Undescended retropharyngeal parathyroid adenoma with adjacent thymic tissue in a 13-year-old boy with primary hyperparathyroidism

ABSTRACT We describe a rare presentation of a symptomatic parathyroid adenoma located in an ectopic retropharyngeal position in a 13-year-old boy. Preoperative CT scan and MRI demonstrated the ectopic location of the parathyroid adenoma. The patient underwent successful parathyroidectomy with cure of his hyperparathyroidism. On pathologic exam, the specimen was made up of a parathyroid adenoma and adjacent thymic tissue, indicating that it was likely an undescended lower parathyroid gland arising from the third pharyngeal pouch. Ectopic retropharyngeal parathyroid adenomas are very rare and to our knowledge, none have been previously described in adolescents.

Tbx1 and Foxi3 genetically interact in the third pharyngeal pouch endoderm required for thymus and parathyroid development

SummaryThe mechanisms required for segmentation of the pharyngeal apparatus to individual arches are not precisely delineated in mammalian species. Here, using conditional mutagenesis, we found that two transcription factor genes, Tbx1, the gene for 22q11.2 deletion syndrome and Foxi3, genetically interact in the third pharyngeal pouch endoderm for thymus and parathyroid gland development. We found that Tbx1 is autonomously required for the endoderm to form a temporary multilayered epithelium while invaginating. E-cadherin for adherens junctions remains expressed and cells in the apical boundary express ZO-1. Foxi3 is required autonomously to modulate proliferation and promote later restoration of the endoderm to a monolayer once the epithelia meet after invagination. Completion of this process cooccurs with expression of Alcam needed to stabilize adherens junctions and extracellular, Fibronectin. These processes are required in the third pharyngeal pouch to form the thymus and parathyroid glands, disrupted in 22q11.2 deletion syndrome patients.

Concurrent intrathyroidal thymus and parathyroid in a patient with papillary thyroid carcinoma: a challenging diagnosis

Summary During embryogenesis, the thymus and inferior parathyroid glands develop from the third pharyngeal pouch and migrate to their definite position. During this process, several anatomic variations may arise, with the thyroid being one of the most common sites of ectopic implantation for both organs. Here, we report the case of a young female patient, who underwent total thyroidectomy for papillary carcinoma of the thyroid. The patient’s history was remarkable for disorders of the genitourinary system. Histologic examination revealed the presence of well-differentiated intrathyroidal thymic tissue, containing an inferior parathyroid gland. While each individual entity has been well documented, this is one of the few reports in which concurrent presentation is reported. Given the fact that both the thymus and the inferior parathyroid are derivatives of the same embryonic structure (i.e. the third pharyngeal pouch), it is speculated that the present condition resulted from a failure in separation and migration during organogenesis. Learning points: Intrathyroidal thymus and parathyroid are commonly found individually, but rarely concurrently. It is a benign and asymptomatic condition. Differential diagnosis during routine workup with imaging modalities can be challenging.

SOME ASPECTS OF EARLY DEVELOPMENT OF THE THYMUS: EMBRYOLOGICAL BASIS FOR ECTOPIC THYMUS AND THYMOPHARYNGEAL DUCT CYST. Algunas observaciones acerca del temprano desarrollo del timo: bases embriológicas del timo ectópico y del quiste del conducto timofar

Introducción. El objetivo principal de nuestro trabajo es el estudio histológico del desarrollo del timo humano entre la 5ª y la 8ª semana de gestación. Describimos varios términos embriológicos poco usados como: timo secundus, descensus thymi (la base embriológica para situar el timo en la garganta), ductus timicus (la base embriológica para el defecto innato llamado conducto timofaríngeo con posibilidad de formar un quiste). Material y método. Nuestras observaciones se basan en la investigación de 18 embriones humanos entre la 6ª y la 8ª semana de gestación. Resultados. La base del timo es común con la base de las glándulas paratiroideas. Es comparable con las bolsas faríngeas (saccus pharyngeus) en los embriones largos de 8 a 9 mm. La proliferación endodermal del epitelio en el tercer foco faríngeo (focus faringeus 3) es muy visible. La parte craneal y la parte dorsal son la base de origen de las glándulas paratiroideas inferiores. La parte caudal y la parte ventral son la base para el timo. Hemos observado también la notable proliferación del epitelio en la segunda bolsa faríngea, llamado por algunos autores Timo secundus. En nuestra opinión, en el ser humano no se forma un timo funcional en este lugar y la proliferación del epitelio en la mayoría de los casos, se detiene pronto. Conclusión. En este trabajo ofrecemos una vista general sobre la importancia clínica del desarrollo del timo y la descripción de los defectos innatos más frecuentes del mismo. Introduction. The aim of our morphological study is to describe the development of human thymus from 5th up to 8th week after fertilization in the context of its phylogenesis. We explicate some of the “forgotten” embryological terms with respect to their functions in thymic development, such as “thymus secundus”, “descensus thymi” (an embryological basis for cervical thymus) and “ductus thymicus” (an embryologic basis for a congenital anomaly called thymopharyngeal duct with possible thymic cyst). Material and methods. Our findings are based on the study of 18 human embryos from 6th to 8th week of development. Results. The first primordia of the thymus and parathyroid glands within the endoderm of pharyngeal pouches can be seen in 8 to 9 mm crown-to-rump-length stages. The most evident epithelial proliferation is visible in the paired third pharyngeal pouch (saccus pharyngeus tertius): the cranial dorsal part of pharyngeal pouch initiates the inferior parathyroid gland and the caudal ventral part of the pouch gives rise to the epithelial thymus. We found an obvious endodermal epithelial proliferation also in the second pharyngeal pouch. Some authors depict this proliferation as “thymus secundus”, but the proliferation of endoderm close down and the functional second thymus does not develop in human embryos. Conclusion. In our work we also review the clinical significance of early thymus development, as well as the most common developmental anomalies of thymus.

Parathyroid adenoma in third pharyngeal pouch cyst as a rare case of primary hyperparathyroidism

The primitive thymus and inferior parathyroid derive from the third branchial cleft. During embryonic development, these structures descend, reaching their final localisation. Third branchial cleft anomalies present usually as a fistula, abscess or cyst. However, there are no reports on parathyroid adenomas in the literature other than as a morphological possibility. We describe the case of a 47-year-old man, who had been diagnosed with arterial hypertension and who presented with a cervical mass at the edge of the lower third of the sternocleidomastoid muscle. On ultrasonography, the mass had a cystic walled appearance. Laboratory analysis only revealed an intact parathyroid hormone level of 140.5pg/ml. Sestamibi imaging showed a probable parathyroid adenoma in the anterior mediastinum. During surgery, a tract running from beyond the superior thyroid pedicle to the superior mediastinum was dissected and removed. In the inferior end of the tract, a brown mass was visible. Pathological examination revealed a thymus cyst surrounding a parathyroid adenoma. The primal alteration was the lack of division between the thymus and inferior parathyroid gland, and the prompt prevention of their development. In the case of our patient, a parathyroid adenoma had grown by chance.

Parathyroid anatomy, hormone synthesis, secretion, action, and receptors

Humans have two pairs of parathyroid glands lying in the anterior cervical region. The fetal parathyroid glands begin developing at 5 weeks from the third and fourth pharyngeal pouches. The third pharyngeal pouch, which contains tissue that will become the thymus and parathyroid, migrates downward and gives rise to the two inferior parathyroid glands normally located at the lower poles of the thyroid. The fourth pharyngeal pouch does not migrate and gives rise to the two upper parathyroid glands, which normally are attached to the upper poles of the thyroid (1).

Gene expression profile of the third pharyngeal pouch reveals role of mesenchymal MafB in embryonic thymus development

The thymus provides a microenvironment that induces the differentiation of T-progenitor cells into functional T cells and that establishes a diverse yet self-tolerant T-cell repertoire. However, the mechanisms that lead to the development of the thymus are incompletely understood. We report herein the results of screening for genes that are expressed in the third pharyngeal pouch, which contains thymic primordium. Polymerase chain reaction (PCR)–based cDNA subtraction screening for genes expressed in microdissected tissues of the third pharyngeal pouch rather than the second pharyngeal arch yielded one transcription factor, MafB, which was predominantly expressed in CD45−IA−PDGFRα+ mesenchymal cells and was detectable even in the third pharyngeal pouch of FoxN1-deficient nude mice. Interestingly, the number of CD45+ cells that initially accumulated in the embryonic thymus was significantly decreased in MafB-deficient mice. Alterations of gene expression in the embryonic thymi of MafB-deficient mice included the reduced expression of Wnt3 and BMP4 in mesenchymal cells and of CCL21 and CCL25 in epithelial cells. These results suggest that MafB expressed in third pharyngeal pouch mesenchymal cells critically regulates lymphocyte accumulation in the embryonic thymus.