24‐Year‐Old Woman with Recent Onset Back Pain

Clinical History

A previously healthy 24‐year‐old white female patient presented to the emergency room with back pain. The pain, which had been ongoing for the past 4 days, started in her lower back and wrapped around her left leg down below the knee. It was constant and worsened with any activity. Bladder and bowel function were unaffected. The patient denied any prior history of back pain or back injury. She did not have any history of trauma. On physical examination, no focal neurological findings were noted.

An MRI was obtained, which demonstrated a prominent lesion within the spinal canal that showed relative homogeneous enhancement (Figure 1A). L2‐L3 laminectomies were performed and all visible tumor was removed with only microscopic residual near the conus.

Figure 1.

Microscopic Pathology

Multiple irregular tan fragments of soft tissue measuring in aggregate 5 × 5 × 1.8 cm were submitted for pathological examination. The formalin‐fixed biopsy samples were processed with standard technique and stained routinely with H&E as well as with antibodies against cytokeratin (CAM5.2), EMA, progesterone receptor, GFAP, S‐100 protein, synaptophysin, chromogranin, inhibin and Melan‐A. The tumor was composed of monomorphous polygonal cells without a distinct growth pattern (Figure 1B). Cytologically, the tumor cells contained round, relatively uniform nuclei with small central nucleoli. While most of the cells contained granular slightly eosinophilic cytoplasm (Figure 1C), some cells showed a fine peripheral clear vacuolation, at times, confluent throughout the cytoplasm imparting a pale appearance. Focal intracellular yellowish pigment was noted in some cells. Only rare mitotic figures were identified. No invasive features or tumor necrosis were identified. All cells showed strong positivity for inhibin (Figure 1D) and Melan‐A (Figure 1E), while weak to moderate reactivity was seen with synaptophysin in over 50% of tumor. Immunostains for S100 protein, CAM5.2, EMA, progesterone receptor (PR), chromogranin, and TTF‐1 were negative. Ki‐67 labeling index was low (<2%).

Formalin‐fixed paraffin‐embedded tumor was reprocessed for ultrastructural studies. Clusters of polygonal cells with abundant cytoplasm and regularly shaped nuclei as well as dispersed chromatinwere present. The cytoplasm contained abundant smooth endoplasmic reticulum (Figure 1F) and mitochondria with tubulovesicular cristae (Figure 1G). Occasional dense core secretory granules were present. Intercellular junctions were scant and poorly formed. What is your diagnosis?

Diagnosis

Ectopic adrenal cortical adenoma

Discussion

The typical differential diagnosis of patients presenting with an intradural cauda equina mass includes myxopapillary ependymoma (WHO grade I) arising from the filum (much less frequently a classic ependymoma), paraganglioma, a tumor also arising from the filum terminale, and benign nerve sheath tumors, in particular schwannoma, arising from the nerve roots. Less frequently, meningioma, especially the rare clear cell variant, can present as cauda equina mass. Other tumors, including peripheral PNETs, can arise in the filum, but they are extremely rare. Metastases to the conus medullaris and cauda equina are exceptional. In our case, the adrenocortical nature of the tumor was suspected once the more common diagnoses of ependymoma and meningioma, possibly with oncocytic features, were excluded by the completely negative S100 protein, EMA, and PR immunohistochemical stains (these last two stains repeated in two different laboratories). Despite the presence of synaptophysin positivity, the lack of nesting (Zellballen) architecture and the abundant pale and finely granular cytoplasm of the tumor cells seemed very unusual for the diagnosis of paraganglioma. Once the possibility of adrenal cortical tissue was considered, we obtained Melan‐A and inhibin which, coupled with synaptophysin, confirmed the diagnosis. The immunophenotype with Melan‐A, inhibin, and synaptophysin positivity is unique to adrenal cortical neoplasms. The ultrastructural findings with abundant smooth endoplasmic reticulum, mitochondria with tubulovesicular cristae, and scant dense core granules are also very characteristic. Despite the very bland and histologically benign appearance of the tumor, given the rarity of the lesion, it was suggested to exclude clinically the possibility of a metastatic carcinoma originating in the adrenal glands. Occurrence of ectopic adrenal tissue (cortex and medulla or cortex alone) has been reported in a variety of anatomical sites, including the central nervous system (CNS) 4. Adrenocortical tumors, both benign and malignant, presumably arising from ectopic adrenocortical rests, have also been reported in the CNS, where they seem to have a predilection of the lower spinal region, either in the cord or the cauda equina. Clinicopathologic features of reported cases were nicely summarized in table form by Rodriguez et al. 3. Ectopic adrenal tissue is commonly found in the upper abdomen or along the path of gonadal descent with which the adrenal gland is closely associated during development. It is not clear why ectopic adrenal tissue would occur outside this area and, in particular, in the lower spinal cord region. Karikari et al. found the adrenal cortical tumor, located in the conus, to be associated with a tethered cord and “cord lipoma,” which led them to speculate that the premature separation of ectoderm from neuroectoderm, before neurulation was completed, may have allowed invasion of the neural groove by mesodermal tissue committed to the formation of adrenocortical tissue1. The possibility that retroperitoneal adrenal rests may gain intradural access along the exiting nerves or entering vessels has been suggested for those tumors, which do not occur in association with dysraphism2. Most reported cases of ectopic adrenal cortical tumors are benign and have behaved in an indolent fashion. In a case we previously reported, due to the presence of mitotic activity, we originally made a cautious diagnosis of adrenocortical tumor of indeterminate malignant potential. The pathologic, molecular, and clinical features of this tumor, including its prompt recurrence after a gross total resection, suggested a low‐grade carcinoma. The patient received chemotherapy and is now well without evidence of recurrence. Ectopic adrenocortical tumors both benign and clinically aggressive may occur in the CNS and, in particular, in the distal spinal region. Although they are rare, pathologists should be aware of them and consider this possibility.