Isolated pineal gland metastasis of acute lymphocytic leukemia: case report

ABSTRACT

Metastasis in the pineal region is a rare condition. To best of our knowledge, there is no case report of isolated pineal metastasis secondary to acute lymphocytic leukemia (ALL). The aim of this study is to show the pineal gland involvement of ALL in a case for the first time in the literature. A 25-year-old male patient diagnosed with ALL 2 years ago presented with headache and visual impairment. Brain magnetic resonance imaging (MRI) revealed a well-defined solid lesion which was revealed intensive enhancement after contrast. On diffusion-weighted images, the lesion showed significant diffusion restriction. Three months after therapy, control MRI demonstrated a completely resorbed pineal lesion. The pineal region may be a possible site of metastasis and involvement due to the absence of a blood-brain barrier, and should not be overlooked in patients with not only solid cancers but also ALL.

Background

Pineal region tumors are rare and constitute approximately 1% of intracranial tumors in adults.¹ However, although metastasis is common in the brain, metastasis to the pineal region is very rare and constitutes 0.4–3.8% of all intracranial metastases.² Metastasis can be seen in the pineal region without metastasis elsewhere in the brain. Metastases in the pineal region are most commonly caused by lung cancer. The other tumors such as the esophagus, pancreas, kidney, stomach, colon, melanoma and myeloma are pineal metastasis reported in the literature.³ Acute lymphoblastic leukemia (ALL) is a heterogeneous disease with different subtypes showing typical clinical, biological and prognostic features. The incidence of the disease varies between 00.1–00.2% in the adult age group.⁴

To best of our knowledge, there is no case report of isolated pineal metastasis secondary to acute lymphocytic leukemia. The aim of this study is to show the pineal gland involvement of ALL in a case for the first time in the literature.

Case report

A 25-year-old male patient has presented with headache and visual impairment. When the patient’s records were examined, it was seen that he was diagnosed as T-cell ALL 2 years ago. In the medical records, it was understood that hyper-CVAD (Cyclophosphamide, Vincristine, Adriamycin, Dexamethasone) induction therapy was applied and the patient responded well to the treatment. However, it was found that the patient did not come to follow-up regularly after being in remission. Physical examination revealed deterioration in extraocular movements, upward paralysis, convergence, rotational nystagmus, and accommodation disorder. Laboratory findings revealed a mild normochromic normocytic anemia (hemoglobin = 11 g/dl, MCV = 85 fL, MCH = 30 pg) and mild leukocytosis (WBC = 12000/mm3). No blast cells were observed in the patient’s peripheral blood smear. Because the patient refused, the bone marrow biopsy could be not performed for diagnosis of the recurrence.

With these findings, intracranial involvement of ALL was considered clinically and brain magnetic resonance imaging (MRI) was performed. Brain MRI revealed a well defined solid lesion measuring approximately 1 cm in the pineal gland. Contrast-enhanced T1-weighted axial (Figure 1) image was revealed intensive enhancement of the lesion. On diffusion-weighted images (DWI), the lesion showed significant diffusion restriction, with reduced apparent diffusion coefficient (ADC) (Figure 2). Because of MRI findings, the patient underwent lumbar puncture and cerebrospinal fluid (CSF) sample was taken. The patient was diagnosed with central nervous system involvement of ALL due to the presence of multiple white blood cells (WBCs) on the CSF examination. Details of the CSF sample were as follows; elevated protein (155 mg/dl), decreased glucose (10 mg/dl) CSF concentration, increased leukemic blast count 30/µl, and increased WBC count (35/mm3). Because of positive CSF cell count and neuroradiological findings, flow cytometry on the CSF did not performed.

Figure 1.

Pre-contrast (a) T1-weighted axial MRI reveals a well defined solid lesion (frame) measuring approximately 1 cm in the pineal gland. Contrast-enhanced (b) T1-weighted axial image shows intensive enhancement (frame) of the lesion.

Figure 2.

DWI (a) shows significant diffusion restriction (frames) with reduced ADC (b) in the lesion.

Chemotherapy (intrathecal methotrexatea 15 mg once weekly and intrathecal cytarabinea 30 mg once weekly in the first month of consolidation therapy, thereafter intrathecal methotrexatea 15 mg once monthly and intrathecal cytarabinea 30 mg once monthly in the second and third months of consolidation therapy) was performed for metastatic leukemic infiltration. Three months after therapy, control MR imaging demonstrated a completely resorbed pineal lesion (Figure 3). The radiologic and clinic findings of the patient were consistent with the isolated pineal gland metastasis of acute lymphocytic leukemia. Clinical recovery of the ocular symptoms was complete within 3 months.

Figure 3.

On control MR imaging, T2-weighted sagittal (a) and pre- and post-contrast T1-weighted axial (a and c) images demonstrate a completely resorbed pineal lesion (arrows).

Discussion

In this case report, a patient with isolated ALL involvement in the pineal region is presented. Although the most common metastasis to the pineal region is lung cancer; metastasis from prostate, bladder, breast, esophagus, stomach, colon, melanoma, myeloma have also been reported in the literature.^3,5–7 Metastases are thought to be due to hematogenous spread due to lack of blood-brain barrier in the pineal region. Although pineal metastases are asymptomatic in most cases, headache, Perinaud’s syndrome and hydrocephalus may be seen.⁸ The pressure caused by the lesion on the posterior of the third ventricle and aqueduct causes obstructive hydrocephalus and intracranial pressure. Compression of the superior colliculus and posterior commissure leads to Perinaud’s syndrome, characterized by extraocular movement impairment, upward paralysis, convergence, rotational nystagmus, and accommodation disorder.⁹ Our patient also had headache and Perinaud syndrome clinically. In addition, leptomeningeal spread is common in patients. This is thought to be related to the neighborhood of the pineal gland with the cerebrospinal fluid pathways, the third ventricle, and the quadrigeminal cistern.⁸

The pineal gland is a small red-brown formation named after it because of its pinecone-like appearance. Its size is between 10–14 mm. It is located in the midline, above the tentorium and superior colliculi, below the splenium of the corpus callosum. It develops from the diverticulum in the diencephalic roof of the third ventricle in the second gestational month. The mature gland is suspended in the posterior ceiling of the third ventricle by the pineal stalk. Melatonin is released from the pineal gland to regulate the diurnal rhythm. The gland is histologically composed of lobules of pineocytes (95%), astrocytes (5%) and fibrous stroma separating them. Pineocyte is a specialized neuronal cell associated with retinal rod and cone. Concentric calcifications, also known as corpora arenacea, are seen from puberty. Since there is no blood-brain barrier in the pineal region, it shows significant enhancement in post-contrast series.²

Central nervous system (CNS) involvement of leukemia, which is defined by the presence of lymphoblasts in the cerebrospinal fluid, can be seen at the time of diagnosis or may occur as a relapse as in our patient. Isolated CNS relapse has been reported between 0–11% in different studies.^10,11 Although the definitive diagnosis is made by cerebrospinal fluid examination, imaging findings are also important in the diagnosis. MRI is the preferred method of imaging. MRI is useful in the diagnosis of enlargement or enhancement of cranial nerves, nodular or linear leptomeningeal enhancement extending to sulcus and basal cisterns. MRI may also exclude causes not associated with involvement such as bleeding and infarction.¹² In a study by Guenette et al.¹³ in patients with positive CSF cytology, the most common MRI finding was reported as pachymeningeal enhancement. In the same study, leptomeningeal enhancement, cranial nerve enhancement, masslike enhancement and spinal meningeal enhancement can be seen. Our patient had isolated pineal gland involvement without any of these findings. To best of our knowledge, there is no case report of isolated pineal gland involvement secondary to acute lymphocytic leukemia.

In conclusion, although rare, the pineal region may be a possible site of metastasis and involvement due to the absence of a blood-brain barrier, and should not be overlooked in patients with not only solid cancers but also ALL.

Disclosure of potential conflicts of interest

The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.