Virchows Arch (2006) 449: 117120DOI 10.1007/s00428-006-0205-6

CASE REPORT

Eva Markert . Ulrike Gruber-Moesenbacher .Christian Porubsky . Helmut H. Popper

Lung osteomaa new benign lung lesion

Received: 22 December 2005 / Accepted: 23 March 2006 / Published online: 26 April 2006# Springer-Verlag 2006

Abstract Extraskeletal osteomas have not been describedin the lung. Tumors with osseous elements can be found,such as hamartoma and amyloid tumor, and reactive lesionssuch as osseous metaplasia. A 39-year-old male patientwas treated for multiple myeloma and got a bone marrowtransplantation 2 years and a few months before hepresented with a solitary well-circumscribed tumor in theright middle lobe. The patient underwent surgical re-section. The tumor presented with a fibrous capsule andconsisted of mature bone trabecules. Within the tumor,fatty tissue was seen. There were small bone spiculesinterpreted as areas of new bone formation and apposi-tional growth. No amyloid deposition, no immature epi-thelial tubules as in hamartomas, and no normal lungstructure as in osseous metaplasia were seen. Within theosseous elements, a positive reaction was seen with anti-bodies for osteonectin, whereas the reaction for calcitoninwas negative. To the best of our knowledge, this is the firstcase of an osteoma being reported in the lung looking likeany other extraskeletal osteoma. This tumor might havebeen induced by circulating stem cells; however, due toautologous bona marrow transplantation, this cannot beproven.

Keywords Pulmonary osteoma . Hamartoma .Ossification . Osteonectin

Introduction

The most common benign mesenchymal neoplasm of thelung is hamartoma. A primary extraskeletal osteoma of thelung has never been reported. Within its differentials,hamartoma with osseous foci, osseous metaplasia, tracheo-bronchiopathia chondro-osteoplastica, and nodular amy-loidosis or amyloid tumors with ossification have to beexcluded.

Clinical history

In February 2002, the diagnosis of a multiple myeloma(subtype IgA-kappa, stage IIIb, Salmon, and Durie) wasestablished in a 37-year-old male patient, current smoker(34 pack years). He was treated with interferon and gotautologous bone marrow transplantation the same year butrelapsed in 2004. While prepared for a second bonemarrow transplantation, in the absence of respiratorysymptoms, a tumor, 1.7 cm in diameter was detected inthe right upper lobe of the lung and subsequently removed.The tumor was of hard consistency and ossification couldbe identified macroscopically.

Material and methods

The VATS lung tissue specimen including the tumor wascut and a frozen tissue section was done for an intraop-erative diagnosis. To be able to cut the tumor for frozensections, the cut surface was decalcified for 1 min withhydrochloric acid (10%). Then the lung tissue was inflatedwith 10% neutral-buffered formaldehyde solution, fixed,decalcified with EDTA, and processed routinely. Immuno-histochemistry was applied to decalcified paraffin sectionsusing antibodies for osteonectin and calcitonin. Dilution

E. Markert . H. H. Popper (*)Institute of Pathology, Laboratories for MolecularCytogenetics, Environmental and Pulmonary Pathology,Medical University of Graz,Auenbruggerplatz 25,Graz 8036, Austriae-mail: helmut.popper@meduni-graz.atTel.: +43-316-3804405Fax: +43-316-384329

U. Gruber-MoesenbacherInstitute of Pathology,Teaching Hospital Feldkirch,Carinagasse 47, Feldkirch 6800, Austria

C. PorubskyMedical University of Graz,Department of Thoracic and Hyperbaric Surgery,Auenbruggerplatz 29, Graz 8036, Austria

and processing was done as recommended by themanufacturer (Biodesign and Dako).

Results

Macroscopically, an osseous tumor with a diameter of1.7 cm was identified, incompletely encapsulated byfidbrous tissue. Histological examination showed a net-work of mature lamellar bone trabecules with centrallacunes in the tumor. At its periphery, a rim of typicalosteoblasts was seen and areas with immature boneformation, characterized by calcified spicules and closelyattached osteoblasts (Figs. 1 and 2). Within the delicatebone trabecules, there was fatty tissue with dilated thinwalled vessels, similar, as it would be seen in maturelamellar bone. No chondroid cells, no epithelial tubulescould be identified, however, in two areas entrappedbronchioles were seen. Both bronchioles had well-devel-oped mucosa and a smooth muscle layer, which is not seenin hamartoma (Fig. 3). By immunohistochemistry, mostosteoblasts, some osteocytes within the mature bone, andsome histiocyte- and fibroblast-like cells expressed osteo-nectin (Fig. 4). The reaction for calcitonin was negativewithin the osteoma, whereas a few scattered positive cellscould be seen within the lung tissue.

Discussion

Osteomas are benign osseous tumors. They are rare lesionsand most frequently involve the skull, facial bones, or thespine protruding from the underlying bone. On histologicalexamination the osteomas are characterized by mostlybroad trabecules of mature bone. The intratrabecular tissuecan be variably composed of vascular, fibrous, adipose, andhematopoetic elements [2].Extraskeletal osteoma has rarely been reported. In 1997,

Lekas et al. [7] published a case report about an 11-year-old

Fig. 1 Low power micrograph of the osteoma. Note areas of fat aswell as fibrous tissue. The osteoma is well encapsulated by fibroustissue. The surrounding lung is unremarkable. H&E, bar 0.5 mm

Fig. 2 Osteoma of the lung. a The central part is shown with maturelamellar bone. Within the bone, trabecules spicules are still present,which represent the initial stage of the bone formation. In addition,there are activated osteoblasts and osteoclasts, indicating restructur-ing of the bone. In b, the peripheral part of the osteoma is shown.This is characterized by calcified spicules embedded in densefibrous tissue and surrounded by osteoblasts. H&E, bars 50 m

Fig. 3 Central portion of the osteoma with entrapped bronchioles.Regular epithelium and a thin muscular coat, usually 23 cell layerswithout cartilage, characterize these. Notably, bone spicules are seenapproaching the bronchiolar wall and coming close to the surfaceepithelium. H&E, bar 100 m

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girl, who developed an osteoma on the base of her tongue.One case of bilateral choroidal osteoma in association tohistiocytosis X was documented by Kline et al. [6] in 1982.Extraskeletal osteomas were also described in animals,such as a benign osseous lesion in the leg of a cat [5].More likely than osteomas in the lung are pulmonary

hamartomas most frequently discovered in middle aged orelderly adults [11]. A Male predominance of 2:1 is reported[4]. Hamartomas usually manifest as solitary lung nodulesevenly distributed throughout both lungs. Endobronchiallocalization is rare [3]. Histologically, they can be composedof hyaline cartilage, fibromyxoid stroma, smooth musclecells, and adipose tissue. Any of the main tissue types canpredominate. This is cartilage in 51.3%, fibromyxoid stromain 10.5%, and less frequently adipose tissue (2.1%). Inapproximately 40%, smooth muscle cell proliferation can befound; sometimes calcification or bone-formation can beobserved, a predominance of mature bone is exceptionallyrare [3]. One frequent and pathognomonic finding in hamar-toma is the coexistence of mesenchymal elements andepithelial tubules reminiscent of bronchiolar epithelium [10].These tubules are composed of a simple layer of primitivecuboidal epithelium on a basal lamina and embedded in aprimitive mesenchymal stroma. A smooth muscle cell layeris absent. Because of the absence of epithelial elements inour nodule, we were able to exclude hamartoma. Theentrapped bronchioles were characterized by a well-devel-oped bronchiolar epithelium and a muscular layer.Peripheral pulmonary ossification is frequently found in

lungs of elderly people. In this case, bone trabeculesdevelop within the walls of alveoli. They can contain bonemarrow. The lung structure is preserved and no fibrouscapsule is present. In pulmonary ossification, calcificationoften precedes the bone formation. In contrast, our caseshows a de novo formation of bone, which is also sub-stantiated by the expression of osteonectin in the fibroblast-like cells at the periphery of the tumor.A further disorder has to be excluded: tracheobronch-

opathia osteochondroplastica. The ossification is usually

confined to preexisting bronchial or tracheal cartilage, butossous metaplasia can occur [1]. In contrast, the tumorreported herein is a well-circumscribed single nodule with-out cartilage, localized in peripheral lung parenchyma;thus, unlikely to be mistaken for tracheobronchopathiaosteochondroplastica.Nodular amyloidosis might be another source of osseous

metaplasia. Nodular amyloidosis or amyloid tumor couldhave been a consequence of the patients plasmocytoma.Usually, there is deposition of congophilic amyloid, chronicinflammation with foreign body granulomas, and there canbe calcification and even bone formation [8]. In our case,there was no evidence of amyloid deposits in the tumor andsurrounding normal lung tissue.Our patient suffers from multiple myeloma, which in-

duces osteolytic lesions with consecutive hypercalcemia/hyperphosphatemia. There are reported cases of secondaryneoplasm as a consequence of chemotherapy; nevertheless,a benign extraskeletal bone tumor has ever been associatedto multiple myeloma [12].One case of pulmonary ectopic ossification developed in

a dog almost 3 years after allogenic bone marrow trans-plantation. The extensive bone formation was orientedalong the bronchial walls, had normal trabecular architec-ture and marrow with normal cellularity. The authorspostulated a bone formation of donor origin, althoughDNA analysis could not be performed.It may well be that in our patient the osteoma could be

formed by circulating stem cells derived from the bonemarrow [9]; however, due to an autologous transplantation,this cannot be proven. We suppose that this bone tumor inthe patients lung is independent from his major diagnosismyeloma. In our opinion, this tumor is clearly identified asosteoma, although its localization in peripheral lung tissueis extraordinary.

References

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4. Hansen CP, Holtveg H, Francis D, Rasch L, Bertelsen S (1992)Pulmonary hamartoma. J Thorac Cardiovasc Surg 104:674678

5. Jabara AG, Paton JS (1984) Extraskeletal osteoma in a cat.Aust Vet J 61:405407

6. Kline LB, Skalka HW, Davidson JD, Wilmes FJ (1982)Bilateral choroidal osteomas associated with fatal systemic ill-ness. Am J Ophthalmol 93:192197

7. Lekas MD, Sayegh R, Finkelstein SD (1997) Osteoma of thebase of the tongue. Ear Nose Throat J 76:827828

8. Lynch LA, Moriarty AT (1993) Localized primary amyloidtumor associated with osseous metaplasia presenting as bilat-eral breast masses: cytologic and radiologic features. DiagnCytopathol 9:570575

Fig. 4 Immunohistochemistry for osteonection; a focal positivestaining is seen in fibroblast-like cells. Bar, 100 m

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9. Sale GE, Storb R (1983) Bilateral diffuse pulmonary ectopicossification after marrow allograft in a dog. Evidence forallotransplantation of hemopoietic and mesenchymal stem cells.Exp Hematol 11:961966

10. Salminen US (1990) Pulmonary hamartoma. A clinical study of77 cases in a 21-year period and review of literature. Eur JCardiothorac Surg 4:1518

11. van den Bosch JM, Wagenaar SS, Corrin B, Elbers JR,Knaepen PJ, Westermann CJ (1987) Mesenchymoma of thelung (so called hamartoma): a review of 154 parenchymal andendobronchial cases. Thorax 42:790793

12. Zarrabi MH, Rosner F (1989) Second neoplasms in Hodgkinsdisease: current controversies. Hematol Oncol Clin North Am3:303318

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Lung osteomaa new benign lung lesionAbstractIntroductionClinical historyMaterial and methodsResultsDiscussionReferences