Aneurysmal Bone Cyst of the Larynx Presenting With Hypoglottic Obstruction.

A Case Report and Review of the Literature

The human larynx is composed of cartilaginous tissue that early in adulthood progressively undergoes ossification. This process is initially endochondral, and by the third decade it can fully replace the native cartilaginous framework of the organ. In keeping with the ossification, osteocartilaginous tumors may occur in the larynx, including chondrosarcoma, chondroma, and, less frequently, osteoma, osteosarcoma, and giant cell tumor.[1-3] Aneurysmal bone cyst (ABC) appears within this subset, although it is an underreported finding with a paucity of cases reported in the literature.[3,4] In this article, we present a new case of laryngeal ABC and discuss its diagnostic problems and practical clinical implications.

REPORT OF A CASE

A 22-year-old man was admitted to the local Division of Otolaryngology for breathing discomfort that had lasted some months. The man's past medical history was unremarkable. He had no previous history of trauma to the neck or intubation. Recently, he complained of shortness of breath following mild exercise. No voice changes were noted. Physical examination was unremarkable. Pertinent laboratory examinations, including a serum calcium level, were within normal limits. Routine radiographs of the chest showed no significant abnormality of the mediastinal profile. Laryngoscopy revealed a polypoid lesion implanting on the anterior aspect of the subglottic cone. Biopsy fragments were taken, fixed in 4% formaldehyde, and processed routinely. Microscopic examination of hematoxylin-eosin-stained sections showed an intimate admixture of mononuclear and multinucleated giant cells embedded in either a fibrous or a loosely textured background substance. Hemosiderin deposits were present as well. A panel of antibodies was applied to paraffin sections, directed to wide-spectrum keratins (AE1/AE3, dilution 1: 100), desmin (1:4000), vimentin (1:100), smooth muscle actin (1A4, 1:12000), muscle-specific actin (HHF35, 1:1000), S100 protein (1:200), and CD68 (KP1, 1:400). All the antibodies were monoclonal, except anti-S100 protein, which was polyclonal. Antibodies against keratins and actins were purchased from Dako Corporation (Santa Barbara, Calif), and the remainder were supplied by BioGenex (San Ramon, Calif). The immunoperoxidase study was performed with the avidin-biotin complex method, using diaminobenzidine as the chromogen and following directions published elsewhere.[5] Appropriate external and internal controls were used to assess the quality of immunostaining. Both the mononuclear and giant cells were immunopositive for vimentin and CD68; reactions for all the other antibodies tested were negative.

The patient underwent frontal coronal resection of the hypoglottis. The specimen measured 3 cm in its largest dimension (Figure 1) and showed a polypoid, soft gray mass attached to the anterior aspect of the mucosa and protruding into the lumen. The surface was slightly lobulated. Processing was accomplished by fixing the whole specimen in 4% formaldehyde for 72 hours and then placing it in a slow-acting decalcifier (EDTA) until optimal demineralization was obtained. One-centimeter-thick slices were then placed in larger tissue cassettes for dehydration, clearing, and paraffin infiltration. Five-nanometer tissue sections were trimmed using a special microtome manufactured by LKD (Bremma, Sweden). Microscopic examination of hematoxylin-eosin-stained sections revealed that the lesion was attached to the hypoglottic mucosa with no evidence of anatomic relationship to the laryngeal cartilage framework.

[ILLUSTRATION OMITTED]

Histologically, osteoclast-like giant cells, spindle cells, and lymphocytes were haphazardly scattered within a myxoid or collagenized background substance showing chondro-osteoid changes. Spaces filled with blood and lined by giant cells were common (Figure 2). Giant cells were admixed with osteoid tissue (Figure 3, A) or with mitotically active mononuclear cells (Figure 3, B).

[ILLUSTRATIONS OMITTED]

No further therapy was administered. Follow-up at 1.5 years was negative for lesion recurrence.

COMMENT

Aneurysmal bone cyst is a rapidly growing but benign lesion occurring in the long bones and vertebrae of adolescents.[6] Classic microscopic features include proliferating spindle cells and osteoclast-like giant cells lining pseudovascular cavernous spaces; a fibromyxoid background substance with scattered chondroid and osteoid changes often may be recognized. Deviating histologic patterns may occur based on the proportion between the proliferating component and the aneurysmal-like cystic space. The histogenesis of ABC remains controversial, since in as many as half the cases it is associated with other bone lesions, including giant cell tumors, chondroma, and osteosarcoma. For this reason, ABC is also regarded as a reactive tissue pattern rather than a true entity. In addition to these histologic findings, orthotopic ABC has a characteristic radiographic appearance due to reactive peripheral bone changes that induce a radiolucent shell.

Aneurysmal bone cyst is rare in extraskeletal locations, especially if compared to the incidence of other proliferative lesions of chondro-osteoid lineage that can occur outside bones. Only a few convincing cases of soft tissue ABC have been reported, arising in the superficial soft tissues of the groin, trunk, and within an artery.[7-9] Similar to their bony counterpart, ABC-like changes also have been noted associated with other lesions of soft tissues, such as myositis ossificans or fasciitis.[10]

Aneurysmal bone cyst of the larynx appears to be rare. To the best of our knowledge, only 3 cases have been published in the English medical literature. In the study by Schilling et al,[3] 2 cases of ABC arising from the thyroid cartilage are described. The patients were a 53-year-old woman and a 40-year-old man who had a laryngeal commissure and a vocal cord lesion, respectively.[3,4] Both patients sought treatment for altered voice, shortness of breath, or both. The gross pattern was expansile and noninfiltrating, but in one patient airway obstruction was critical at the time of surgery. Histologically, the lesions recapitulated the basic features of customary ABC. Treatment was conservative and follow-up was uneventful in both cases. Sercarz et al[4] described a case of ABC arising from the cricoid cartilage. The patient was a 36-year-old man complaining of progressive shortness of breath, who eventually needed emergency tracheostomy for acute airway obstruction. The lesion destroyed the right cricoid cartilage and was successfully cured by simple excision with voice preservation.

In this article, we present a new case of laryngeal ABC that occurred in the hypoglottis. The lesion had an exophytic growth pattern, thus causing progressive obstruction of air flow, shortness of breath, and local discomfort. The location of the lesion allowed coronal resection with sparing of the vocal cords. Serial sectioning of the whole specimen revealed no anatomic relationship of ABC to the cricoid perichondrium. Rather, microscopic examination of the lesion pedicle would indicate that the lesion arose from the subglottic mucosal stroma. Tissue sections recapitulated the characteristic microscopic features of customary ABC. Mitotic activity also could be documented, but atypical mitoses and pleomorphism were not observed.

The differential diagnosis of ABC of the larynx is the same as when ABC occurs in bones or in the soft tissue. In particular, microscopic entities that may be confused with ABC include lesions featuring giant cells and spindle cells within a prominent vascular pattern. Giant cell tumor has multinucleated osteoclast-like giant cells, often displaying innumerable nuclei ([is greater than] 20 up to 100), and usually does not have the characteristic fibromyxoid milieu with chondroid or osteoid changes. Giant cell tumor of the larynx has been described.[2] Although there is no single valid microscopic criterion in separating ABC from true giant cell tumor, since both lesions share several features and may even be associated, true giant cell tumors are generally less cystic than ABC and their multinucleated cells usually display many more nuclei than those of ABC. Laryngeal giant cell tumors apparently pursue an indolent course compared to their bone homologue, considering that none of the reviewed cases with available follow-up recurred or metastasized. Vascular tumors may be recognized by virtue of their endothelial, rather than histiocytic, lining of cystic spaces. The problematic 3-dimensional space reconstruction of fragmented tissue specimens obtained at laryngoscopy may, however, create some irreducible difficulties. In these cases, the diagnosis remains one of exclusion. The most important differential diagnosis is with telangiectatic osteosarcoma, however, which features a disorderly proliferation of clearly malignant atypical cells in a vascular background.

The origin of laryngeal ABC is largely a matter of speculation. The occurrence of 3 of the 4 reported cases in males, including our observation, could suggest that ABC is related to the extent of cartilage ossification, a process that starts and terminates earlier in men than in women. This view could be indirectly supported by the noticeable incidence of bony lesions such as giant cell tumor in males.[2] On the other hand, Schilling et al[3] claimed that the tensile forces exerted by the laryngeal skeletal muscles, especially the vocalis muscles, on the local perichondral or periosteal surfaces may contribute to focal changes in the ossified cartilage, predisposing to tissue turnover and secondary neovascularization. In our case, lack of any microscopic relationship with the cricoid cartilage would suggest that ABC changes might alternatively arise within the submucosal tissue, perhaps secondary to a focus of reparative bone metaplasia.

In summary, we report a new case of ABC that occurred in the subglottis of a young patient. Unlike the other reported cases, the growth pattern was polypoid and showed no evidence of connection to the cricoid cartilage. Aneurysmal bone cyst should be considered in the differential diagnosis of a laryngeal lesion containing giant cells. In particular, it has to be distinguished from telangiectatic osteosarcoma. Since ABC has a totally benign course, therapy should be conservative. As for bone lesions, radiation therapy is contraindicated.[3] Based on the available literature and this new observation, local surgical treatment aimed at preservation of speech functions may be recommended, even for lesions arising close to or from the vocal cords.

The authors thank Mario Luna, MD, Department of Pathology, M. D. Anderson Cancer Center, Houston, Tex, for reviewing the original histologic material. The friends and members of the Arkadi M. Rywlin Histopathology Club are also gratefully acknowledged for providing their valuable opinions and suggestions on this case.

References

[1.] Batsakis JG, Fox JE. Supporting tissue neoplasms of the larynx. Surg Gynecol Obstet: 1970;131:989-997.

[2.] Martin PC, Hoda SA, Pigman HT, Pulitzer DR. Giant cell tumor of the larynx: case report and review of the literature. Arch Pathol Lab Med. 1994;118: 834-837.

[3.] Schilling HE, Neal GD, Nathan M, Aufdemorte TB. Aneurysmal bone cyst of the larynx Am J Otolaryngol 1986;7:370-374

[4.] Sercarz JA, Robert M, Atessi D, Fu YS, Calcaterra TC. Aneurysmal bone cyst of the cricoid cartilage: an unusual cause of subglottic stenosis. Head Neck. 1991; 13:457-460.

[5.] Nadji M, Morales AR. Immunoperoxidase techniques. In: Silverberg SS, ed. Principles and Practice of Surgical Pathology. New York, NY: Churchill-Livingstone; 1990;103-118.

[6.] Fechner RE, Mills SE. Tumors of the Bones and Joints. Washington, DC: Armed Forces Institute of Pathology; 1993. Atlas of Tumor Pathology; 3rd series, fascicle 8.

[7.] Rodriguez-Peralto JL, Lopez-Barea F, Sanchez-Herrea S, Atienza M. Primary aneurysmal cyst of soft tissues (extraosseous aneurysmal cyst). Am J Surg Pathol. 1994;18:632-636.

[8.] Lopez-Barea F, Rodriguez-Peralto JL, Burgos-Lizaldez E, Alvarez-Linera J, Sanchez-Herrea S. Primary aneurysmal cyst of soft tissue: report of a case with ultrastructural and MRI studies. Virchows Arch. 1996;428:125-129.

[9.] Riccioni L, Foschini MR Extraosseous aneurysmal bone cyst. Tumori. 1996; 82:485-487.

[10.] Dahlin DC, McLeod RA. Aneurysmal bone cyst and other nonneoplastic conditions. Skeletal Radiol. 1982;8:243-250.

Accepted for publication November 8, 2000.

From the Division of Anatomic Pathology, City Hospital, Conegliano (TV), Italy (Drs Della Libera, Bittesini, and Falconieri); and the Department of Pathology, M. D. Anderson Cancer Center, Houston, Tex (Dr Redlich).

Reprints: Giovanni Falconieri, MD, Division of Anatomic Pathology, City Hospital, I 31015 Conegliano TV, Italy (e-mail: [e-mail]).