Abstract
Objectives
To assess the clinicopathologic correlations of otologic complaints in patients with acute lymphocytic leukemia.
Design
Otologic complaints and histologic findings were evaluated in 25 temporal bones of 13 acute lymphocytic leukemia patients.
Results
Nine patients had a history of otologic complaints, including hearing loss, otalgia, otorrhea, and vertigo in 5, 3, 3, and 2 patients, respectively. Hemorrhage was most commonly observed in the middle ear (6 patients, 9 temporal bones) and was also observed in cochlea (4 patients, 4 temporal bones), and vestibule (6 patients, 6 temporal bones). Leukemic infiltration was observed in the petrous apex (13 patients, 24 temporal bones), middle ear (7 patients, 14 temporal bones), cochlea (3 patients, 4 temporal bones), vestibule (3 patients, 4 temporal bones), and internal auditory canal (5 patients, 8 temporal bones). Inflammatory changes were observed in the cochlea (5 patients, 8 temporal bones) and vestibule (5 patients, 8 temporal bones). Middle ear effusion containing floating tumor cells was observed in 4 temporal bones of 3 patients. Irreversible histopathologic changes of the middle ear, such as the destruction of the ossicles, perforation of the tympanic membrane, and granulation tissues were observed in 5 temporal bones of 4 patients.
Conclusions
Ear involvement is common in acute lymphocytic leukemia patients. With prolonged survival due to the progress of treatment, the diagnosis and treatment of nonhematopoietic system symptoms, such as ear problems due to acute lymphocytic leukemia, have become more important.
1
Introduction
It is reported that patients with leukemia occasionally have hearing loss, tinnitus, and/or vertigo as initial clinical complaints or during follow-up . The proportion of patients with leukemia having definite otologic signs or symptoms was reported to be 32% by Shanbrom and Finch (1958) and 48% by Paparella et al (1973). In contrast, leukemic infiltration of the ear is infrequent in the clinical setting, and only anecdotal cases have been reported to date . Clinicians need to clearly understand the clinicopathologic correlations of otologic symptoms in patients with leukemia. A human temporal bone study of a large number of cases specific to acute lymphocytic leukemia (ALL) has not been conducted. This study was performed in a large number of temporal bones from patients with ALL to determine the histopathologic correlations of clinical findings.
2
Materials and methods
Autopsy reports of 1000 patients from the temporal bone collection at the University of Minnesota were screened to select cases with ALL. Twenty-five temporal bones from 13 patients were obtained.
Clinical details of these 13 patients were as follows. All the patients were white. There were 8 males and 5 females in this group with an age range of 3 to 67 years and an average age of 17.5 years. Five patients received chemotherapy and radiation therapy, 7 received chemotherapy, and 1 received only palliative therapy. Five patients were administered ototoxic drugs. Eleven patients died of infection, 1 of hemorrhage, and 1 of hepatic coma. The range of survival was 1 to 64 months with an average survival period of 24.3 months.
Temporal bones were removed at autopsy less than 24 hours after death and were fixed in formalin solution. Each bone was decalcified, embedded in celloidin, and serially sectioned in the horizontal plane at a thickness of 20 μm. Every 10th section was stained with hematoxylin-eosin and mounted on a glass slide. We examined each temporal bone under light microscopy for the presence of leukemic infiltration, hemorrhage, and inflammatory changes, and noted the anatomic site of involvement. Clinical records were reviewed to retrieve the clinical course, treatment methods, and clinical otologic complaints reported after the initial diagnosis of leukemia. We reviewed autopsy reports to determine the proportion of other organs with leukemic cells and then considered the histopathologic correlations of clinical findings.
2
Materials and methods
Autopsy reports of 1000 patients from the temporal bone collection at the University of Minnesota were screened to select cases with ALL. Twenty-five temporal bones from 13 patients were obtained.
Clinical details of these 13 patients were as follows. All the patients were white. There were 8 males and 5 females in this group with an age range of 3 to 67 years and an average age of 17.5 years. Five patients received chemotherapy and radiation therapy, 7 received chemotherapy, and 1 received only palliative therapy. Five patients were administered ototoxic drugs. Eleven patients died of infection, 1 of hemorrhage, and 1 of hepatic coma. The range of survival was 1 to 64 months with an average survival period of 24.3 months.
Temporal bones were removed at autopsy less than 24 hours after death and were fixed in formalin solution. Each bone was decalcified, embedded in celloidin, and serially sectioned in the horizontal plane at a thickness of 20 μm. Every 10th section was stained with hematoxylin-eosin and mounted on a glass slide. We examined each temporal bone under light microscopy for the presence of leukemic infiltration, hemorrhage, and inflammatory changes, and noted the anatomic site of involvement. Clinical records were reviewed to retrieve the clinical course, treatment methods, and clinical otologic complaints reported after the initial diagnosis of leukemia. We reviewed autopsy reports to determine the proportion of other organs with leukemic cells and then considered the histopathologic correlations of clinical findings.
3
Results
Nine patients (69.2%) had one or more otologic complaints according to the clinical reports ( Table 1 ). Hearing loss was the most common complaint. Sensorineural hearing loss was noted in 1 patient and conductive hearing loss in 1 patient, but the type of hearing loss was not clear in 3 patients. Four patients (30.8%) had no clinical otologic complaints. Six patients had otalgia, otorrhea, and/or ear bleeding. One patient had undergone surgery for acute mastoiditis, at which time ALL relapse was diagnosed. One patient had an ear tube inserted for exudative otitis media, and 4 other patients were treated conservatively for otitis externa and otitis media.
| Otologic complaints | No. (%) of patients |
|---|---|
| Hearing loss | 5 (38.5) |
| Otorrhea | 4 (30.8) |
| Otalgia | 4 (30.8) |
| None | 4 (30.8) |
| Vertigo | 2 (15.4) |
| Ear bleeding | 1 (7.7) |
The incidence of the histopathologic findings grouped according to their anatomic site in temporal bones of patients with ALL, is shown in Table 2 . Histopathologic findings of 9 patients (69.2%) were similar on both sides. Leukemic infiltration was observed most commonly in the marrow spaces of the petrous apex (13 patients, 24 temporal bones), including the marrow spaces of the ossicles (2 patients, 4 temporal bones) and the endochondral layer of the bony labyrinth (2 patients, 4 temporal bones). Leukemic infiltration was observed in the submucous membranes of the external auditory canal, tympanic membrane, middle ear, and mastoid. Infiltration was also observed inside and outside of the submucous vessels. Because of leukemic infiltration and congestion, the swelling of the external auditory canal was observed in 1 temporal bone, and that of the tympanic membrane in 5 temporal bones of 3 patients. Leukemic infiltration of the cochlea, vestibule, and internal auditory canal was observed in 4 temporal bones of 3 patients, 2 of whom complained of vertigo ( Fig. 1 ). Leukemic infiltration of the internal auditory canal was observed in the perineural and endoneural sheaths of the seventh and/or eighth cranial nerves. Leukemic cells were observed in the cerebrospinal fluid (CSF) of 3 patients with leukemic infiltration of the internal auditory canal, one of whom had severe sensorineural hearing loss in both ears ( Fig. 2 ). Although leukemic infiltration of the facial canal was observed, none of these cases had exhibited facial paralysis. All patients had leukemic infiltration in some areas of temporal bones.
| Area | Leukemic infiltration | Hemorrhage | Inflammatory changes | |||
|---|---|---|---|---|---|---|
| No. (%) of patients (n = 13) | No. (%) of TBs (n = 25) | No. (%) of patients (n = 13) | No. (%) of TBs (n = 25) | No. (%) of patients (n = 13) | No. (%) of TBs (n = 25) | |
| External ear | 4 (30.8) | 7 (28.0) | 1 (7.7) | 2 (8.0) | 0 | 0 |
| TM | 6 (46.2) | 8 (32.0) | 1 (7.7) | 2 (8.0) | 1 (7.7) | 1 (4.0) |
| Middle ear | 7 (53.8) | 14 (56.0) | 6 (46.2) | 9 (36.0) | 4 (30.8) | 5 (20.0) |
| Mastoid | 6 (46.2) | 10 (40.0) | 4 (30.8) | 5 (20.0) | 2 (15.4) | 2 (8.0) |
| Cochlea | 3 (23.1) | 4 (16.0) | 4 (30.8) | 4 (16.0) | 5 (38.5) | 8 (32.0) |
| Vestibule | 3 (23.1) | 4 (16.0) | 6 (46.2) | 6 (24.0) | 5 (38.5) | 8 (32.0) |
| Modiolus | 2 (15.4) | 3 (12.0) | 1 (7.7) | 1 (4.0) | 0 | 0 |
| Facial nerve | 4 (30.8) | 7 (28.0) | 2 (15.4) | 3 (12.0) | 0 | 0 |
| IAC | 5 (38.5) | 8 (32.0) | 6 (46.2) | 7 (28.0) | 0 | 0 |
| Petrous apex | 13 (100 ) | 24 (96.0) | 1 (7.7) | 1 (4.0) | 0 | 0 |
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