncaseous granulomatous reaction destroyed and replaced the normal structure of the lymph node. Big multinuclear cells (black arrowheads), which are typical for granulomatous reaction around the foreign body, are visible at multiple points in the pathologic infiltrate:
high-power micrograph, hematoxylin-eosin stain, 200x.
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Because there was no conclusive answer for the cause of the process, video-assisted thoracoscopy was performed with mediastinal lymph node biopsy and small lung
resection of a few pulmonary nodules. Histologic examination of the lung sample revealed granulomata around foreign bodies: oval-shaped structures with thick wallfilled with eosinophilic granules in pulmonary nodules and noncaseous granulomatous lymphadenitis in mediastinal lymph nodes (Figs 5-7).
What is the diagnosis?
Figure 6–The underlying pathologic structure in the nodules is visible as an oval structure that contains eosinophilic granules with thick walls surrounded by the granulomatous reaction: high-power micrograph, hematoxylin-eosin stain, 400x.
Figure 7–Another similar structure is visible on another micrograph in the lumen of the bronchiole (black arrow): high-power micrograph, hematoxylin-eosin stain, 400x.
Diagnosis: Ascariasis: granulomatous in fl ammatory reaction around Ascaris lumbricoides eggs in pulmonary tissue and noncaseous granulomatous lymphadenitis in mediastinal lymph nodes
Discussion
Clinical Discussion
This case demonstrates a unique and hitherto unseen finding ofAscaris lumbricoideseggs localized in the pulmonary parenchyma. The life cycle ofAscaris lumbricoidesis very particular. The way of infection is via the oral-fecal route, by ingestion of infective egg. Eggs hatch in the intestinal tract, and hatched larvae pierce the bowel mucosa and migrate through the portal venous system and liver to the lung. They penetrate alveolar membranes and move to the laryngopharyngeal junction;
larvae are ingested and travel into the small intestine where they reach sexual maturity and start producing eggs. Eggs are excreted by feces to the environment without any migration to any other tissues.1,2
Repeated stool analyses of the patient were negative for eggs. We presume that, at the time of diagnosis, there were no viable worms present in the GI tract; the only presence of the parasite in the organism were eggs disseminated in the lungs. Furthermore, the patient had no symptoms of active intestinal infection, and his dominant subjective complaint was a cough, probably because of an allergic reaction to Ascaris eggs or because of the enlarged mediastinal lymph nodes irritating the bronchi and chronic inflammation in bronchial mucosa (similarly as in, eg, sarcoidosis).3,4 Laboratoryfindings implied the presence of an inflammatory response.
However, the absence of the elevated eosinophil count and IgE antibodies did not indicate parasitic infection.
Imaging Discussion
Chest radiography (Fig 1), which is the most basic examination and, in most cases, thefirst radiologic examination of a patient with chest complaints, was already suggestive for extensive disease. The most prominent pathologicfinding was the mediastinal widening; the width of upper mediastinum (portion of mediastinal shadow above the hila) was exceeding 6 to 8 cm.5The right side of the enlarged shadow has polycyclic or lobulated contour, which is a feature that suggested that underlying cause can be a lobulated solid mass or multiple enlarged lymph nodes in the
mediastinum. The other main pathologicfinding
(pulmonary nodules) was detected only by CT examination, because the nodules were too small to be detected by radiography. From a radiologic point of view, the combination of mediastinal lymphadenopathy and pulmonary nodules hinted at multiple different diseases.
Mediastinal lymphadenopathy of this extent occurs mainly in lymphoproliferative diseases or other neoplastic processes, even of extrathoracic origin.
Additionally, mediastinal lymphadenopathy is a common manifestation of granulomatous diseases of the lung, most typically sarcoidosis. However, nodules are small (miliary) in sarcoidosis, with perilymphatic distribution and upper lobes predominance.6In our case, the distribution and CT morphologic evidence of the pulmonary nodules favored neoplastic dissemination; the variable size of nodules, the postcontrast enhancement of the largest nodules, and the basal predominance of the distribution that is typical for hematogenous
dissemination of pulmonary metastases.
Pathologic Discussion
Pathologic and immunologic point of view was decisive in this case. The noncaseous granulomatous reaction destroyed and replaced the normal structure of the lymph node (Fig 5). Big multinuclear cells, which are typical for granulomatous reaction around the foreign body, are visible at multiple points in the pathologic infiltrate. A definitive answer, however, was provided by examination of pulmonary nodules. The sample consisted of a wedge- shaped lung section of the lung that contained multiple firm nodules with a size of approximately 4 mm. The underlying pathologic structure in the nodules is visible on a high-power micrograph (Fig 6): oval structure containing eosinophilic granules with thick walls surrounded by the granulomatous reaction. Another similar structure is visible on another micrograph (Fig 7) of the lumen of the bronchiole. The structure corresponds to an image of Ascaris lumbricoidesegg in infertile/undeveloped stage:
thinner wall with proteinaceous granules inside, without the image of embryonal stages or viable larva inside.7 Granuloma formation occurs in various parasitic infections that are caused by both protozoa and worms, but not typically in association with the presence of larval and adult stages ofAscaris.8Migrating larval stages ofAscaris in the lungs can trigger an immune response that is characterized by eosinophil infiltration (Löffler syndrome), but that was not observed in this case. Thus, mainly the nonspecific recognition ofAscaris eggs as foreign bodies is probably involved in the formation of granulomas.
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Given the histologic specimen, where the egg seemed to be located inside the terminal bronchiole, we supposed bronchogenic spread of eggs, most probably by aspiration; however, because of the rarity of the case, the exact mechanism is unknown. We can only speculate about this, because the CT image suggests otherwise; the distribution and image of nodules are more typical for the hematogenous spread of disease.
We did notfind other cases of pulmonary dissemination ofAscariseggs in humans, but we found few similar case reports; Mello et al9describe granulomatous peritonitis in a child in a case in which the worm, through perforation of the intestine, deposed eggs freely in the peritoneal cavity, which provoked an intense
granulomatous inflammatory reaction. Three cases with similarfindings were reported by Walter and
Krishnaswami10in 1989, where thefinding during surgery was supposed to be TB; however, as in our case, the correct diagnosis was made only after histologic examination of tissues.9,10This publication is probably thefirst to show that not only larvae but also eggs of Ascaris lumbricoidescan migrate to the lungs.
Conclusions
Ascariasis can be a rare cause of granulomatous in- flammatory reaction, even outside the abdominal cavity.
Ascariseggs can disseminate outside the GI tract, even into the lungs, and radiologically mimic a neoplastic process.
Radiologic and clinical imaging is not specific;final diagnosis can be made only by direct histologic examination.
Acknowledgments
Financial/nonfinancial disclosures:None declared.
Role of sponsors:The sponsor had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript.
Other contributions:CHESTworked with the authors to ensure that the Journal policies on patient consent to report information were met.
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