Sir,We read with interest the case report “Primary adrenal lymphoma: Differential involvement with varying adrenal function” recently published in your journal in the July-September issue.[1] The authors have presented a good and exhaustive literature review on the topic, but have not discussed the origin of lymphoma primarily from the adrenals.We would like to highlight the fact that the occurrence of lymphoma primarily in the adrenal glands without involvement of any other lymphoid tissue in the body remains an enigma as the normal adrenal in humans is devoid of any lymphoid or hematopoietic tissue.[2] Proposed hypotheses for the occurrence of primary adrenal lymphoma include pre-existing autoimmune adrenalitis with lymphocyte infiltration or occurrence of hematopoietic rest tissue in the adrenals, although not conclusively proven due to the rarity of the disease.[23] The follicular centre cell origin of primary adrenal lymphoma suggests that the tumor may have arisen on a background of previous autoimmune adrenalitis.[2] The occurrence of primary adrenal lymphoma in a setting of pre-existing autoimmune adrenalitis is analogous to the occurrence of primary lymphoma in the thyroid on a background of autoimmune Hashimoto's thyroiditis, as lymphatic tissue is absent in the normal thyroid tissue also.The authors have discussed the occurrence of variable adrenal insufficiency in primary adrenal lymphoma on the basis of the extent of adrenal tissue involvement, with bilateral disease developing primary adrenal insufficiency and unilateral disease having normal adrenal function.[1] Adrenal insufficiency in patients with bilateral adrenal metastasis is rare (1%)[4] and develops only when >90% of the adrenal tissue is infiltrated.[5] In contrast, a very high frequency of primary adrenal insufficiency (60%-70%) has been reported in patients with primary adrenal lymphomas, including patients with mildly enlarged adrenals also.[25] We would like to add that an additional mechanism that could explain the higher occurrence of primary adrenal insufficiency in patients with primary adrenal lymphoma as opposed to the rare occurrence in adrenal metastasis is the possibility of pre-existing autoimmune adrenalitis in patients with primary adrenal lymphoma.[2]