|Year : 2016 | Volume
| Issue : 4 | Page : 250-254
A Study of metastasis to brain with emphasis on rare tumors and role of immunohistochemistry
Rajani Mutyala, Maruthi D Karri, Sailabala Garikaparthi, Padmavathi D Chaganti
Department of Pathology, Guntur Medical College, Guntur, Andhra Pradesh, India
|Date of Web Publication||23-Dec-2016|
Department of Pathology, Guntur Medical College, Guntur, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Introduction: Secondary involvement of the central nervous system (CNS) by direct extention or hematogenous metastasis is a common complication of systemic cancer. Adenocarcinoma was the most common metastatic deposit in the present study, along with a few rare cases such as metastasis from hepatoblastoma, follicular variant of papillary carcinoma, and germ cell tumor of the testis.
Aim: This study was undertaken to know the incidence of secondary deposits in the brain. Age, sex, location in the brain, and type of malignancy were studied. In rare cases, immunohistochemistry was done to assess the exact histopathological confirmation.
Material and Methods: This study was carried out on a retrospective basis in our institution from March 2012 to July 2015. During the 3 year period, a total of 33 metastatic tumors were diagnosed based on hematoxylin and eosin stained sections of formalin-fixed and paraffin-embedded biopsy specimens.
Results: Out of 33 metastatic deposits, adenocarcinoma was the most common secondary deposit in the CNS. In addition, we encountered metastatic deposit from the follicular variant of papillary carcinoma, germ cell tumor from the testis, and hepatoblastoma. Immunohistochemical study was done in a selective cases.
Conclusion: This study highlights rare metastatic deposits in the CNS.
Keywords: CNS tumors, germ cell tumor, hepatoblastoma, immunohistochemistry, metastasis
|How to cite this article:|
Mutyala R, Karri MD, Garikaparthi S, Chaganti PD. A Study of metastasis to brain with emphasis on rare tumors and role of immunohistochemistry. J NTR Univ Health Sci 2016;5:250-4
|How to cite this URL:|
Mutyala R, Karri MD, Garikaparthi S, Chaganti PD. A Study of metastasis to brain with emphasis on rare tumors and role of immunohistochemistry. J NTR Univ Health Sci [serial online] 2016 [cited 2020 Apr 5];5:250-4. Available from: http://www.jdrntruhs.org/text.asp?2016/5/4/250/196557
| Introduction|| |
Brain metastases vastly outnumber primary brain tumors.  Metastases from lung cancer, breast cancer, and melanoma account for a majority of brain metastases.  Brain metastases significantly contribute to the morbidity and mortality of patients despite the reputation of the brain to be a site with a very low rate of metastases. 
| Material and Methods|| |
All the cases diagnosed histologically as secondary central nervous system (CNS) tumors were retrieved from March 2012 to July 2015 from the departmental records. Routine hematoxylin and eosin stained sections of formalin-fixed paraffin-embedded tissues were reviewed in all cases. Immunohistochemical (IHC) markers HMB-45, glial fibrillary acidic protein (GFAP), and cytokeratins were used in those tumors where the differential diagnoses were between primary tumor of glial origin and metastases; markers such as synaptophysin and chromogranin were used to demonstrate neuroendocrine differentiation. CD45 was used to confirm lymphoma.
| Results|| |
In the study period, 33 secondary CNS tumors were encountered. Overall, adenocarcinomas accounted for a maximum number of cases (60.60%) followed by squamous cell carcinoma (12.12%), adenosquamous carcinoma (3.03%), follicular variant of papillary carcinoma (FVPTC) (6.06%), malignant melanoma (3.03%), neuroendocrine carcinoma (6.06%), lymphoma (3.03%), germ cell tumor (3.03%), and hepatoblastoma (3.03%) which was accounted rarely [Table 1]. Male: female ratio was 1:1% [Table 2]. Age group was wide ranging from 4 to 80 years [Table 3]. Majority of the cases were seen in the 4 th and 5 th decades. Most of the lesions were present in cerebral hemispheres, followed by carpus callosum and cerebellum.
| Discussion|| |
The most common mass lesions in the brain are metastatic tumors. Brain metastases commonly originates from systemic cancers of the lung, breast, skin, and colorectum.  Lung tumors account for 50% of all metastatic brain tumors. ,, Metastases to cerebellum usually originates from colorectal, uterine, and renal carcinomas. ,, Whereas spinal epidural metastases most commonly originates from the prostrate, breast, lung, and kidney.  Metastases usually manifest as late symptoms of a primary tumor. Nevertheless, they may occur when systemic disease is still not apparent. ,, The route of metastases to CNS may be both by hematogenous dissemination and by direct extension of primary solid tumors. ,,,,
In the present study, it was found that cerebral hemispheres were the most common locations followed by the cerebellum. This finding is in accordance with the literature. ,,
In concordance with literature, we also encountered maximum number of adenocarcinoma cases followed by squamous cell carcinomatous metastasis. Six cases of adenocarcinoma with unknown primary [Figure 1], 7 cases from breast carcinoma, 5 cases from lung adenocarcinoma, 2 cases from colon, 2 cases from lung squamous cell carcinoma, 2 and cases from the skin. We also encountered two cases of the FVPTC. CNS metastases from FVPTC is very rare with a frequency of 0.1 to 5.1. ,, Left frontal region swelling with protrusion of eyeball in a 55-year-old woman was diagnosed as metastases from FVPTC. Another case was of a female aged 67 years with swelling on the frontal region [Figure 2]a. On histopathological examination, the tumor was composed of thyroid follicles of variable sizes filled with colloid. Cells showed nuclear crowding, ground glass nucleus, and nuclear grooving [Figure 2]c. Bone destruction was also seen [Figure 2]b.
|Figure 2: (a) Computed tomography of the brain intensely enhancing lesion involving the left frontal lobe with bone destruction and extracranial extension. (b) Follicular variant of papillary carcinoma 10× tumor with bone destruction. (c) Follicular variant of papillary carcinoma 40× showing nuclear grooving|
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In addition, we had 2 cases of investigation of neuroendocrine carcinoma sections that showed uniform cells with scant pink granular cytoplasm and round-to-oval stippled nucleus cells arranged in glands, islands and nests. There was minimal pleomorphism, confirmed by IHC markers synaptophysin and chromogranin.
In the present study, we also encountered adenosquamous carcinoma, malignant melanoma, and lymphoma [Figure 4]. In one case, a mass lesion presented in the corpus callosum in an 80-year-old woman. The differential diagnoses were malignant melanoma and pigmented ependymoma; strong positivity was expressed for HMB-45 whereas GFAP was negative, thus clinching the diagnosis of a metastases from malignant melanoma [Figure 3]. In one case, differential diagnoses included metastatic carcinoma and glioblastoma; strong positivity for PanCK was demonstrated while GFAP was negative, e supporting the diagnosis of metastasis. Primary site could not be analyzed.
|Figure 4: non-Hodgkin lymphoma deposit 40× and inset showing CD45 positivity|
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Brain metastases from germ cell tumor has been reported to be rare, occurring in approximately 2% of testicular germ cell tumors. 
We also encountered one case of germ cell tumor metastases to brain in a 31-year-old male who after orchidectomy and radiotherapy for the same later presented with headache, nausea, and vomiting. Magnetic resonance imaging of the brain revealed right parietal lobe lesion. Histopathological examination revealed uniform cells with clear cytoplasm and large central nucleus with lymphocytes infiltrating fibrous septa [Figure 5]. Metastatic mixed germ cell tumor in CNS is very uncommon. ,
|Figure 5: Metastases from germ cell tumor 40× uniform cells with clear cytoplasm, large central nucleus, and lymphocytes infiltrating fibrous septa|
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Brain metastases from hepatoblastoma is an extremely rare occurrence with only a few such reported cases.  A 4-year-old male child presented with frontal headache and vomiting with a past history of hepatoblastoma at the age of 5 months. Biopsy was done and histopathological examination revealed round-to-oval cells with abundant cytoplasm arranged in trabecular and few in an acinar pattern [Figure 6].
|Figure 6: Metastases from hepatoblastoma 40× acinar, sinusoidal pattern; cells with abundant cytoplasm|
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Brain metastasis is rare in children with hepatoblastoma;  most common site for metastases is lung.
Begemann et al. have reported a case of 12-month-old male child who presented with a large liver mass and pulmonary nodule. 
According to the literature, metastases of unknown primary origin account for approximately 3% of the cases.  Because of these reasons, IHC diagnosis of such cases is essential.
| Conclusion|| |
Secondary involvement of CNS either by direct extension or hematogenous metastasis is a common complication of systemic cancer. In our study, we encountered rare metastatic deposits in brain. It is difficult to determine the primary site of metastatic tumors even on histopathological examination. The IHC plays an important role in such problematic cases.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 4], [Figure 5], [Figure 6]
[Figure 2], [Figure 3], [Table 1], [Table 2], [Table 3]