Departments of 1Radiology, 2Histopathology and 3Family Medicine, Royal Hospital, Muscat, Oman *Corresponding Author’s e-mail: alumairi1@yahoo.com حالة داء النشوائي العقيدي الرئوي مشاهبا للعقيدات الرئوية السرطانية تقرير حالة و استعراض األدبيات العلمية را�شد العمريي، فاطمة اللواتية، ف�شيلة حممد البو�شعيدية abstract: Amyloidosis is a disorder characterised by the extracellular deposition of amyloid, a fibrillary protein, in various organs such as the lungs. Pulmonary nodular amyloidosis can mimic other lung conditions that present with pulmonary nodules, such as metastasis, sarcoidosis and hyalinising granuloma. We report a 60-year-old man who presented to the Royal Hospital, Muscat, Oman, in 2017 with a history of shortness of breath upon exertion, orthopnoea and bilateral lower limb swelling. A chest X-ray showed bilateral nodular opacities. Enhanced chest computed tomography revealed bilateral pulmonary nodules with a predominantly perilymphatic and subpleural distribution, giving the impression of a neoplastic nodule. A histopathological examination of biopsied lung tissue confirmed a diagnosis of nodular pulmonary amyloidosis. Keywords: Multiple Pulmonary Nodules; Amyloidosis; Computed Tomography; Case Report; Oman. يف اخللية ج�شم خارج ليفي( بروتني )الأميلويد، الن�شا �شبيهة مادة برت�شب تت�شف مر�شية حالة هو )الأميلويد( الن�شواين داء امللخ�ص: اأع�شاء خمتلفة من ج�شم الأن�شان مبا يف ذلك الرئتني، داء الن�شواين العقيدي الرئوي قد ي�شابه اأمرا�شًا وحالت رئوية اأخرى تت�شف بظهور عقيدات رئوية، ومن هذه احلالت العقيدات ال�رسطانية اخلبيثة املنتقلة من ع�شو اآخر، وت�شخم ال�شاركويد والورم احلبيبي ال�شفاف، نعر�ص هنا حالة لرجل يبلغ من العمر 60 عامًا مت معاينته يف امل�شت�شفى ال�شلطاين يف م�شقط ب�شلطنة عمان يف عام 2017، وكان يعاين من �شيق يف التنف�ص عند بذل جمهود وعند ال�شطجاع وكذلك من انتفاخ يف القدمني، وقد اأظهرت ال�شعة ال�شينية لل�شدر وجود عقيدات يف كلتا الرئتني، ملعرفة املزيد عن طبيعة هذه العقيدات الرئوية مت اإجراء اإ�شعة مقطعية مع ا�شتخدام �شبغة عن طريق الوريد والتي او�شحت وجود عقيدات رئوية تتوزع ب�شكل ملحوظ يف حميط الأوعية اللمفاوية وحتت اجلنبة، اأعطت هذه العقيدات ا�شتباهًا باأنها متثل اأورامًا �رسطانية، اإل اأن الفح�ص املجهري الن�شيجي لعينة اأخذت من الرئة اأكدت ت�شخي�ص داء الن�شواين )الأميلويد( الرئوي العقيدي. الكلمات املفتاحية: عقيدات رئوية متعددة؛ داء الن�شواين )الأميلويد(؛ اأ�شعة مقطعية؛ تقرير حالة؛ عمان. Nodular Pulmonary Amyloidosis Mimicking Metastatic Pulmonary Nodules A case report and review of the literature *Rashid S. Al-Umairi,1 Fatma Al-Lawati,2 Fadhila M. Al-Busaidi3 Sultan Qaboos University Med J, August 2018, Vol. 18, Iss. 3, pp. e393–396, Epub. 19 Dec 18 Submitted 3 Feb 18 Revisions Req. 11 Feb & 27 Mar 18; Revisions Recd. 19 Feb & 14 Apr 18 Accepted 26 Apr 18 online case report doi: 10.18295/squmj.2018.18.03.023 Amyloidosis is a disorder resulting from the abnormal extracellular accumulation of amy-loid in various tissues and organs.1 Amyloidosis can be primary (i.e. idiopathic) or, more commonly, sec- ondary to a variety of pathological conditions, including neoplastic, infectious and inflammatory aetiologies.2–4 Pulmonary amyloidosis may be part of a systemic process or confined only to the lung, at which point it is classified as tracheobronchial, parenchymal nodular or diffuse alveolar septal pulmonary amyloidosis.5,6 Although rare, nodular pulmonary amyloidosis can mimic other, more common, pulmonary disorders that manifest as multiple pulmonary masses or nodules, such as neoplastic and granulomatous conditions.2,7,8 Therefore, pulmonary amy- loidosis should be included in the differential diagnosis of single or multiple pulmonary nodules. Case Report A 60-year-old man presented to the Emergency Depart- ment of the Royal Hospital, Muscat, Oman, in 2017 with a recent history of shortness of breath upon exertion, orthopnoea and bilateral lower limb swelling. He was an ex-smoker, diabetic and was currently taking insulin. There was no history of fever or chest pain, although he had dilated cardiomyopathy with a left ventricle ejection fraction of 35%. Upon physical examination, there were bilateral chest crepitations and bilateral lower limb oedema. All vital signs and other systemic examinations were unremarkable. A complete blood count, erythrocyte sedimentation rate, C-reactive protein level and renal and liver function tests were within normal limits. Nodular Pulmonary Amyloidosis Mimicking Metastatic Pulmonary Nodules A case report and review of the literature e394 | SQU Medical Journal, August 2018, Volume 18, Issue 3 The patient subsequently underwent a chest X-ray which showed bilateral nodular opacities [Figure 1]. Further evaluation using enhanced computed tomo- graphy (CT) revealed bilateral pulmonary nodules with a predominantly perilymphatic and subpleural distrib- ution. The largest nodule arose in the right upper lobe, abutting the fissure, and measured 2.3 × 2.9 cm. There was no evidence of pleural effusion or enlargement of the lymph nodes, although some of the nodules showed central calcification [Figure 2]. The preliminary diagnosis was of a neoplastic nodule that required further invest- igation. Accordingly, CT scans of the abdomen and pelvis were performed; however, the findings were unrem- arkable. A tissue biopsy from the lung nodules was obtained under CT guidance. A microscopic examination of the tissue sample showed cores of hyalinised tissue with foci of haemorrhage. A haematoxylin and eosin stain showed deposits of eosinophilic amorphous material [Figure 3]. A special stain with Congo red and thioflavin T dyes revealed deposition of amyloid fibrils, consistent with a histological diagnosis of amyloidosis. As the patient was asymptomatic and there were no features suggestive of systemic amyloidosis, the decision was made to keep the patient under regular follow-up and observation. Discussion Amyloidosis has an estimated global incidence of approx- imately 10 cases per million patients each year.9 To the best of the authors’ knowledge, the present case is the first to be reported from Oman. According to the site of deposition, amyloidosis can be categorised as systemic or localised. The four subtypes of systemic amyloidosis are primary light-chain amyloidosis, sec- ondary amyloid A amyloidosis, familial amyloidosis and β2-microglobulin-related amyloidosis.10 The most common is secondary amyloid A amyloidosis, resulting from deposited amyloid P component. It mainly occurs in patients with chronic infections and those with rheum- atic or autoimmune diseases.1,2 In contrast, primary light- chain amyloidosis is due to deposited kappa and lambda light chains and can be associated with multiple myeloma, Waldenström’s macroglobulinaemia and asymptomatic monoclonal gammopathy.1 Isolated pulmonary amyloidosis is rare and can be categorised into tracheobronchial, parenchymal nodular and diffuse alveolar septal amyloidosis.5,6 Hui et al. rep- orted 48 patients with localised respiratory amyloidosis, of which 14 had tracheobronchial amyloidosis, 28 showed either solitary or multiple pulmonary nodules and six had a diffuse interstitial parenchymal pattern.11 Most of the Figure 1: Chest X-ray of a 60-year-old man with shortness of breath upon exertion, orthopnoea and bilateral lower limb oedema showing several nodular opacities (arrows), predominantly in the right lung. Figure 3: Haematoxylin and eosin stain at x10 magnif- ication showing eosinophilic and amorphous material deposits (arrows). Figure 2: High-resolution chest computed tomography scans in the (A & B) axial and (C & D) coronal views of a 60-year-old man with shortness of breath upon exertion, orthopnoea and bilateral lower limb oedema showing bilateral pulmonary nodules (arrows) with central calcif- ication of the right upper nodule (arrowhead). Rashid S. Al-Umairi, Fatma Al-Lawati and Fadhila M. Al-Busaidi Online Case Report | e395 red staining, the amyloid proteins display green bire- fringence under polarised light.2,3,9,12 Due to the rarity of the condition, no randomised controlled trials have yet been conducted regarding nodular pulmonary amyloidosis management. However, the general consensus is that treatment depends on the severity of the symptoms. For example, for asympt- omatic patients, regular follow-up and careful monitoring may be sufficient.2 In contrast, different treatment options may be necessary for symptomatic patients, including conservative excision, carbon dioxide laser ablation and low-dose external beam radiation.9,18 Conclusion Nodular pulmonary amyloidosis is a rare and usually localised disease that can mimic other nodular pulmonary disorders, such as neoplastic and granulomatous pro- cesses. As such, this condition should be included in the differential diagnosis of pulmonary nodules or masses. References 1. Baker KR, Rice L. The amyloidoses: Clinical features, diagnosis and treatment. Methodist Debakey Cardiovasc J 2012; 8:3–7. 2. Lee SH, Ko YC, Jeong JP, Park CW, Seo SH, Kim JT, et al. Single nodular pulmonary amyloidosis: Case report. Tuberc Respir Dis (Seoul) 2015; 78:385–9. doi: 10.4046/trd.2015.78.4.385. 3. Sipe JD, Benson MD, Buxbaum JN, Ikeda S, Merlini G, Saraiva MJ, et al. Amyloid fibril protein nomenclature: 2012 recommendations from the Nomenclature Committee of the International Society of Amyloidosis. Amyloid 2012; 19:167–70. doi: 10.3109/13506 129.2012.734345. 4. Gernay C, Médart L. Multiple calcified nodules in pulmonary amyloidosis. JBR-BTR 2014; 97:370. doi: 10.5334/jbr-btr.133. 5. Czeyda-Pommersheim F, Hwang M, Chen SS, Strollo D, Fuhrman C, Bhalla S. Amyloidosis: Modern cross-sectional imaging. Radiographics 2015; 35:1381–92. doi: 10.1148/rg.201 5140179. 6. Utz JP, Swensen SJ, Gertz MA. Pulmonary amyloidosis. The Mayo Clinic experience from 1980 to 1993. Ann Intern Med 1996; 124:407–13. doi: 10.7326/0003-4819-124-4-199602150- 00004. 7. Gaurav K, Panda M. An uncommon cause of bilateral pulm- onary nodules in a long-term smoker. J Gen Intern Med. 2007; 22:1617–20. doi: 10.1007/s11606-007-0324-z. 8. Morisaki K, Shoji F, Kawano D, Yano T, Maehara Y. [Primary nodular pulmonary amyloidosis]. Kyobu Geka 2009; 62:1006–9. 9. Milani P, Basset M, Russo F, Foli A, Palladini G, Merlini G. The lung in amyloidosis. Eur Resp Rev 2017; 26:1740046. doi: 10.1183/16000617.0046-2017. 10. Real de Asúa D, Costa R, Galván JM, Filigheddu MT, Trujillo D, Cadiñanos J. Systemic AA amyloidosis: Epidemiology, diagnosis, and management. Clin Epidemiol 2014; 6:369–77. doi: 10.2147/ CLEP.S39981. 11. Hui AN, Koss MN, Hochholzer L, Wehunt WD. Amyloidosis presenting in the lower respiratory tract: Clinicopathologic, radiologic, immunohistochemical, and histochemical studies on 48 cases. Arch Pathol Lab Med 1986; 110:212–18. patients with nodular amyloidosis were asymptomatic, while those with tracheobronchial or diffuse interstitial amyloidosis had respiratory symptoms.11 In a 13-year study of 55 patients with biopsy-proven pulmonary amyloidosis, Utz et al. reported that 35 had primary systemic amyloidosis, 17 had amyloidosis localised to the respiratory system and three had secondary or familial amyloidosis.6 Of the patients with localised amyloidosis, seven had nodular amyloidosis and four had tracheobronchial amyloidosis. Nodular amyloidosis was not associated with systemic amyloidosis and had a predominantly benign prognosis.6 Tracheobronchial amyloidosis usually presents with symptoms related to airway obstruction such as dysp- noea, coughing, recurrent pneumonia and haemoptysis.7,9 The classic radiological features of tracheobronchial amyloidosis are tracheal lumen irregularities, bronchial wall thickening and calcified amyloid deposition, which can be mural or endobronchial, resulting in subseg- mental collapse.5,7,12 Diffuse interstitial parenchymal amyloidosis is the rarest type of pulmonary amylo- idosis and usually occurs among patients with systemic amyloidosis.9 The deposited amyloid results in alveolar wall and capillary damage, leading to impaired gas exchange. As with tracheobronchial amyloidosis, patients usually present with a cough, dyspnoea and haemop- tysis, or a combination of these symptoms. Classic radiol- ogical findings include non-specific interstitial and alv- eolar opacities, predominantly basal and peripheral, well- defined nodules and confluent subpleural opacities.5,13 Nodular amyloidosis is usually localised to the respiratory system.6 Affected patients are generally asymptomatic and the amyloid nodules detected incid- entally.14 On CT imaging, nodular amyloidosis can present as multiple lesions or, less commonly, as a single lesion with lower lobe and subpleural predom- inance.14–16 The amyloid nodules are usually well- defined with lobulated contours; they can vary in size from 0.5–15 cm and may gradually grow over time without regression. Approximately half of all amyloid nodules calcify, although they rarely cavitate.14,15 In the current case, the patient had localised amyloidosis with no evidence of systemic involvement. A chest CT scan showed bilateral pulmonary nodules with a peri- lymphatic and subpleural predilection and occasional central calcification. Nodular pulmonary amyloidosis can mimic other nodular pulmonary disorders, such as neoplastic and granulomatous processes.7,8,17 Therefore, a biopsy is required for diagnosis and to differentiate it from other nodular pulmonary disorders. 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J Bras Pneumol 2008; 34:528–31. doi: 10.1590/S1806-37132008000700013. 13. Graham CM, Stern EJ, Finkbeiner WE, Webb WR. High-reso- lution CT appearance of diffuse alveolar septal amyloidosis. AJR Am J Roentgenol 1992; 158:265–7. doi: 10.2214/ajr.158.2. 1729778. 14. Suzuki H, Matsui K, Hirashima T, Kobayashi M, Sasada S, Okamato N, et al. Three cases of the nodular pulmonary amyloidosis with a longterm observation. Intern Med 2006; 45:283–6. doi: 10.2169/internalmedicine.45.1487. 15. Vieira IG, Marchiori E, Zanetti G, Cabral RF, Takayassu TC, Spilberg G, et al. Pulmonary amyloidosis with calcified nodules and masses: A six-year computed tomography follow-up - A case report. Cases J 2009; 2:6540. doi: 10.4076/1757-1626-2- 6540. 16. Feng J, Li J, Ling C, Liu Q. A rare case of multinodular pul- monary amyloidosis. Clin Respir J 2016; 10:389–92. doi: 10.11 11/crj.12220. 17. Shin B, Ko J, Lee SS, Lim KS, Han JH, Chung MP, et al. 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