Auris Nasus Larynx 27 (2000) 179 – 183 www.elsevier.com/locate/anl
Invasive verrucous carcinoma: a temporal bone histopathology report Hideo Hagiwara a, Takeharu Kanazawa a, Kazuhiro Ishikawa a, Takeshi Fujii b, Ken Kitamura c,*, Yoshihiro Noguchi c, Yukiko Iino d a
Department of Otolaryngology, Jichi Medical School, Minamikawachi-machi, Tochigi 329 -0498, Japan b Department of Pathology, Jichi Medical School, Minamikawachi-machi, Tochigi 329 -0498, Japan c Department of Otolaryngology, Tokyo Medical and Dental Uni6ersity, 1 -5 -45 Yushima, Bunkyo-ku, Tokyo 113 -8519, Japan d Teikyo Uni6ersity, Kaga, Itabashi-ku, Tokyo 173 -0003, Japan Received 3 June 1999; received in revised form 3 July 1999; accepted 16 July 1999
Abstract Only nine cases of primary verrucous carcinoma of the temporal bone have been reported in the English literature. We describe histopathologic findings in a 78-year-old man dying of intracranial complications of primary verrucous carcinoma of the external auditory canal. Following autopsy the temporal bone was prepared for light microscopic examination. The temporal bone was serially sectioned horizontally after fixation, decalcification, and embedding, and each 10th section was stained with hematoxylin and eosin and examined by light microscopy. The carcinoma originated from the external auditory canal, infiltrating the mastoid cavity, the middle ear, tissue adjacent to the internal carotid artery, and the posterior cranial fossa, where it invaded the right cerebellum and produced an abscess. The labyrinth and internal auditory canal were not infiltrated. Metastasis to lymph nodes or distant sites was not identified. In the present case, the verrucous carcinoma originating from the external auditory canal extended into the posterior cranial fossa, while it did not invade the membranous labyrinth. © 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Verrucous carcinoma; Temporal bone; Histopathology; Intracranial complications
1. Introduction
2. Case report
Verrucous carcinoma is a highly differentiated variant of squamous cell carcinoma. It is a slowly growing, papillary squamous neoplasm which is often extensive and may infiltrate deeply, but rarely metastasizes, even to local lymph nodes. The most common sites of verrucous carcinoma in the head and neck are the oral cavity and larynx; however, it is very rare in the temporal bone [1]. To our knowledge, only nine cases of verrucous carcinoma of the temporal bone have been reported in the English literature [2 – 6]. We examined the temporal bone histopathology from a patient with verrucous carcinoma of the external auditory canal (EAC).
A 78-year-old man was admitted to Jichi Medical School Hospital with the complaints of vomiting and fever. He claimed a profound hearing loss in the left ear since early childhood and also gave a history of a progressive hearing impairment accompanied by recurrent purulent otorrhea in his right ear since his youth. He had noted a chronic discharge from his right ear for 10 years until he sought medical attention at age 77. He was diagnosed with cholesteatoma, but declined surgical intervention. On his first admission, physical examination showed cervical rigidity and Kernig’s sign. The right EAC was filled with thick secretions, granulation tissue, and a whitish warty tissue proliferation. Facial paralysis was not present. No cervical lymphoadenopathy was palpable. An audiogram demonstrated no detectable hearing in either ear.
* Corresponding author. Fax: +81-35803-0146. E-mail address:
[email protected] (K. Kitamura)
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Nystagmus was not detected. Computed tomography (CT) (Fig. 1) demonstrated a large bony defect in the right mastoid with extension to the temporomandibular joint, and erosion of the posterior surface of the petrous pyramid. T1-weighted magnetic resonance imaging (MRI) with gadolinium showed multiple ring-enhancing cerebellar lesions, presumably abscesses secondary to middle ear infection. Two biopsy specimens from the granulation tissue in the external auditory canal showed squamous epithelium with keratosis and inflammatory cell infiltration without malignant change. Examination of a third specimen established a diagnosis of verrucous carcinoma. Enlargement of the cerebellar abscesses was held in check by intravenous antibiotics, though the patient refused any additional treatment and died of cerebellar abscess 20 months after the diagnosis of verrucous carcinoma. An autopsy was performed, and the right temporal bone was removed for histologic study. The cerebrum was diffusely swollen, with a flattened surface and slight congestion. The arachnoid covering of the right cerebellar hemisphere was adherent to the skull base. In the right cerebellar hemisphere, two cystic lesions were identified after the adhesion was removed. A large (37× 20 mm) abscess had a wall including scattered keratinizing squamous cells, while a smaller lesion (23× 20 mm) was associated with invasive verrucous carcinoma. This suggests that the abscesses were formed by infection secondary to carcinoma infiltration. The medulla oblongata was compressed and flattened because of the swollen cerebellum. Metastasis to lymph nodes or distant sites was not identified. After autopsy the right temporal bone was fixed in 10% formaldehyde. It then was decalcified, embedded in celloidin, serially sectioned horizontally at 20 mm
thickness, and every 10th section was stained with hematoxylin and eosin and examined by light microscopy.
3. Histopathology of the temporal bone The verrucous carcinoma invaded the EAC, tympanum, and mastoid with marked surface keratinization, parakeratosis, a pushing border extending into underlying bone, absence of cellular atypia, and a mixed chronic inflammatory infiltrate (Fig. 2). The tumor appeared to originate from the EAC. The posterior wall of the EAC was diffusely destroyed by verrucous carcinoma. The protympanum was invaded by tumor, and the tumor infiltration as well as inflammatory cells were seen in the tissue adjacent to the internal carotid artery. The petrous portion of the temporal bone was also extensively involved by carcinoma, which extended into the posterior cranial fossa to invade the right cerebellar hemisphere. Associated with this process were multiple cerebellar abscesses. Neither the bony nor the membranous labyrinth were infiltrated by tumor, nor were the internal auditory canal, facial nerve, or vestibulocochlear nerve. The EAC and mastoid air cells were filled with extensive keratin and granulation tissue with extensive bony erosion. The tympanic membrane, malleus, and incus were absent; however, the footplate of the stapes was intact (Fig. 3). A portion of the chorda tympani was identified and its nerve fibers appeared normal. Connective tissue and new bone formation were noted in the peri- and endolymphatic space in both the cochlea and the vestibule; this appeared to have resulted from labyrinthitis. The organ of Corti was severely atrophied throughout the cochlea, and hair cells appeared absent throughout (Fig. 4). The cristae and maculae showed advanced degeneration. The sensory epithelia of the cristae and maculae demonstrated no remaining sensory cells.
4. Discussion
Fig. 1. Axial computed tomography scan of the temporal bone. A soft tissue density is seen in the right temporal bone with a large bony defect (arrow head) of the petrous pyramid.
The pathologic diagnosis of verrucous carcinoma is extremely difficult, and typically requires multiple biopsies. A small or superficial biopsy specimen often reveals only hyperkeratosis, acanthosis, and apparently benign papillomatosis [7]. Increased keratinocytes and nuclear area may be the only clue to malignancy [8]. In the present case multiple biopsies were performed in order to achieve a conclusive diagnosis of verrucous carcinoma. In a series of 25 patients with temporal bone carcinoma, more than half had a history of chronic otits media [9]. Six of the ten reported verrucous carcinoma
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Fig. 2. A: The posteior wall of the external auditory canal (E) is infiltrated by verrucous carcinoma cells with marked surface keratinization and parakeratosis. A pushing border with underlying bone is apparent. Normal squamous epithelium (*) also is seen (horizontal section; HE, magnification× 40). B:High power view of the rectangular area of the Fig. 2A. An intact basement membrane is noted in spite of the deeply involved squamous cells with prominent nucleoli.( ×100)
cases, including the present case, were reported to have chronic otitis media [2 – 6]. Four of them had undergone ear surgery in the past. According to Proops et al. [4] increased duration of chronic suppuration resulted in a greater risk of carcinoma. In this case the patient had noted chronic suppuration for more than 10 years. In another reported case an 80-year-old woman frequently picked at her ear with a hairpin [5]. A moist environment or local irradiation also appears conducive to development of these tumors [3 – 5]. The primary lesions of verrucous carcinoma in the temporal bone were in the EAC (five cases), a postoperative defect (four cases), or middle ear (one case).
Involvement of the membranous labyrinth by primary malignancy of the temporal bone, especially squamous cell carcinoma, has rarely been reported [10]. Primary sarcoma of the middle ear also dose not invade directly into the inner ear with destruction of the bony labyrinth [11]. Metastatic tumors usually involve the temporal bone via hematogenous dissemination, but invasion of the inner ear is uncommon [11]. In two previously reported cases of temporal bone verrucous carcinoma, extension occurred into the inner ear [3,4]. Woodson et al. [3] described a case with invasion of the cochlea but preservation of the bony labyrinth. However, the route of invasion in this case was not men-
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Fig. 3. Verrucous carcinoma (arrow) infiltrates the mucosa of the middle ear. Fallopian canal (F) is dehiscent and surrounded by inflammatory cells. Vestibule is filled with connective tissue formation. S; stapedial footplate (horizontal section; HE, magnification × 20)
tioned. In our case, the carcinoma does not infiltrate the bony capsule or the membranous labyrinth despite extension from the mastoid cavity to the cerebellum. This suggests a degree of biologic resistance to neoplasms intrinsic to the bony and membranous labyrinth, as previously proposed by Schuknecht et al. [11]. The most common route of invasion is via the
internal auditory canal for both primary or metastatic tumors of the temporal bone. In most such cases, the tumor infiltrated from the internal auditory canal to Rosenthal’s canal or as far as the proximal half of the osseous spiral lamina [10]. The role of radiotherapy in the treatment of verrucous carcinoma remains controversial. Radiotherapy has not been considered a treatment of choice, and to some authors it is contraindicated because in their view it carries a risk of anaplastic transformation to a more aggressive squamous cell carcinoma [12]. However, Tharp and Shidnia [13] have reported patients with verrucous carcinoma of the head and neck who did not demonstrate anaplastic transformation after treatment with irradiation. According to their literature review, anaplastic transformation occurred in 7% of patients who underwent irradiation, and transformation can also occur after surgery without irradiation. However, the rate of local control with irradiation is less than 50%, while with surgery it is 74–86% [13]. Therefore, surgery is the preferred therapeutic modality. Radiotherapy can be used in patients with advanced disease or in patients who are poor surgical candidates. Prognosis of patients with verrucous carcinoma of the temporal bone depends on the extension of the tumor. Cases with extratemporal infiltration exhibit a poor prognosis. Four of these six cases died within 20 months of diagnosis, while of the four cases with the growth within the temporal bone three showed no evidence of disease progression for more than 4 years, and the outcome of the fourth case is unknown [2–6].
Fig. 4. Extensive ossification in the perilymphatic space of the basal turn and in the endolymphatic space of the middle turn is seen. The organ of Corti and spiral ganglion cells were missing throughout the cochlea. (horizontal section; HE, magnification ×5)
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