Vol 61, No 2 (2023)
Review paper
Published online: 2023-07-06

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Rare benign lung tumours presenting with high clinical suspicion for malignancy: a case series and review of the literature

Katarina Popovic1, Mirjana Miladinović12, Ljiljana Vučković12, Mirjana Nedović Vuković3
Pubmed: 37435900
Folia Histochem Cytobiol 2023;61(2):130-142.

Abstract

Introduction. Incidentally discovered lung nodules can be worrisome for both the patient and their physicians. Although 95% of solitary lung nodules are benign, it is important to distinguish which nodules have high clinical suspicion for malignancy. Existing clinical guidelines do not apply to patients with signs and symptoms related to the lesion and with an increased baseline risk of lung cancer or metastasis. This paper highlights the vital role of pathohistological analysis and immunohistochemistry in the definitive diagnosis of such incidentally discovered lung nodules.

Material and methods. The three cases presented were selected based on their similar clinical presentations. A review of the literature was performed using the online database PubMed, for articles published in the period between January of 1973 to February of 2023 using the following medical subject headlines: “primary alveolar adenoma,” “alveolar adenoma,” “primary pulmonary meningioma,” “pulmonary meningioma,” and “pulmonary benign metastasizing leiomyoma.”

Results (Case Series). The case series consists of three incidentally discovered lung nodule(s). Although they presented with high clinical suspicion for malignancy, detailed workup confirmed the diagnosis of three rare benign lung tumours: primary alveolar adenoma, primary pulmonary meningioma, and benign metastasizing leiomyoma.

Conclusions. Clinical suspicion for malignancy in the presented cases arose from previous and current medical history of malignancy, family history of malignancy, and/or specific radiographic findings. This paper highlights the need for a multidisciplinary approach in the management of incidentally discovered pulmonary nodules. Excisional biopsy and pathohistological analysis remain the gold standard in confirming the presence of a pathologic process and determining the nature of the disease. Common features of the diagnostic algorithm utilized among the three cases include multi-slice computerized tomography, excisional biopsy via atypical wedge resection (if the nodule is peripherally located), and lastly, pathomorphological analysis using haematoxylin and eosin staining and immunohistochemistry.

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References

  1. Weinberger SE, McDermott S. Diagnostic evaluation of the incidental pulmonary nodule. UpToDate. https://www.uptodate.com/contents/diagnostic-evaluation-of-the-incidental-pulmonary-nodule#subscribeMessage (21.03.2023).
  2. Hansell DM, Bankier AA, MacMahon H, et al. Fleischner Society: glossary of terms for thoracic imaging. Radiology. 2008; 246(3): 697–722.
  3. Callister MEJ, Baldwin DR, Akram AR, et al. et al.. BTS Guidelines for Investigation and Management of Pulmonary Nodules. Thorax. 2015; 70(2): ii7.
  4. Albert RH, Russell JJ. Evaluation of the solitary pulmonary nodule. Am Fam Physician. 2009; 80(8): 827–831.
  5. Jamil A, Kasi A. Lung Metastasis. StatPearls [Internet], Treasure Island .
  6. Bhavsar T, Uppal G, Travaline JM, et al. An unusual case of a microscopic alveolar adenoma coexisting with lung carcinoma: a case report and review of the literature. J Med Case Rep. 2011; 5: 187.
  7. Yousem SA, Hochholzer L. Alveolar adenoma. Hum Pathol. 1986; 17(10): 1066–1071.
  8. Lu YW, Chang SL, Yeh YC, et al. Alveolar adenoma and coexisting atypical adenomatous hyperplasia: a case report and literature review. Pathologica. 2022; 114(4): 326–331.
  9. Burke LM, Rush WI, Khoor A, et al. Alveolar adenoma: a histochemical, immunohistochemical, and ultrastructural analysis of 17 cases. Hum Pathol. 1999; 30(2): 158–167.
  10. Nosotti M, Mendogni P, Rosso L, et al. Alveolar adenoma of the lung: unusual diagnosis of a lesion positive on PET scan. A case report. J Cardiothorac Surg. 2012; 7: 1.
  11. González ET, Sánchez-Yuste R, Jiménez-Heffernan JA. Cytologic features of pulmonary alveolar adenoma. Acta Cytol. 2008; 52(6): 739–740.
  12. Tang X, Wu Z, Shen Y. Coexistence of lung alveolar adenoma with cerebral arteriovenous malformations: A case report and literature review. Oncol Lett. 2015; 10(1): 250–254.
  13. Sak SD, Koseoglu R, Demirag F, et al. Alveolar adenoma of the lung. APMIS. 2007; 115(12): 1443–1449.
  14. Gan M, Weng S, Zheng H, et al. Coexistence of lung alveolar adenoma with bronchogenic cyst: a case report and literature review. Int J Clin Exp Pathol. 2017; 10(1): 747–749.
  15. Kondo N, Torii I, Hashimoto M, et al. Alveolar adenoma of the lung: a case report. Ann Thorac Cardiovasc Surg. 2011; 17(1): 71–73.
  16. Okada S, Ohbayashi C, Nishimura M, et al. Malignant transformation of alveolar adenoma to papillary adenocarcinoma: a case report. J Thorac Dis. 2016; 8(5): E358–E361.
  17. Zhang X, Bai Y, Wang X. Ke Huang. Alveolar adenoma with the round-shaped mesenchymal cells: a rare case and review of literature. Int J Clin Exp Pathol. 2017; 10(2): 3936–3939.
  18. Semeraro D, Gibbs AR. Pulmonary adenoma: a variant of sclerosing haemangioma of lung? J Clin Pathol. 1989; 42(11): 1222–1223.
  19. Halldorsson A, Dissanaike S, Kaye KS. Alveolar adenoma of the lung: a clinicopathological description of a case of this very unusual tumour. J Clin Pathol. 2005; 58(11): 1211–1214.
  20. Wu RI. Sclerosing pneumocytoma. https://www.pathologyoutlines.com/topic/lungtumorsclerosingheman.html (22.03.2023).
  21. Galambos C, Nodit L. Identification of lymphatic endothelium in pediatric vascular tumors and malformations. Pediatr Dev Pathol. 2005; 8(2): 181–189.
  22. Burgdorf WH, Mukai K, Rosai J. Immunohistochemical identification of factor VIII-related antigen in endothelial cells of cutaneous lesions of alleged vascular nature. Am J Clin Pathol. 1981; 75(2): 167–171.
  23. Inamura K. Clinicopathological characteristics and mutations driving development of early lung adenocarcinoma: tumor initiation and progression. Int J Mol Sci. 2018; 19(4).
  24. Travis WD, Asamura H, Bankier AA, et al. International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee and Advisory Board Members. The IASLC lung cancer staging project: proposals for coding T categories for subsolid nodules and assessment of tumor size in part-solid tumors in the forthcoming eighth edition of the TNM classification of lung cancer. J Thorac Oncol. 2016; 11(8): 1204–1223.
  25. Huang S, Chen Li, Mao Y, et al. Primary pulmonary meningioma: A case report. Medicine (Baltimore). 2017; 96(19): e6474.
  26. Fujikawa R, Arai Y, Otsuki Y, et al. A case of a primary pulmonary meningioma mimicking a metastasis from a papillary thyroid carcinoma due to a size reduction after radioactive iodine therapy. Surg Case Rep. 2020; 6(1): 57.
  27. Incarbone M, Ceresoli GL, Di Tommaso L, et al. Primary pulmonary meningioma: report of a case and review of the literature. Lung Cancer. 2008; 62(3): 401–407.
  28. Zhang DB, Chen T. Primary pulmonary meningioma: A case report and review of the literature. World J Clin Cases. 2022; 10(13): 4196–4206.
  29. Kemnitz P, Spormann H, Heinrich P. Meningioma of lung: first report with light and electron microscopic findings. Ultrastruct Pathol. 1982; 3(4): 359–365.
  30. Weber C, Pautex S, Zulian GB, et al. Primary pulmonary malignant meningioma with lymph node and liver metastasis in a centenary woman, an autopsy case. Virchows Arch. 2013; 462(4): 481–485.
  31. Kim YY, Hong YK, Kie JH, et al. Primary pulmonary meningioma: an unusual cause of a nodule with strong and homogeneous enhancement. Clin Imaging. 2016; 40(1): 170–173.
  32. Prayson RA, Farver CF. Primary pulmonary malignant meningioma. Am J Surg Pathol. 1999; 23(6): 722–726.
  33. van der Meij JJC, Boomars KA, van den Bosch JMM, et al. Primary pulmonary malignant meningioma. Ann Thorac Surg. 2005; 80(4): 1523–1525.
  34. Žulpaitė R, Jagelavičius Ž, Mickys U, et al. Primary pulmonary meningioma with rhabdoid features. Int J Surg Pathol. 2019; 27(4): 457–463.
  35. Travis W, Brambilla E, Nicholson A, et al. The 2015 World Health Organization Classification of Lung Tumors. J Thorac Oncol. 2015; 10(9): 1243–1260.
  36. Juan CM, Chen ML, Ho SY, et al. Primary Pulmonary Meningioma Simulating a Pulmonary Metastasis. Case Rep Pulmonol. 2016; 2016: 8248749.
  37. de Perrot M, Kurt AM, Robert J, et al. Primary pulmonary meningioma presenting as lung metastasis. Scand Cardiovasc J. 1999; 33(2): 121–123.
  38. Cura M, Smoak W, Dala R. Pulmonary meningioma: false-positive positron emission tomography for malignant pulmonary nodules. Clin Nucl Med. 2002; 27(10): 701–704.
  39. Meirelles GS, Ravizzini G, Moreira AL, et al. Primary pulmonary meningioma manifesting as a solitary pulmonary nodule with a false-positive PET scan. J Thorac Imaging. 2006; 21(3): 225–227.
  40. Cimini A, Ricci F, Pugliese L, et al. A patient with a benign and a malignant primary pulmonary meningioma: an evaluation with 18F fluorodeoxyglucose positron emission tomography/computed tomography and computed tomography with iodinated contrast. Indian J Nucl Med. 2019; 34(1): 45–47.
  41. Luo JZ, Zhan C, Ni X, et al. Primary pulmonary meningioma mimicking lung metastatic tumor: a case report. J Cardiothorac Surg. 2018; 13(1): 99.
  42. Perry A, Brat DJ. Practical surgical neuropathology: a diagnostic approach. Churchill Livingstone 2010.
  43. Gürçay N, Öztürk A, Demirağ F, et al. Primary pulmonary meningioma mimicking pulmonary metastasis: A rare case report. Turk Gogus Kalp Damar Cerrahisi Derg. 2020; 28(4): 699–701.
  44. Qiao JH. Minute pulmonary meningothelial-like nodules. https://www.pathologyoutlines.com/topic/lungtumormpmn.html (22.03.2023).
  45. Abdellatif E, Kamel D, Mandilla JG. Schwannoma. Minute pulmonary meningothelial-like nodules. https://www.pathologyoutlines.com/topic/softtissueschwannoma.html (4.01.2022).
  46. Jeong JH, Pyo JS, Kim NY, et al. Diagnostic roles of immunohistochemistry in thymic tumors: differentiation between thymic carcinoma and thymoma. Diagnostics (Basel). 2020; 10(7).
  47. Collini P, Negri T, Barisella M, et al. High-grade sarcomatous overgrowth in solitary fibrous tumors: a clinicopathologic study of 10 cases. Am J Surg Pathol. 2012; 36(8): 1202–1215.
  48. Doyle LA, Vivero M, Fletcher CDm, et al. Nuclear expression of STAT6 distinguishes solitary fibrous tumor from histologic mimics. Mod Pathol. 2014; 27(3): 390–395.
  49. Middleton LP, Duray PH, Merino MJ. The histological spectrum of hemangiopericytoma: application of immunohistochemical analysis including proliferative markers to facilitate diagnosis and predict prognosis. Hum Pathol. 1998; 29(6): 636–640.
  50. Barjon K. Uterine leiomyomata. StatPearls [Internet], Treasure Island 2020.
  51. Robboy SJ, Bentley RC, Butnor K, et al. Pathology and pathophysiology of uterine smooth-muscle tumors. Environ Health Perspect. 2000; 108 Suppl 5: 779–784.
  52. Rivera JA, Christopoulos S, Small D, et al. Hormonal manipulation of benign metastasizing leiomyomas: report of two cases and review of the literature. J Clin Endocrinol Metab. 2004; 89(7): 3183–3188.
  53. Chen S, Liu RM, Li T. Pulmonary benign metastasizing leiomyoma: a case report and literature review. J Thorac Dis. 2014; 6(6): E92–E98.
  54. Li Y, Xu T, Wang M, et al. Concurrent benign metastasizing leiomyoma in the abdominal wall and pelvic cavity: a case report and review of the literature. Front Surg. 2022; 9: 842707.
  55. Steiner PE. Metastasizing fibroleiomyoma of the uterus: Report of a case and review of the literature. Am J Pathol. 1939; 15(1): 89–110.7.
  56. Kayser K, Zink S, Schneider T, et al. Benign metastasizing leiomyoma of the uterus: documentation of clinical, immunohistochemical and lectin-histochemical data of ten cases. Virchows Arch. 2000; 437(3): 284–292.
  57. Efared B, Atsame-Ebang G, Sani R, et al. Unexpected pulmonary tumor: metastasis from a benign uterine leiomyoma in a post-menopausal woman: a case report. BMC Res Notes. 2017; 10(1): 662.
  58. Silva I, Tomé V, Oliveira J. Benign metastasising leiomyoma: a progressive disease despite chemical and surgical castration. BMJ Case Rep. 2012; 2012.
  59. Radzikowska E, Szczepulska-Wójcik E, Langfort R, et al. Benign pulmonary metastasizing leiomyoma uteri. Case report and review of literature. Advances in Respiratory Medicine. 2012; 80(6): 560–564.
  60. Hur JW, Lee S, Lee JB, et al. What are MRI findings of spine benign metastasizing leiomyoma? Case report with literature review. Eur Spine J. 2015; 24 Suppl 4: S600–S605.
  61. Yuan X, Sun Y, Jin Y, et al. Multiple organ benign metastasizing leiomyoma: A case report and literature review. J Obstet Gynaecol Res. 2019; 45(10): 2132–2136.
  62. Barnaś E, Książek M, Raś R, et al. Benign metastasizing leiomyoma: A review of current literature in respect to the time and type of previous gynecological surgery. PLoS One. 2017; 12(4): e0175875.
  63. Erlandson R. Diagnostic transmission electron microscopy of human tumors. The American Journal of Surgical Pathology. 1982; 6(5): 483.
  64. Uyama T, Monden Y, Harada K, et al. Pulmonary leiomyomatosis showing endobronchial extension and giant cyst formation. Chest. 1988; 94(3): 644–646.
  65. Lipton JH, Fong TC, Burgess KR. Miliary pattern as presentation of leiomyomatosis of the lung. Chest. 1987; 91(5): 781–782.
  66. Osadchy A, Zehavi T, Zissin R. Pulmonary benign metastasising leiomyomas presenting as fluid-containing masses on CT in a patient with two unrelated malignancies. Br J Radiol. 2005; 78(931): 639–641.
  67. Drevelengas A, Kalaitzoglou I, Sichletidis L. Benign pulmonary leiomyomatosis with cyst formation and breast metastasis: case report and literature review. Eur J Radiol. 1995; 19(2): 121–123.
  68. Ki EY, Hwang SJ, Lee KHo, et al. Benign metastasizing leiomyoma of the lung. World J Surg Oncol. 2013; 11: 279.
  69. Bakkensen JB, Samore W, Bortoletto P, et al. Pelvic and pulmonary benign metastasizing leiomyoma: A case report. Case Rep Womens Health. 2018; 18: e00061.
  70. Aka N, Iscan R, Köse G, et al. Benign pulmonary metastasizing leiomyoma of the uterus. J Clin Diagn Res. 2016; 10(9): QD01–QD03.
  71. Lee SaRa, Choi YI, Lee SJ, et al. Multiple cavitating pulmonary nodules: rare manifestation of benign metastatic leiomyoma. J Thorac Dis. 2017; 9(1): E1–E5.
  72. Pastré J, Juvin K, Grand B, et al. Pulmonary benign metastasizing leiomyoma presented as acute respiratory distress. Respirol Case Rep. 2017; 5(2): e00216.
  73. Wojtyś ME, Kacalska-Janssen O, Ptaszyński K, et al. Benign metastasizing leiomyoma of the lung: diagnostic process and treatment based on three case reports and a review of the literature. Biomedicines. 2022; 10(10).
  74. Alzeer A, Wu RI. Benign metastasizing leiomyoma. https://www.pathologyoutlines.com/topic/lungtumorb9metastasizingleio.html (9.01.2023).
  75. Kim YN, Eoh KJ, Lee JY, et al. Aberrant uterine leiomyomas with extrauterine manifestation: intravenous leiomyomatosis and benign metastasizing leiomyomas. Obstet Gynecol Sci. 2018; 61(4): 509–519.
  76. Mahmoud MS, Desai K, Nezhat FR. Leiomyomas beyond the uterus; benign metastasizing leiomyomatosis with paraaortic metastasizing endometriosis and intravenous leiomyomatosis: a case series and review of the literature. Arch Gynecol Obstet. 2015; 291(1): 223–230.
  77. Fan R, Feng F, Yang H, et al. Pulmonary benign metastasizing leiomyomas: a case series of 23 patients at a single facility. BMC Pulm Med. 2020; 20(1): 292.
  78. Nucci MR, Drapkin R, Dal Cin P, et al. Distinctive cytogenetic profile in benign metastasizing leiomyoma: pathogenetic implications. Am J Surg Pathol. 2007; 31(5): 737–743.
  79. Sõritsa D, Teder H, Roosipuu R, et al. Whole exome sequencing of benign pulmonary metastasizing leiomyoma reveals mutation in the BMP8B gene. BMC Med Genet. 2018; 19(1): 20.
  80. Ehata S, Yokoyama Y, Takahashi K, et al. Bi-directional roles of bone morphogenetic proteins in cancer: another molecular Jekyll and Hyde? Pathol Int. 2013; 63(6): 287–296.
  81. Wang RN, Green J, Wang Z, et al. Bone Morphogenetic Protein (BMP) signaling in development and human diseases. Genes Dis. 2014; 1(1): 87–105.
  82. Nuovo G, Schmittgen T. Benign metastasizing leiomyoma of the lung. Diagnostic Molecular Pathology. 2008; 17(3): 145–150.
  83. Goding CR, Arnheiter H. MITF-the first 25 years. Genes Dev. 2019; 33(15-16): 983–1007.
  84. Kawakami Y, Eliyahu S, Delgado CH, et al. Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor. Proc Natl Acad Sci U S A. 1994; 91(9): 3515–3519.
  85. Lopes ML, Carvalho L, Costa A. Benign metastasizing leiomyomas. Acta Med Port. 2003; 16(6): 455–458.
  86. Awonuga AO, Rotas M, Imudia A, et al. Recurrent benign metastasizing leiomyoma after hysterectomy and bilateral salpingo-oophorectomy. Archives of Gynecology and Obstetrics. 2008; 278(4): 373–376.
  87. Arai T, Yasuda Y, Takaya T, et al. Natural decrease of benign metastasizing leiomyoma. Chest. 2000; 117(3): 921–922.
  88. Le Guen P, Poté N, Morer L, et al. Spontaneous regression of miliary pattern after delivery. Benign pulmonary metastasizing leiomyoma. Am J Respir Crit Care Med. 2021; 203(7): 906–907.



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