Schwannoma is a benign, usually encapsulated, nerve sheath tumour originating from Schwann cells. Primary schwannomas of the adrenal gland are extremely rare.Case report
We present a case of 55 year old female patient with breast cancer, treated with mastectomy and lymphadenectomy with subsequent hormonal therapy. Three months after mastectomy, ultrasonography revealed a hormonally inactive tumour in the left adrenal gland which was suspected to be a metastasis. Adrenalectomy was performed and the microscopic and immunohistochemical examinations revealed the tumour to be a schwannoma.Conclusion
As adrenal schwannomas are so infrequent, they can pose diagnostic problems and should be differentiated from other spindle cell lesions of the adrenal gland or metastatic tumours.
El schwannoma es un tumor benigno, encapsulado, de la vaina de mielina, originándose en las células de Schwann. El schwannoma primario de la glándula suprarrenal es muy infrecuente.Caso clínico
Se presenta un caso de una paciente de 55 años, diagnosticada de cáncer de mama y tratada con mastectomía, linfadenectomía y terapia hormonal. Tres meses tras la mastectomía se detectó ecográficamente un tumor, sin actividad hormonal, en la glándula suprarrenal izquierda. Se sospechó una metástasis y se realizó una adrenalectomía. La histología e inmunohistoquímica del tumor fueron consistentes con schwannoma.Conclusión
Debido a la poca frecuencia del schwannoma suprarrenal pueden ocurrir problemas diagnósticos y deben diferenciarse de otras lesiones de células de la glándula suprarrenal o de tumores metastásicos.
Schwannoma is a benign nerve sheath tumor originating from Schwann cells, occurring within neurofibromatosis type 2. Sporadic schwannomas are associated with mutations in the NF2 gene on chromosome 22 and are almost always solitary. Schwannomas can occur at any age but are most common between 20 and 50 years, with no sex predilection1. Grossly, they are well-circumscribed, usually encapsulated masses that are attached to the nerve but can be separated from it. Clinically, schwannomas present as painless, slowly growing mass without neurological symptoms, unless the tumor becomes large. Predilection sites are the head and neck region and the flexor surfaces of the extremities. Within the cranial vault, they are most commonly found in the cerebellopontine angle, attached to the vestibular branch of the eighth nerve. Schwannomas can rarely develop in viscera (reported in heart, kidney, lung, gastrointestinal tract, liver, pancreas), retroperitoneum, or any other part of the body2–5.
Except in cases of von Recklinghausen's disease, the adrenal localization of schwannoma is particularly rare.Case report
We present a case of 55 year old female patient with previously diagnosed breast cancer that was treated with mastectomy followed by lymphadenectomy. Histologically, breast cancer was classified as ductal invasive breast carcinoma, histological grade 2 (Figure 1), without lymph node metastases. Immunohistochemical reaction to estrogen and progesterone was positive in more than 75% of tumor cells (according to ASCO/CAP 2010 recommendations, hormonal receptors are considered positive if ≥1% of tumor cell nuclei are immunoreactive). Tumor cells showed negative (0) reaction to HER2/neu. Proliferative rate measured immunohistochemically with Ki-67 was 12% at most. There were no signs of neurofibromatosis on clinical examination.
Patient was treated with hormonal therapy. Three months after mastectomy ultrasound examination revealed hormonally inactive tumor in the left adrenal gland that was suspected for a metastatic process. Adrenalectomy was performed and macroscopic examination of the specimen showed partially encapsulated tumor within the adrenal gland with yellowish, solid cut surface, measuring 5×4×3cm (Figure 2A). The resected tissue was formalin fixed, paraffin embedded, cut at 5μm and routinely stained with hematoxylin and eosin. Microscopically, tumor was composed of solid sheets and bundles of uniform spindle shaped cells, along with various vascular and inflammatory elements embedded in an abundant extracellular matrix (Figure 2B). No Verocay bodies were found. Extensive histological analysis revealed no ganglion cells. Immunohistochemically, tumor cells stained positive for S-100 protein (Figure 2C), vimentin (Figure 2D) and glial fibrillary acidic protein (GFAP) (Figure 2E). Proliferative rate measured immunohistochemically with Ki-67 was 5% at most, being considerably lower than the one measured in primary breast carcinoma (12%). Histological and immunohistochemical analyses of described adrenal gland tumor were consistent with the diagnosis of schwannoma.
At present, five years after initial diagnosis, the patient is well and without recurrence of breast cancer or adrenal schwannoma.Discussion
Adrenal tumors are frequently discovered as an incidental finding during a workup for some other disease, making their therapy often a subject of controversial discussion. According to recent studies, patients with a non-functional adrenal incidentaloma exceeding 4cm in diameter (3cm by some authors), should be considered for surgery, although the size of the tumor should not be the sole criterion6–8. Combination of magnetic resonance imaging and fine-needle aspiration cytology should be considered the strategy of choice with the aim of selecting patients for surgery8. The clinical criterion for surgically treating our patient was a suspicion that the adrenal mass detected by ultrasound was a metastasis from invasive ductal carcinoma, for which the patient had previously been surgically and hormonally treated. The PET study or the combination of magnetic resonance imaging and fine-needle aspiration cytology weren’t performed.
The large majority of neoplasms of the adrenal gland originate from constituent cortical, chromaffin, or neuronal cells. Nerve sheath tumors of the adrenal gland are rare and include schwannoma, neurofibroma1 and malignant peripheral nerve sheath tumor2,6,9. According to our knowledge, there are only a few well-documented cases of schwannoma originating from adrenal gland in English literature2,9–12. Patients usually present with upper abdominal pain and symptoms secondary to the mass effect of the tumor, although 2 clinically asymptomatic cases of adrenal schwannoma have been documented as incidental findings during autopsy2.
Grossly, adrenal schwannomas are usually solitary, well delineated tumors, sometimes surrounded by fibrous capsule, that have a solid cut surface9. Larger tumors may have secondary degenerative changes such as cystification and calcification1,9. Schwannomas of the adrenal gland are grossly and histologically identical to schwannomas found at other sites1,9. Both classical and cellular variants may be observed. Conventional schwannoma is composed of spindle cells with alternating compact, hypercellular Antoni A areas and loosely textured, hypocellular Antoni B areas, Verocay bodies and thick-walled, hyalinized blood vessels1,9. The cellular variant is usually showing higher cellularity with a largely Antoni A pattern, an absence of well-formed Verocay bodies and sparse mitotic activity. The presence of varying degrees of inflammation has been previously observed in schwannomas of the adrenal gland2,9, as well those of other sites1.
Immunohistochemically, schwannomas characteristically exhibit strong and diffuse positivity for S-100 protein and also typically display pericellular reactivity for collagen IV.
The microscopic appearance of conventional schwannoma is quite distinctive for the diagnosis to be made on routine histological sections. The diagnosis can easily be confirmed with the use of immunohistochemistry for S-100 protein1,9,10. The differential diagnosis of adrenal gland schwannoma depends upon whether the tumor shows a classic or cellular histology. The main difficulty in setting of a right diagnosis is actually the unusual anatomic location of the tumor, rather than its morphologic appearance9.
The differential diagnosis of cellular schwannoma includes various neoplasms of the adrenal gland that are composed of spindle cells. Pheochromocytomas may consist predominantly of spindle cells, but are uniformly positive for chromogranin and synaptophysin, and negative for S-100 protein. Also, pheochromocytomas are hormonally active tumors, so schwannoma can readily be excluded on the basis of positive urinary metanephrines.
Neurofibromas may be indistinguishable from schwannomas, due to similar microscopic appearance and positivity for S-100 protein, although neurofibromas tend to variably express S-100 and aren’t encapsulated. Fine et al13 distinguish them by using calretinin which is expressed in schwannoma but not in neurofibroma. Ganglioneuroma, also a neoplasm composed of spindle-shaped cells, may often have areas lacking the ganglion cell component. Therefore, adequate sampling is necessary to identify ganglion cells which will serve to differentiate ganglioneuroma from adrenal gland schwannoma. The differential diagnosis of cellular schwanomma includes also rare spindle cell mesenchymal tumors like leiomyoma and solitary fibrous tumor.
Immunohistochemically, leiomyomas are positive for desmin and smooth muscle actin, which is not the case in cellular schwannomas. Solitary fibrous tumors is strongly positive for CD34 and negative for S-100 protein and also lacks the uniform cellularity of cellular schwannoma.
In summary, similar to schwannoma of other sites, adrenal schwannomas appear to behave in a benign fashion. In most instances the diagnosis can be made on histologic and immunohistochemical grounds. The combination of adrenal gland schwannoma and primary breast cancer is very rare, probably incidental, but preoperatively difficult to distinguish from metastasis.Conflict of interest
The authors have no conflicts of interest to declare.