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Lymphocyte-Depleted Thymic Remnants
A Potential Diagnostic Pitfall in the Evaluation of Central Neck Dissections

Geoffrey A. Talmon MD, Jean E. Lewis MD
DOI: http://dx.doi.org/10.1309/AJCPB64YBYCGJEIM 707-712 First published online: 1 November 2009


The head and neck region is a frequent site for potentially confusing incidental benign findings not related to the primary pathologic process and having no impact on patient prognosis. Several lesions are thymic in origin. We report 3 cases of lymphocyte-poor thymic remnants identified in central cervical (level VI) lymph node dissections for unrelated benign and malignant pathology. In each, the rests were nearly completely composed of bland epithelial cells with rare admixed lymphocytes. These cells were immunophenotypically similar to thymic epithelial cells, although they differed in the paucity of associated thymic lymphocytes and lack of Hassall corpuscles. Lymphocyte-depleted thymic remnants in the central cervical compartment are not well described in the literature. It is important to be aware of these and other benign inclusions to avoid making incorrect diagnoses of malignancy.

Key Words:
  • Thymic
  • Cervical
  • Neck dissections
  • Benign

During the evaluation of malignancy, one may encounter unexpected abnormalities that are not related to the primary disease process. These anomalies are often benign and/or developmental and do not affect the ultimate prognosis of the patient in whom they are found. The challenge for pathologists is to be able to recognize these incidental findings and not mistake them for significant lesions.

The cervical region is embryologically dynamic. Many organs of branchial cleft origin, including the thyroid, thymus, and parathyroid glands, migrate through the area to their final normal anatomic locations. As such, there is the possibility of arrest of movement or the deposition of fragments of these structures in the cervical region during their travels.

We present 3 morphologically similar collections of benign thymic-like epithelium that were incidentally discovered in the central cervical compartment of patients undergoing neck surgery for unrelated pathology. These structures were predominantly composed of epithelial cells and devoid of associated thymocytes.1,2 Most “typical” thymic rests in the central cervical region (paratracheal, intratracheal, and intrathyroidal) are lymphocyte-rich.2 Although epithelial predominant variants are well recognized in the mediastinum,2 they are not well characterized in the head and neck region. We discuss the histologic appearance and immunoprofile of these collections of cells (that for the purposes of discussion we dub “central cervical epithelial rests” [CCERs]). It is our hope to raise surgeons’ and pathologists’ awareness of these benign structures that may cause diagnostic difficulty during the evaluation of neck dissection specimens.

Materials and Methods

Following approval by the Mayo Clinic Office of Human Research Protection Institutional Review (Rochester, MN), archived formalin-fixed, paraffin-embedded tissue was retrieved from the files of one of the authors (J.E.L.). H&E stains performed on 5-μm-thick sections were reviewed. Immunohistochemical studies were performed on the paraffin blocks containing the CCERs using the avidin-biotin complex technique. The following antibodies were used: cytokeratin (CK) cocktail (AE1/AE3), CK5/6, CK7, CAM 5.2, CK19, CK20, epithelial membrane antigen, smooth muscle actin, actin, calponin, p63, S-100, chromogranin, synaptophysin, thyroglobulin, thyroid transcription factor 1, parathyroid hormone, calcitonin, vimentin, CD34, CD10, androgen receptor, CD99, CD45, CD20, CD3, CD1a, and terminal deoxynucleotidyl transferase (TdT).


Clinical Findings

The clinical features of the 3 patients are summarized in Table 1 . Briefly, the patients ranged in age from 39 to 81 years. In each case, the patient presented with unrelated clinical findings. Two patients underwent surgery for papillary thyroid carcinoma. The third patient had hypercalcemia related to secondary hyperparathyroidism and underwent parathyroidectomy for multigland disease. No palpable or radiographic abnormality was identified in the locations in which the CCERs were found. However, in case 2, the CCER was detected microscopically at the time of frozen section, and the appearance of cords of epithelioid cells within fat raised the suspicion of a possible neoplastic process. No patient had a mediastinal mass, and thymic tissue was not grossly observed by the surgeon in the region of each CCER.

Pathologic Features

All CCERs were identified in tissue taken from the central cervical compartment. The epithelial rests were found in the region of the right tracheoesophageal groove, near the left inferior parathyroid gland, and in tissue submitted as central cervical compartment lymph nodes (level VI).

None were grossly detected; all were found incidentally within adipose tissue adjacent to lymph nodes or a parathyroid gland on microscopic examination. The rests ranged from less than 0.1 to 0.3 cm in greatest dimension.

The typical microscopic appearance of CCERs is illustrated in Image 1 . They were composed of collections of nondescript cuboidal to spindled epithelial cells arranged in cohesive clusters, nests, and cords that were intimately associated with the surrounding adipose tissue and occasionally cuffed capillary-sized blood vessels. Areas in case 2 showed rosette-like formations of cells without a central lumen or vessel. The epithelial cells had scant eosinophilic cytoplasm and round hyperchromatic nuclei. Rare, singly dispersed, small lymphocytes were present in each case. Keratinization, intercellular bridges, and distinct gland formation was absent. Hassall corpuscles were not identified. Mitotic figures were absent.

In case 3, a fragment of unremarkable involuted thymic tissue was present within the same paraffin block as the CCER Image 2 . The former displayed a larger population of small lymphocytes with well-developed Hassall corpuscles. The thymic epithelial cells (TECs) showed morphologic features similar to those in the CCERs but displayed prominent Hassall corpuscles.

Immunohistochemical Features

The immunophenotype of CCERs and the TECs of the involuted thymic tissue in case 3 are summarized in Table 2 . The staining profiles of the admixed lymphocytes within the CCERs and thymic tissue are given in Table 3 .

All CCERs and TECs showed crisp, circumferential membrane staining with AE1/AE3, CK5/6 Image 3A , CK7, CAM 5.2, and CK19. Both epithelial cell types had nuclei that were strongly p63+ Image 3B . Focal cytoplasmic positivity for vimentin was observed in the CCERs with strong positivity in TECs. CD99 was weakly positive in the cytoplasm of CCERs and TECs. Calponin displayed weak membrane staining in case 1 and in TECs. Both populations were negative for epithelial membrane antigen, smooth muscle actin, actin, and androgen receptor. General neuroendocrine markers (chromogranin and synaptophysin) were negative, as were stains for cells derived from local endocrine organs (thyroglobulin, thyroid transcription factor 1, parathyroid hormone, and calcitonin). CD10 and CD34 highlighted capillaries within the epithelial cell clusters, with the former showing variable mesh-like positivity around adjacent cells in thymic tissue and CCERs Image 3C .

View this table:
Table 1

As noted previously, there was a significant population of lymphocytes (as highlighted with CD45) within the typical thymic tissue in contrast with the CCERs. The former was composed predominantly of CD3–, CD1a–, and TdT+ thymocytes with fewer small CD20+ B cells. The rare lymphocytes in CCERs were composed of a mixture of B and T cells, and none were positive for CD1a or TdT.


Benign anatomic variants and developmental aberrations are not uncommonly encountered by surgical pathologists. While occasionally vexing, these findings are almost always incidental and bear minimal impact on diagnosis, prognosis, and therapy. It is important, however, to recognize these anomalies to prevent overinterpretation of their significance.

Image 1

A, Typical central cervical epithelial rest (CCER) morphologic features with nests and cords of epithelial cells intimately apposed to the adjacent adipose tissue (H&E, ×40). B, Typical bland cuboidal epithelial cells with rare lymphocytes (arrow) (H&E, ×400). C (Case 2), Rosette-like structures were observed (H&E, ×200). D (Case 3), A CCER showing a predominance of spindled epithelial cells (H&E, ×100).

Image 2

A central cervical epithelial rest (A) and involuted thymic tissue (B) that were present in the same paraffin block. The latter demonstrates a more prominent population of lymphocytes with well-developed Hassall corpuscles (A and B, H&E, ×200).

Owing to the complex sequence of events occurring during embryogenesis in the cervical region, a host of abnormalities or migration can lead to the presence of anomalous, epithelial-derived structures. Many well-described cysts, rests, heterotopias, ectopias, and even certain neoplasms likely arise from these aberrant epithelial elements that may cause diagnostic confusion.

The thymus traverses the neck en route to its mediastinal location, reaching the anterior mediastinum via the thymopharyngeal duct.3 During migration, small thymic fragments may dissociate from the developing organ and remain in postnatal life.1 At autopsy, cervical rests of thymic tissue are present in 20% of adults and more than 30% of children,3 often associated with the inferior parathyroid glands.1

Mirroring its embryologic complexity, the thymus undergoes marked alteration during life. Following childhood growth, the organ involutes with increasing fatty replacement through adult life. The majority of thymic remnants are present in the mediastinum and are usually composed of a prominent population of lymphocytes with occasional epithelial islands and Hassall corpuscles.1,2 More uncommonly (and perhaps later in the process), the involuted thymus is composed solely of spindled epithelial cells with partially cystic Hassall corpuscles.2,4

We describe a series of benign epithelial rests that were incidentally discovered in the central cervical region in patients undergoing surgery for papillary thyroid carcinoma and secondary hyperparathyroidism. Each CCER was distinct from the mediastinum, not apparent preoperatively, and not noticed grossly by the surgeon or pathologist.

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Table 3
Image 3

The epithelial cells in central cervical epithelial rests were positive for cytokeratin 5/6 (A) and p63 (B). CD10 highlights capillaries with encircled adjacent epithelial cells (C) (AC, ×200).

Microscopically, CCERs were morphologically similar and nearly identical to some mediastinal thymic remnants.2 They were composed entirely of clusters and cords of bland, nondescript epithelial cells intimately associated with the surrounding adipose tissue. Only rare, singly distributed lymphocytes were seen admixed with the epithelium. No CCER contained Hassall corpuscles. Immunostains revealed that the epithelial cells were positive for multiple cytokeratins (AE1/AE3, CK5/6, CK7, CAM 5.2, and CK19) and showed strong nuclear positivity for p63. Neuroendocrine and site-specific organ markers were negative. The rare lymphocytes that were identified within the CCERs were T and B cells, and none contained TdT+ or CD1a+ lymphocytes.

Several features suggest that CCERs represent remnants of thymic tissue deposited along the organ’s migration path. In case 2, the CCER was found in the region of an inferior parathyroid gland, previously described as a common location for thymic remnants. The epithelial cells shared many architectural and cytologic features of TECs, including the tendency for a clustering arrangement with focal, rosette-like formations and nearly identical nuclear features.2

By immunohistochemical analysis, CCERs and TECs had similar profiles. The keratin expression pattern of both is consistent with that previously reported in spindle cell TECs.5 It is interesting that CCERs and the involuted thymic parenchyma showed a CD10 and CD34 meshwork that extended from indwelling capillaries to surround immediately adjacent epithelial cells. Furthermore, CCERs and TECs showed strong nuclear p63 positivity. Dotto and colleagues6 recently showed that p63 expression was present in thymomas and all types of thymic epithelial cells in the normal thymus.

As noted, the majority of thymic remnants have a prominent population of lymphocytes. Each CCER was lymphocyte-poor. While abundant TdT+ and CD1a+ lymphocytes are usually seen in thymic tissue, no CCER had cells that were positive for these 2 markers (a phenomenon recognized in some mediastinal thymic remnants2).

The differential diagnosis includes other heterotopic epithelial elements, including misplaced cutaneous structures and salivary gland tissue.7 The deep location of CCERs argues against the former. The lack of well-developed myoepithelial elements (highlighted by virtually absent expression of muscle-related markers) makes a salivary origin less likely.

We have presented a series of epithelial rests that were incidentally encountered during the microscopic examination of tissue submitted from central neck surgery. They appeared as small collections of benign cuboidal to spindled epithelial cells with few associated lymphocytes, and immunohistochemical studies revealed that the epithelial cells had an immunophenotype similar to that of TECs. It is probable that CCERs represent a lymphocyte-depleted variant of thymic epithelial remnants that have not been well-described in the cervical region. Their primary importance lies in distinguishing these structures from a neoplastic process (especially papillary thyroid carcinoma). By being aware of these and other benign inclusions that may be encountered in the cervical region, incorrect diagnoses of malignancy may be avoided.


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