To the Editor:
Non-Hodgkin lymphoma represents about 4.3% of all new cancer cases in the US annually.
1Of the many subtypes of non-Hodgkin lymphoma, small lymphocytic lymphoma/chronic lymphocytic leukemia comprises 18.3% and presents primarily with asymptomatic lymphadenopathy or abnormal complete blood count, or both. Central nervous system involvement with small lymphocytic lymphoma is rare.
- Chiu B.C.
- Hou N.
Epidemiology and etiology of non-hodgkin lymphoma.
Cancer Treat Res. 2015; 165: 1-25
The objective of this study was to report a case of small lymphocytic lymphoma presenting with hypopituitarism due to sellar involvement.
A 71-year-old white man presented with fatigue, cold intolerance, and decreased alertness. The patient denied headache or visual changes. Physical examination was unremarkable, including normal visual fields. Laboratory studies revealed low thyroid-stimulating hormone (0.407) with low free T4 (0.034 ng/dL), indicating secondary hypothyroidism. Additional studies showed low testosterone (<3 ng/dL) and a depressed morning cortisol level (5.3 μg/dL). Contrast-enhanced T1-weighted magnetic resonance imaging of the brain revealed a 1.1 × 1.8 × 1.1-cm enhancing suprasellar mass, consistent with macroadenoma, abutting the optic chiasm without displacement (Figure). Transsphenoidal resection of the pituitary mass revealed small lymphocytic lymphoma. Bone marrow biopsy confirmed disease involvement from small lymphocytic lymphoma with 10%-20% involvement. The patient received radiation therapy to the pituitary using an involved site technique with 24 Gy given in 1.8- to 2-Gy fractions. Radiation was well tolerated and the patient is being monitored in follow-up with physical examinations, complete blood counts, and serial magnetic resonance imaging. Systemic therapy is being reserved for disease progression in this patient, who is currently asymptomatic.
Treatment of lymphoma involving the central nervous system is challenging due to the various degrees of difficulty for some drugs to cross the blood–brain barrier, resulting in sub-therapeutic concentrations of the medications in the cerebrospinal fluid. Medications such as methotrexate, when administered intravenously at high doses, can achieve therapeutic levels in the cerebrospinal fluid. Rituximab has also been used successfully in central nervous system lymphoma regimens for CD20+ lymphomas. Therapeutic challenges in this patient included a low mitotic rate and a low percentage of CD20 expression, which would be anticipated to limit the efficacy of CD20-targeted immunotherapy. Furthermore, given the indolent nature of small lymphocytic lymphoma and the localized, low disease burden in this patient, aggressive systemic therapy could be considered overtreatment. Given the radiosensitive nature of this histology, low to moderate doses of 20-24 Gy can achieve excellent tumor control with minimal long-term toxicity.
The therapeutic goal was local control. When administering radiation therapy to the pituitary region, dose-limiting toxicities include the proximity to the optic chiasm, with risk of visual loss occurring with doses above 45 Gy.
2A second consideration is permanent panhypopituitarism. The most sensitive pituitary hormone is growth hormone, with dysfunction seen after 20 Gy.
- Roden D.
- Bosley T.M.
- Fowble B.
- et al.
Delayed radiation injury to the retrobulbar optic nerves and chiasm. Clinical syndrome and treatment with hyperbaric oxygen and corticosteroids.
Ophthalmology. 1990; 97: 346-351
3Anterior pituitary hormones are more radiosensitive at doses of 30 Gy or higher, and the majority of patients present with the typical temporal sequence of pituitary failure—growth hormone deficiency, gonadotropin deficiency, adrenocorticotropic hormone deficiency, and lastly, with thyroid-stimulating hormone deficiency.
- Chemaitilly W.
- Li Z.
- Huang S.
- et al.
Anterior hypopituitarism in adult survivors of childhood cancers treated with cranial radiotherapy: a report from the St Jude Lifetime Cohort study.
J Clin Oncol. 2015; 33: 492-500
4However, radiation-induced hypopituitarism can present with any temporal sequence of hormonal deficiencies. The posterior pituitary is a more radio-resistant tissue, with only rare episodes of diabetes insipidus observed.
- Appelman-Dijkstra N.M.
- Kokshoorn N.E.
- Dekkers O.M.
- et al.
Pituitary dysfunction in adult patients after cranial radiotherapy: systematic review and meta-analysis.
J Clin Endocrinol Metab. 2011; 96: 2330-2340
With regard to radiation dosimetry, there was a question as to the therapeutic efficacy of various radiation doses for the treatment of small lymphocytic lymphoma. This patient was successfully treated with radiation therapy to a total dose of 24 Gy and achieved complete radiographic resolution of the pituitary. He remains alive and asymptomatic with marrow-only involvement by small lymphocytic lymphoma 18 months after radiation therapy. The patient remains on levothyroxine, hydrocortisone, and testosterone replacement therapy. This case illustrates a rarely described presentation of a patient with small lymphocytic lymphoma manifesting as hypopituitarism. To the best of our knowledge, this represents only the fourth such case described.
- Krisht K.M.
- Palmer C.A.
- Couldwell W.T.
Combined chronic lymphocytic leukemia and prolactinoma: a rare occurrence in a patient presenting with pituitary apoplexy.
J Neurosurg. 2013; 119: 924-928
- Epidemiology and etiology of non-hodgkin lymphoma.Cancer Treat Res. 2015; 165: 1-25
- Delayed radiation injury to the retrobulbar optic nerves and chiasm. Clinical syndrome and treatment with hyperbaric oxygen and corticosteroids.Ophthalmology. 1990; 97: 346-351
- Anterior hypopituitarism in adult survivors of childhood cancers treated with cranial radiotherapy: a report from the St Jude Lifetime Cohort study.J Clin Oncol. 2015; 33: 492-500
- Pituitary dysfunction in adult patients after cranial radiotherapy: systematic review and meta-analysis.J Clin Endocrinol Metab. 2011; 96: 2330-2340
- Combined chronic lymphocytic leukemia and prolactinoma: a rare occurrence in a patient presenting with pituitary apoplexy.J Neurosurg. 2013; 119: 924-928
Published online: September 05, 2015
Conflict of Interest: None for all authors.
Authorship: All authors had access to the data and played a role in writing the manuscript.
© 2016 Elsevier Inc. Published by Elsevier Inc. All rights reserved.