A 69‐Year‐Old Woman with an Epidural Mass

Clinical History

A 69‐year‐old woman presented with a 2‐month history of progressive bilateral leg weakness and gait difficulty. On examination, the patient had diffuse lower extremity weakness and hypesthesia of the left leg. Magnetic resonance imaging revealed a 2.9‐cm, extradural, soft tissue mass at the T5–6 level, with spinal cord compression; the mass was hypointense on a T1‐weighted image (Figure 1a) and hyperintense on a T2‐weighted image (Figure 1b). The tumor was a relatively well‐demarcated epidural mass with focal invasions into both facet joints. Intraoperative examination showed a neoplasm with clear and granular cell morphologies displaying solid, papillocystic, and follicular patterns. Postoperative 18F‐fluoro‐2‐deoxy‐d‐glucose positron emission tomography‐computed tomography (CT) and neck CT failed to identify a primary tumor or any other lesions.

Figure 1.

 

Microscopic Pathology

Histologically, the tumor showed various histologic patterns consisting of round to polygonal cells with abundant cytoplasm and small, round, uniform nuclei. The predominant growth pattern was solid with sheets or nests separated by fibrovascular stroma (Figure 1c). Some tumor cells formed papillary folds interspersed with cystic spaces, forming a so‐called “papillocystic” pattern (Figure 1d). Further, there were epithelial‐lined cystic spaces filled with eosinophilic, proteinaceous materials, resembling thyroid follicles (Figure 1e). Most of the tumor cells had abundant, clear, vacuolated cytoplasm with distinct cell borders. In addition, nests of granular cells with abundant basophilic to amphophilic, fine to coarse granules were mixed with more eosinophilic ductal cells, forming microcysts (Figure 1f). The cytoplasmic granules were periodic acid‐Schiff (PAS)‐positive and diastase resistant. Neither whorl formation nor psammoma bodies were seen. Tumor necrosis was absent, and mitotic figures were rare. Immunohistochemically, the tumor cells were positive for cytokeratin AE1/AE3 (Figure 1g) and alpha‐1‐antitripsin (Figure 1h) and negative for S‐100 protein, CD10, thyroid transcription factor‐1 (TTF‐1), gross cystic disease fluid protein‐15 (GCDFP‐15), vimentin, and synaptophysin. What is the diagnosis?

Diagnosis

Metastatic acinic cell carcinoma.

Seventeen years earlier, in 1996, the patient had undergone resection of a mass on the right parotid gland at another hospital. The mass was completely resected, and neither local recurrence nor metastasis was found before the current manifestation. We confirmed that the pathological diagnosis was well‐differentiated acinic cell carcinoma.

Discussion

Acinic cell carcinoma (ACC) is a rare malignant neoplasm of the salivary gland that accounts for approximately 1–6% of all salivary gland neoplasms. Tumors recur in approximately 35% of cases, and metastasis is observed in up to 15% of cases 1, 4. High tumor stage, incomplete resection, and poor histological differentiation or dedifferentiation are often associated with more aggressive behaviors 2. The most common metastatic sites include the cervical lymph nodes, lung, liver, and bones 1, 4. Zook et al reported a case of solitary metastasis of dedifferentiated ACC in the L4 vertebral body, which developed 15 months after initial presentation 8. In another case reported by Vidyadhara et al, a bone‐destructive mass in the T4 vertebral body was detected 4 months after primary tumor resection; widespread metastases to regional lymph nodes and both lungs were simultaneously detected 6. Most recurrent or metastatic lesions appear within 5 years of treatment; this case is highly unusual given that the patient's initial diagnosis was made 17 years earlier and that no metastasis was noted at other sites. Late metastasis has been occasionally reported in cases of renal cell carcinoma, but rarely in cases of ACC. Two reports have described late metastasis of ACC to the skin and brain, both occurring 20 years after the initial diagnosis and showing well histological differentiation 5, 7. In contrast to cases showing early aggressive behavior, low‐grade ACC may have a propensity for late recurrence or metastasis. Thus, the possibility of metastatic ACC should be considered in the differential diagnosis of patients with a history of ACC, even if the initial diagnosis was made many years earlier.

Serous acinar differentiation of tumor cells is the morphologic hallmark of ACC, which is defined by the presence of PAS‐positive, diastase‐resistant, basophilic zymogen granules. However, in addition to the prototypical acinar cells, clear cells, intercalated duct cells, vacuolated cells, and nonspecific glandular cells are recognized within the same tumor. Furthermore, ACC may show various histologic patterns, as seen in this case: solid, microcystic, papillocystic, and follicular. These various histologic patterns and heterogeneous cellular composition can cause diagnostic difficulties, which become evident in tumors showing less obvious acinar cell differentiation. For the metastatic lesion, broader differential diagnoses should also be considered, e.g., when tumors predominantly consist of clear cells arranged in a solid pattern, clear cell renal cell carcinoma must be excluded by immunostaining for CD10 and appropriate clinical evaluation. For cases showing a frequent follicular pattern, immunostaining for antithyroglobulin or TTF‐1 is needed to differentiate thyroid follicular carcinomas. The papillocystic variant may be confused with carcinomas with papillary growth, such as papillary renal cell carcinoma or apocrine papillary carcinoma of the breast. Consideration of the primary tumor location and ancillary immunostaining can be helpful in the diagnosis. Recently, Skalova et al reported a new tumor entity “mammary analogue secretory carcinoma (MASC) of the salivary gland,” which has a growth pattern reminiscent of ACC and a predominance of intercalated duct‐like cells, but shows no true acinar cell differentiation 3. In short, the most important aspect in diagnosing ACC is the identification of acinar cell differentiation of the tumor cells.

We experienced great difficulties in the diagnosis of this metastatic ACC because of the various histologic patterns, scarcity of diagnostic acinar cells, and incomplete information about the patient's history. The clinician, in this case, was aware that the patient had undergone surgery for the earlier parotid gland tumor but ignored the possibility of metastasis because of the long disease‐free interval and did not report this fact. In summary, the identification of serous acinar differentiation is crucial for the diagnosis of metastatic ACC. Additionally, for patients with a previous history of ACC, irrespective of the time since the initial diagnosis, metastasis should be considered.