HAMARTOMAS OF THE NOSE AND NASOPHARYNX Fiona Graeme-Cook, MB, MRCPI, and Ben Zion Pilch, MD
Hamartomas are easily diagnosed entities when occurring in the lung and gastrointestinal tract. In the nose and nasopharynx, where such lesions are rare, biopsy of a hamartoma containing epithelial proliferation may lead to a misdiagnosis of cancer, with resultant radical and deforming surgery, particularly if they present in adulthood. We encountered three such lesions over 2 years in the Massachusetts Eye Ear Infirmary, and another was retrieved from the recent files. All presented with nonspecific obstructive symptoms of the nose or nasopharynx, and were treated by resection. Follow-up is short, (4 months to 1 year), but in no case has there been recurrence. The clinical diagnosis was malignancy in 2 cases, inflammatory polyp in one. 0 1992 John Wiley & Sons, Inc. HEAD & NECK 1992;14:321-327
T h e word hamartoma, which has become entrenched in general surgical pathology usage, embraces multiple different entities. In its pure form, it is defined’ as an error (hamartia-Gr) in tissue growth, resulting in a tumor-like mass, formed of a disorganized proliferation of tissue indigenous to the area. Willis2 felt that there should be clear-cut evidence of a developmental origin for these masses; therefore, most “bone fide” hamartomas occur in childhood. The wellrecognized cartilaginous “hamartoma” of the lung is not acceptable as a hamartoma by Willis, From the Department of Pathology, Massachusetts General Hospital (Dr. Graeme-Cook), and the Department of Pathology (Dr. Pilch), Harvard Medical School, Boston, Massachusetts. Address reprint request to Dr. Graeme-Cook at the Department of Pathology, Massachusetts General Hospital, Fruit Street, Boston, MA 021 14 Accepted July 23, 1991.
CCC 0148-6403/92/040321-07 $04.00 0 1992 John Wiley & Sons, lnc.
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who considered it to be an acquired benign neoplasm. The fact that hamartomas often do not appear until after birth, or even until adulthood, the difficulty in establishing developmental origin for all these lesions, and the gradual rather than abrupt transition between hamartomas and true neoplasms (eg, in neurofibromatosis) make a precise definition and delineation of hamartomas difficult. Most pathologists accept as a working definition a benign overgrowth of tissue indigenous to the area, forming a mass lesion. Published examples of hamartomas in the nose and nasopharynx comprise for the most part single case reports. The epithelium of the nose, nasopharynx, and paranasal sinuses is derived from the embryonic ectoderm of the nasal placodes, forming the Schneiderian epithelium. The epithelium associated with the published cases of hamartomas has been for the most part squamous, as in the “hairy polyp” of ~hildhood,~ but reports have included cases with glandular epitheli~m.~ We , ~ recently encountered several instances of nasal harmartomas at the Massachusetts Eye and Ear Infirmary; three of our cases appeared to involve nasal placode-type ectoderm, and one was more predominantly mesodermal. MATERIALS AND METHODS
The case histories and follow-up were collected by review of medical records and from the most recent attending physicians; the radiological reports were reviewed. Hematoxylin and eosinstained slides (1 t o 6 in number) were reviewed in all cases. Immunohistochemistry for interme-
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diate filament production and SlOO expression was performed on two cases using the avidin-biotin peroxidase method.
I. A 57-year-old otherwise and previously healthy Portuguese woman was initially seen at the Massachusetts Eye and Ear Infirmary July 1986 with a 5-year history of left-sided nasal stuffiness and discharge, with recent epistaxis. Occupational history revealed that she worked in a plastic and rubber factory involved in the manufacture of sponges. Physical and radiological examination revealed a white mass in the posterosuperior left nasal cavity, which bulged into the nasopharynx, with upward bowing of the superior nasal turbinate and opacification of the left sphenoid and posterior ethmoid sinuses. Chest x-ray, EKG, and routine blood tests were all within normal limits. A left lateral rhinotomy and medial maxillectomy were performed, removing a 5 x 6 cm firm, pale polypoid mass arising on a pedicle from the posterosuperior portion of th eseptum. The patient was well and without recurrent symptoms at follow-up 1 year later.
Case
A 67-year-old woman of Northern European and Italian descent was initially seen at the Massachusetts Eye and Ear Infirmary with a greater than 5-year history of nasal obstruction, more marked on the left than the right, with a recent onset of a choking sensation and increasing paroxysmal nocturnal dyspnea. There was a history of nasal allergy, but these symptoms were unrelieved by her usual allergy medications. Physical and radiological examination revealed a large polypoid mass arising from the posterior left nasal cavity and extending to the posterior wall of the nasopharynx, which was felt to be consistent with an antrochoanal polyp (Figure 1).No bony abnormality was seen. Routine chest x-ray and general preoperative assessment were noncontributory. A left Caldwell- Luc operation was performed, revealing a bilobed pedunculated 5 x 3 cm translucent and pink firm mass arising in the region of the left posterior vomer. The patient is well 10 months after the procedure.
Case 2.
A 78-year-old woman with Parkinson’s disease, a resident within a nursing home, was referred to the Massachusetts Eye and Ear Infirmary after an MRI performed for CNS evaluation revealed a nasopharyngeal mass, in the abCase 3.
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FIGURE 1. CT scan showing polypoid mass arising from the left posterior vomer and extending into the nasopharynx.
sence of sinus disease. In retrospect, the patient had been noted to have nasal obstruction and difficulty breathing at night. The mass was felt clinically to be carcinoma because of its unilateral nature and size. At surgery a mass, greater than 2 cm, was found within the nose essentially blocking both choanae anterior to the nasopharynx. The mass was biopsied. The patient appears well 4 months postoperatively. A 24-year old Turkish male graduate student noticed a growth at the back of his uvula in March 1989. Examination at that time was unremarkable except for what appeared to be a supernumerary uvula originating from the posterior aspect of the soft palate. After follow-up for 9 months, during which time no change was appreciated, an elective excision was scheduled. At surgery a 7 x 1.5 cm polypoid mass was identified arising from the nasal surface of the soft palate; excision was performed. Several days postoperatively he underwent an appendectomy, but is otherwise well 2 months after excision of the palatal mass.
Case 4.
RESULTS Pathology. The first three cases shared many histological features. Each mass formed a lobulated polyp, with a broad leaf-like pattern (Figure 2). In all cases, the surface was covered by a ciliated pseudostratified columnar epithelium. The cores were composed of a fibrous stroma, fo-
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FIGURE 2. Lobulated polyp with broad leaf-like pattern with surface respiratory-type mucosa (original magnification x 31).
FIGURE 3. Prominent muscularized vasculature with numerous small, dilated blood vessels within the polyp stroma (original magnification x 31).
FIGURE 4. Microcysts lined by respiratory-type mucosa with inspissated mucoid content and surrounding pseudo infiltrative glands (original magnification x 50).
FIGURE 5. Cysts with surrounding multiple small disorganized glands (original magnification x 79).
cally cellular, with plump spindle cells, and a lymphoplasmacytic infiltrate, most marked in subepithelial regions. There was a prominent vascular pattern with central muscularized vessels and peripheral arborizing thin-walled di-
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lated vessels (Figure 3). A prominent epithelial component was present in each case, with central cystically dilated spaces lined by flattened to pseudostratified columnar epithelial (Figure 4) and focal squamous metaplasia. The cysts con-
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FIGURE 6. Haphazardly arranged small glands with cuboidal cells and round-oval euchromatic nuclei (original magnification x 200).
FkGURE 7. Lobulated polyp with prominent strorna vessels and Surface focal squamous metaplasia (original magnification
tained inspissated dense pink mucoid material. A striking feature was the proliferation of numerous, small, benign-appearing glands and tubules, lined by cuboidal amphophilic cells with basally oriented small round nuclei. Occasionally these glands appeared more differentiated into seromucinous glands particularly in case 3, which contained fewer glands. These glands were variably arranged in clusters, sometimes surrounding a larger duct-like structure, or more often distributed in a random fashion throughout the tissue, swirling round the cysts, imparting an infiltrative appearance, and leading a a biopsy diagnosis of carcinoma in one case (Figure 5 ) . However, no mitoses, cellular atypia, nor pleomorphism were seen (Figure 6). Immunohistochemistry on paraffin-embedded tissue showed the glands and surface epithelium to express keratins of various molecular weights. S100-positive cells were scattered within the small glands, suggestive of myoepithelial differentiation, with plentiful S100-positive nerve twigs, scattered in a disorganized fashion throughout the tissue. The fourth case differed significantly from cases 1 to 3. Grossly, the tumor consisted of a 2 X 1.4 X 0.4 cm polypoid mass of tan tissue. On routine microscopy, a polypoid configuration was seen with a leaf-like pattern and thick stromal fronds, the surface of which was lined by respiratory-type epithelium, with focal squamous metaplasia. The base of the polyp was composed of dense, hyalinized collagen with numerous blood vessels and scattered seromucinous glands. The fronds were composed of numerous variable-
sized, thin-walled, and partially muscularized blood vessels embedded in a cellular stroma (Figure 7). The stromal cells were loosely aggregated, disorganized, varying from spindle to stellate, with oval to elongate nuclei with fine chromatin and occasional intranuclear vacuoles and scant mitoses. The cytoplasm was wispy, ill defined, and eosinophilic. The cells were embedded within a fine, almost fibrillar matrix, with abundant chronic inflammatory cells (Figure 8). Scattered within the stroma were numbers of large cells with multinucleation, abundant refractile eosinophilic cytoplasm, and obvious cross-striations even on H & E preparations. These resembled mature skeletal muscle morphologically, although occasonal muscle-like cells contained enlarged nuclei. The fibers and mononuclear epithelioid cells were dispersed throughout the polyp without the organization of normal skeletal muscle. In areas the prominence of the vasculature suggested a diagnosis of hemangioma, and in other areas the matrix was dense and almost tendinous. Immunohistochemistry for intermediate filaments confirmed the striated muscle component (desmin, actin, myoglobin positive) (Figure 91, and emphasized the vascular component (Factor VIII) of the polyp.
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X
31).
DISCUSSION
Using the term hamartoma implies that the tisue within the masses is indigenous to the area in which it is found. The epithelial-predominant cases all arose posteriorly close to the midline,
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FIGURE 9. Cross-striations in striated muscle component of polyp (Desmin) (original magnification x 313).
FIGURE 8. Subepithelial chronic inflammatory infiltrate, blood vessels, and numbers of large striated muscle fiber-like cells (original magnification x 200).
on the septum or anterior nasopharynx. All were composed of tissue that is normally present in this region- surface epithelium, seromucinous glands, fibrous stroma, and muscularized vasculature. We feel, therefore, that these cases are hamartomas. The fourth case contained skeletal muscle and arose on the nasal surface of the soft palate. We could find no cases of hamartomas in the literature from this region containing skeletal muscle, but skeletal muscle is an intrinsic part of the soft palate. The polyp contained disorganized tissue components, all indigenous to the area, and therefore can be considered a hamartoma. The differential diagnosis of such masses must include neoplastic processes. In cases 1 to 3, such tumors as minor salivary gland and nasal adenocarcinomas must be considered. The growth pattern, overall architecture, lack of significant atypia, and lack of expansile growth or true infiltration of surrounding structures all support a benign diagnosis. Although he distinction may be dificult on small biopsy fragments, the bland cytology, the long history in all cases, and the lack of correlation with any known pattern of malignancy may be of value in
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designating these polyps on biopsy as benign, possibly “developmental.” Inflammatory lesions, including antrochoanal polyp, also enter the differential diagnosis. The proliferation of glands, disorganization of the elements, and absence of sinus involvement help to exclude inflammatory polyps. In case 4, rhabdomyomatous processes must be excluded. Fetal rhabdomyoma is well recognized in a head and neck location,6 as is adult rhabd~myoma.~>’ The maturity of the myofibers is inconsistent with a rhabdomyoma of fetal type, and the mixed spindle cell and myofiber pattern is not that of the adult rhabdomyoma, where large epithelioid cells usually comprise almost the entire mass. This mass does resemble somewhat the so-called “vaginal” or “genital rhabdomyoma,” arising in the vagina in adults, composed of spindle cells and myofibers in a polypoid configuration. There is debate, however, as to whether this entity is in fact harmartomatous rather than neopla~tic.~-’lThe diagnosis of botryoid rhabdomyosarcoma is excluded in our case by the absence of hyperchromatic malignant cel1s.l2 The differentiation of this lesion from a benign mesenchymoma is probably an exercise in terminology. The mesenchymoma is possibly less well organized and may contain elements foreign to the area. However, a diagnosis of benign mesenchymoma would be very reasonable in case 4, as some would consider all benign mesenchymomas to be hamartomas. Because these masses are not clearly neoplastic and are definitely not inflammatory, they are best described as developmental in origin, ie,
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Table 1. Epithelial and mesenchymal hamartomas in the literature. Author
Age
Epithelial hamartornas 8ailie4 26 yr Zarbo5 32 yr Present series 56 yr 67 yr 78 yr Birt and 1 mo Jones17 19 mo wilIisig Brandenbergla F0xwe11~~ Mahindra”
3 yr 10 d
2 mo
Mesenchyrnal hamartomas Majurnder” 19 yr 10 yr Mahindra” 26 yr Kac kerZ0 12 yr Day”‘ 1 Yr Present series 24 yr
Epithelium
Mesenchyme
Schneiderian Schneiderian Schneiderian Schneiderian Schneiderian Skin Squamous (parathyroid) Keratinizing Squarnous Keratinizing Squamous ? Hairy polyp
-
-
Schneiderian
Cartilage -
-
-
Vascular Vascular Vascular Vascular Lymphatic Skeletal Muscle and blood vessels
arising as a result of an aberration of tissue growth. In the nose and nasopharynx, developmental masses are traditionally divided into three groups: teratomas, dermoids or teratoids, and hamartomas. The most clearly neoplastic of these is the teratoma, derived from all three germ cell laryers, and containing tissue that may be foreign to the area. In the head and neck these are well-recognized, if rare, entities, and can take the form of an “epignathus,” occasionally with well-formed organs and limbs of a “parasitic fetus”.13 The second category, dermoids or teratoids, contains masses that are formed form skin and its appendages, cartilage, bone, muscle, and salivary glands, and form the group known as “hairy p01yps.”~These occur most commonly in infancy, and have been considered hamartomatous by some, despite the ectodermal component not being indigenous to the area.14-16 Reports of true hamartomas of the nose and nasopharynx are exceedingly rare. If hairy polyps are excluded as not being true hamartomas, but rather being dermoids or teratoids, then only occasional single reports exist (Table 1).
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Bailie4 and Zarbo5 each reported a case with features similar to ours: similar location and presentation with a histologic picture of Schneiderian epithelium with seromucinous glands, ducts, and cysts within a vascular collagenous stroma. Possible cases have been reported that included elements not indigenous to the region, these elements being considered metaplastic, such as keratinizing squamous epithelium, bone, by definicartilage, and p a r a t h y r ~ i d . l ~ -These ~’ tion may not represent true hamartomas. Mesenchymal-predominant hamartomas, though quoted t o be more common than epithelial-predominant hamartomas, are poorly represented in the literature in the nose and nasopharynx.16,20,21problems arise again with nomenclature, as angiomatous hamartomas might be considered angiomas or vascular malformations by other pathologists.22 Most reports are of masses consisting of the overproduction of one mesenchymal element, rather than of all or several of those mesenchymal elements indigenous to the area.23 Hamartomas of the nose and nasopharynx are exceedingly rare, if Willis’ criteria are adhered to. We report four cases of hamartomas: three predominantly epithelial, increasing those reported in the literature to five (by strictest criteria), and 1predominantly mesenchymal, whose skeletal muscle component has hitherto not been reported in this region.
REFERENCES
1. Albrecht E. Ueber trube schwellung und fettdegeneration verhandl d. dsutsch. Path Gesellsch, Jena, 1904; 15:63-71. Quoted in Willis: Borderland of embryology (See reference 2). 2. Willis, RA.Hamartoma and hamartomatous syndromes. In: Borderland of embryology and pathology. Chapter 9, 2nd ed. Washington: Butterworth. 1962:351-392. 3. Brown-Kelly A. Hairy or dermoid polypi of the pharynx and nasopharynx. J Laryngol Rhinol Otol 1918;33: 65-70. 4. Bailie EU, Batsakis JG. Glandular (seromucinous) hamartoma of the nasopharynx. Oral Surg 1974;38:760762. 5. Zarbo RJ,McClatchey KD. Nasopharyngeal hamartoma: report of a case and review of the literature. Laryngoscope 1983;93:494-497. 6. Dehner LP, Enzinger FM, Font RL. Fetal rhabdomyoma. Cancer 1972;30:160- 166. 7. Reitter GS. Rhabdomyoma of the nose. JAMA 1921; 7622-23. 8. Scrivner D, Meyer JS. Multifocal recurrent adult rhabdomyoma. Cancer 1980;46:790- 795. 9. Gad A, Eusebi V. Rhabdomyoma of the vagina. J Pathol 1975;115:179-181. 10. Gold JH, Bossen EH. Benign vaginal rhabdomyoma. Cancer 1976;37:2283-2294.
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11. Leone PG, Taylor HB. Ultrastructure of a benign polypoid rhabdomyoma of the vagina. Cancer 1973;31:14141417. 12. Enzinger FM, Weiss SW. In: Soft tissue tumors. Chapter 18, 2nd ed. St Louis: Mosby. 1988:448-488. 13. Ehrich WE. Teratoid parasites of the mouth. Am J Ortho 1945;31:650-659. 14. Bicknell MR. “Hairy polyp” of the nasopharynx. J Laryngo1 Otol 1967;131:1045- 1048. 15. Ladapo AA. A case of benign congenital hamartoma of the nasopharynx. J Laryngol Otol 1978;92:11411145. 16. Mahindra et al. Hamartoma of the nose. J Laryngol Otol 1978;92:57-60. 17. Birt BD, Jones EB. Respiratory distress due to nasopharyngeal hamartoma. Br Med J 1969;3:281-282.
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18. Brandenburg JH, Finch WW, Lloyd R. Cystic hamartoma of the nasopharynx. Am Acad Ophthalmol, Otolaryngol 1977;84:152- 153. 19. Willis RA. Some unusual developmental heterotopias. Br Med J 1968;3:267-272. 20. Kacker SK, DasGupta G. Hamartomas of ear and nose. J Laryngol Otol 1973;87:801-805. 21. Majumder NK et al. Hamartoma of nasopharynx. Laryngol Otol 1977;91:723-727. 22. Day LH, Arnold GE. Rare tumors of the ear, nose, and throat: second series: uncommon benign tumors of the head and neck. Laryngoscope 1971;81:1138-1174. 23. Puri ND, Vaid A, Sawhney KL. Fibrolipoma of the nasopharynx. J Zndian Med Assoc 1979;72:215-216. 24. Foxwell PB, Kelham BH. Teratoid tumours of the nasopharynx. J Laryngol Otol 1958;72:647-657.
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