Ectopic Hamartomatous Thymoma Research Articles

Branchioma: immunohistochemical and molecular genetic study of 23 cases highlighting frequent loss of retinoblastoma 1 immunoexpression.

Branchioma is an uncommon benign neoplasm with an adult male predominance, typically occurring in the lower neck region. Different names have been used for this entity in the past (ectopic hamartomatous thymoma, branchial anlage mixed tumor, thymic anlage tumor, biphenotypic branchioma), but currently, the term branchioma has been widely accepted. Branchioma is composed of endodermal and mesodermal lineage derivatives, in particular epithelial islands, spindle cells, and mature adipose tissue without preexistent thymic tissue or evidence of thymic differentiation. Twenty-three branchiomas were evaluated morphologically. Eighteen cases with sufficient tissue were assessed by immunohistochemistry, next-generation sequencing (NGS) using the Illumina Oncology TS500 panel, and fluorescence in situ hybridization (FISH) using an RB1 dual-color probe. All cases showed a biphasic morphology of epithelial and spindle cells with intermingled fatty tissue. Carcinoma arising in branchioma was detected in three cases. The neoplastic cells showed strong AE1/3 immunolabeling (100%), while the spindle cells expressed CD34, p63, and SMA (100%); AR was detected in 40-100% of nuclei (mean, 47%) in 14 cases. Rb1 showed nuclear loss in ≥ 95% of neoplastic cells in 16 cases (89%), while two cases revealed retained expression in 10-20% of tumor cell nuclei. NGS revealed a variable spectrum of likely pathogenic variants (n = 5) or variants of unknown clinical significance (n = 6). Loss of Rb1 was detected by FISH in two cases. Recent developments support branchioma as a true neoplasm, most likely derived from the rudimental embryological structures of endoderm and mesoderm. Frequent Rb1 loss by immunohistochemistry and heterozygous deletion by FISH is a real pitfall and potential confusion with other Rb1-deficient head and neck neoplasms (i.e., spindle cell lipoma), especially in small biopsy specimens.

Biphenotypic Branchioma: A Better Name Than Ectopic Hamartomatous Thymoma for a Neoplasm with HRAS Mutation.

Ectopic hamartomatous thymoma is a rare neck lesion originally thought to represent a non-neoplastic hamartoma, even though thymic origin has been questioned, and there is uncertainty about whether the lesion is a neoplasm. We investigated the genetics by performing targeted next generation sequencing (NGS). Three cases were identified from the authors' consultation files. A custom, targeted NGS panel including 1385 pan-cancer-related genes was performed on all cases. Three patients included 2 males and 1 female, aged 50, 58 and 70years, respectively (mean 59.3years), with tumors arising in the low anterior neck. All cases showed classical histologic features of EHT, with one case showing intraductal carcinoma in association with the EHT. By targeted NGS, one case harbored a hotspot HRAS mutation (p.Gln61Lys), while the other two cases only showed non oncogenic variants. Dual mesoderm and endoderm derivation/differentiation (biphenotypic) has been previously recognized, with epithelial and myoepithelial components, and arising from the apparatus contributing to neck development (branchial apparatus). Thus,EHT has been shown to havegenetic alterations inHRAS. These findings, without evidence of thymic derivation or an ectopic tissue location, strongly support that EHT is a true neoplasm. The name biphenotyic branchioma more correctly reflects the true nature of this dual mesoderm and endoderm derived tumor occurring in the lower neck.

Need for Re-Classifying the Rare Condition of Ectopic Hamartomatous Thymoma Based on Tumor Analysis

Ectopic hamartomatous thymoma is a rare neoplasm with classic anatomical location and characteristic histological and immunohistochemical features. Awareness of ectopic hamartomatous thymoma is essential to accurately diagnose these lesions which clinically mimics lipoma. Based on the morphologic and immunophenotypic features, the authors stress the need to discontinue the existing term of ectopic hamartomatous thymoma and replacing it with suitable nomenclature that aptly denotes its phenotype and possible histogenesis. The authors propose a new terminology “Triphasic Epithelial Myoepithelial Mesenchymal Branchial Anlage Tumor” as it encompasses three important constituents of the lesion (epithelial, myoepithelial, and mesenchymal) and its possible histogenesis in relation to branchial remnants.

Adenocarcinoma Arising in an Ectopic Hamartomatous Thymoma with HER2 Overexpression.

Adenocarcinoma Arising in an Ectopic Hamartomatous Thymoma with HER2 Overexpression.

A case of ectopic hamartomatous thymoma: controversy over the designation

BackgroundEctopic hamartomatous thymoma, which usually occurs in the lower neck, is a rare benign tumor containing spindle cells, epithelial nests, and adipose tissue. Although the origin of this tumor is still unknown, recent reports suggest that the designation of this tumor is inappropriate.Case presentationA 38-year-old with an anterior cervical mass in the suprasternal region of her neck was referred to our hospital. An ultrasound examination showed that the well-defined oval mass was 31 × 23 × 17 mm in size. A non-enhanced computed tomography scan of the neck revealed that the distinct neck mass in the subcutaneous tissue had a mixture of soft tissue and fatty components. The cervical tumor was clinically diagnosed to be an unusual lipoma with degeneration. The patient underwent the neck mass extirpation. During the surgery, the cervical mass was well demarcated and did not adhere to the surrounding tissues. The postoperative course was uneventful. The gross pathology report showed that the neck mass measured 3.0 × 2.5 × 2.0 cm. Microscopically, the tumor was composed of spindle cells, epithelial nests, and mature adipose tissue. Immunohistochemical examination revealed that both spindle cells and epithelial nests were positive for cytokeratin AE1/AE3. These histopathological findings were consistent with the features of ectopic hamartomatous thymoma. Over a follow-up period of 30 months, this patient exhibited no evidence of recurrence.ConclusionsEctopic hamartomatous thymoma should be considered in the differential diagnosis of subcutaneous tumors in the lower neck, when the CT shows the tumor has the mixed components of fat and soft tissues.

Ectopic Hamartomatous Thymoma-New Insights Into a Challenging Entity: A Clinicopathologic and Immunohistochemical Study of 9 Cases.

Nine cases of ectopic hamartomatous thymoma are described. The patients were 5 men and 4 women aged 34 to 52 years (mean, 43 y). All patients presented with solitary lower neck masses ranging in size from 3.5 to 8.0 cm (mean, 5.4 cm). Grossly, the lesions were circumscribed and lobulated masses with a fleshy white cut surface; cystic changes were identified in 3 cases. Histologically, the tumors were composed of varying proportions of spindle cells arranged in fascicles, mature adipose tissue, and an epithelial component composed of squamoid elements and glandular or ductal structures. In 1 case, duct-like structures dominated the histologic picture. Structures reminiscent of Hassall corpuscles were identified in 2 cases. No overt malignant changes were seen, and the mitotic activity ranged from 0 to 2 mitoses per 10 high-power fields. Immunohistochemically, the spindle cells coexpressed CK5/6, CD34, and smooth muscle actin, whereas the squamous component was positive for CK5/6 only. Bcl-2 was variably expressed in the spindle and epithelial elements, whereas Pax8 and STAT6 were uniformly negative. Clinical follow-up revealed that all patients were alive and well 2 to 5 years after diagnosis. Ectopic hamartomatous thymomas are benign neoplasms with a wide morphologic spectrum. The histologic and immunohistochemical features are reminiscent of thymic derivation and suggest possible origin from remnants of the thymic anlage. Changes in the nomenclature may be advised to more specifically designate tumor differentiation and to avoid confusion with true thymomas as these represent entirely separate clinicopathologic entities.

Spindle Epithelial Tumour with Thymus-like Differentiation (Settle): A Distinctive Malignant Thyroid Neoplasm: A Case Report

The spindle epithelial tumor with thymus-like element (SETTLE) is a very rare neoplasm related to the thyroid of young individuals. In 1991, Chan and Rosai unified the concept of SETTLE when they described 8 neoplasms situated in the neck and thyroid of children and young adults, previously diagnosed as malignant teratoma of the thyroid, thyroid spindle cell tumor with mucous cysts or thyroid thymoma. SETTLE is a distinct low-grade neoplasm, believed to be derived from branchial pouch or thymic remnants, with only 1 case report showing association with epithelium-lined cysts of possible branchial pouch derivation. It belongs to a group of cervical lesions that includes ectopic cervical thymoma, ectopic hamartomatous thymoma and carcinoma with thymus-like element (CASTLE). This tumor is composed predominantly of spindle and epithelioid cells with glandular or ductular structures lined by a mucinous or respiratory epithelium. In spite of indolent growth, SETTLE may give metastases many years after the diagnosis. Therefore, a long-term follow-up is required. We present one case, the first report from Sion Hospital, of a patient who has benign clinical course and tumoral features suggestive of a myoepithelial differentiation. The clinicopathologic features of the case reports in the literature are also reviewed. This case report showed the first report from our hospital and the possibility of a myofibroblastic differentiation. The SETTLE is among four tumors related to the thyroid, easily differentiated by clinicpathologic correlation. It is a lowgrade malignant neoplasm, with epithelial differentiation confirmed by immunohistochemical. Despite all the descriptions in the literature, this tumor remains with uncertain histogenesis and lacking convincing proof of thymic differentiation or branchial pouch derivation. SETTLE can metastasize a long time after the surgical resection. Because of this, the patients need long-term follow-up, with particular attention to monitoring the lungs.

The Reproducibility Index of Pathological Diagnosis and Rare Cases. The Results of the On-line Diagnostic Competition “Final Diagnosis”

Introduction/ Background UNIM Ltd. have created the SAAS platform DPathology that can be used for saving and studying histological slides and it doesn’t require an installation of a special software. You can use the platform with all the modern internet browsers. The SAAS platform gives all the specialists a chance to analyze remotely digital histological slides. It increases the accuracy of diagnostics and speeds up the medical assessment Aims To indicate the importance of collecting rare cases and expert assessment via digital microscopy Using the Digital Pathology© platform to carry out educational and competitive diagnostic measures. Methods Fourteen rare cases from different sub-specializations field in pathology were selected by UNIM LTD with expert’s pathologists from the Czech Republic and Italy and additionally validated in Norwayand theUK (blind method). The slides were digitized and introduced withclinical information to 250 specialists registered to take part in the competition “Final diagnosis”©. Results The range of the totally correct answers varies between 3 and 56 percent. The most difficult case for the participants was the one with no tumorous pathology: ectopic hamartomatous thymoma [1]. There were 3 percent of full match. The biggest number of full match to experts’ diagnoses can be seen in the case: Grade 2 central chondrosarcoma with 72% of agreement. To analyze the disagreements we divided them in two groups: Mayor disagreement – potentially not correct histological diagnosis will change the clinical tactics of patient’s treatment (considering the malignant pathology as a benign pathology, considering the benign pathology as a malignant, changing the stage of disease). Potentially wrong pathological diagnosis leads to wrong course of patient’s treatment and wrong chemotherapy, etc. Minor disagreement – potentially incorrect diagnosis doesn’t have any clinical matter. This tactic showed that the case of hyalinized endometrioid adenocarcinoma [ [2] turned out to be the most difficult one for the participants. The range of mayor disagreement here was 66 percent, mostly because cases was interpret as carcinosarcoma (63/93), while the agreement is 14 percent. And myxoinflammatory fibroblastic sarcoma of soft tissues [ 3], with major disagreement in 67.4% (pict case 10). All the data is shown in table 1. Agreement % Minor disagreement % Major disagreement % case1, N=97 Teratocarcinosarcoma of the nasal cavity [4] 0,12 0,61 0,26 case 2, N=89 Juxtaoral organ of Chievitz [5] 0,13 0,50 0,37 case3, N=93 Mammary Analogue Secretory Carcinoma of Salivary Glands, Containing the ETV6-NTRK3 Fusion Gene [6] 0,365 0,48 0,15 case 4, N=96 Low-grade sebaceous carcinoma of the skin [7] 0,10 0,68 0,23 case 5, N=99 t(6;11) translocation carcinoma (Ro- sette-forming tumor of the kidney) [8] 0,31 0,35 0,32 case 6, N=93 Hyalinized endometrioid adenocarcinoma [9] 0,14 0,20 0,67 case 7, N=96 Ectopic hamartomatous thymoma 0,03 0,82 0,15 case 8, N=91 Prolapse of the fallopian tube after hyster- ectomy 0,16 0,67 0,14 case 9, N=87 Phosphaturic mesenchymal tumor of soft tissues with calcification 0,23 0,34 0,33 case 10, N=92 Myxoinflammatory fibroblastic sarcoma of soft tissues [3] 0,13 0,20 0,67 case 11, N=87 Enchondroma 0,35 0,15 0,49 case12, N=88 Atypical chondromatous tumor/ Grade 1 chondrosarcoma 0,20 0,42 0,375 case 13, N=87 Grade 2 central chondrosarcoma 0,72 0,07 0,21

An ectopic hamartomatous thymoma compressing left jugular vein.

Ectopic hamartomatous thymoma (EHT) is an extremely rare benign neoplasm. It is usually found at the root of the neck (frequently on the left) and does not usually impact adjacent tissues in clinically significant ways. While EHT manifests distinct pathological features, the lesion is either asymptomatic or may show nonspecific clinical features. We report one case of EHT which was assumed to be of low malignant potential since it severely compressed the inlet of left internal jugular vein as seen by computed tomography scan. To the best of our knowledge, this clinical finding of EHT is very rare. After the diagnosis and treatment of this patient, we believe that EHT or suspected EHT should be treated less invasively.

A Case of Ectopic Hamartomatous Thymoma Occurring in the Neck

A Case of Ectopic Hamartomatous Thymoma Occurring in the Neck

Carcinoma showing thymus-like differentiation of the thyroid (CASTLE)

Carcinoma showing thymus-like differentiation (CASTLE) is a rare intrathyroidal neoplasm, probably arising from ectopic thymus or branchial pouch remnants. The tumor was first reported by Miyauchi et al. [1].The clinical and pathological features of this tumor were classified by Chan et al. [2] into 4 groups: ectopic hamartomatous thymoma, ectopic cervical thymoma, spindle ephithelial tumor with thymic-like differentiation (SETTLE), and carcinoma showing thymus-like differentiation (CASTLE). Recently, CASTLE has been designated as an independent clinicopathologic entity of thyroid tumors in the most recent edition of the World Health Organization classification of tumors of endocrine organs[3].To our knowledge, less than 100 cases of CASTLE have been reported in the literature, 45 cases of which (including one of the authors’ patient) have been identified in China. We report a new case of this entity and suggest recommendations for diagnosis.

Ectopic hamartomatous thymoma is distinct from lipomatous pleomorphic adenoma in lacking PLAG1 aberration

Ectopic hamartomatous thymoma is distinct from lipomatous pleomorphic adenoma in lacking <i><scp>PLAG</scp>1</i> aberration

A Case of Ectopic Hamartomatous Thymoma

Ectopic hamartomatous thymoma (EHT) is a rare and distinctive benign tumor that usually occurs in the supraclavicular, suprasternal areas. Histopathologically, it is characterized by a mixture of spindle cells, epithelial cells, and adipose cell elements. The recognition of EHT and differentiation of it from high-grade sarcomas such as synovial sarcoma is important, because EHT follows a benign clinical course and conservative surgical excision is the treatment of choice. We experienced a case of EHT in the supraclavicular area, so we present the case with a review of the related literatures.� Korean J Otorhinolaryngol-Head Neck Surg 2013;56:778-80 Key WordsZZEctopic hamartomatous thymoma ㆍSarcoma.

A Case of Ectopic Hamartomatous Thymoma Occurring in the Neck

Ectopic hamartomatous thymomas (EHT) is an extremely rare disorder. We report herein on a case of EHT occurring in the neck with a review of the literature. A 35 year-old man first noticed a swelling in his left cervical region at the beginning of March, 2005, and he came for a checkup in our department in March. In the initial examination, palpation revealed a 3×5 cm soft mass with a somewhat indistinct border in the left pars supraclavicularis plexus brachialis. There was no subjective symptom except swelling, and palpation revealed no anomaly in the cervical lymph nodes, and no other lesion was seen in the head and neck area. A tumor was present within the sternocleidomastoid muscle outside the left lobe of the thyroid gland, and the MRI imaging did not show any involvement of the thyroid gland. We performed a tumorectomy under general anesthesia. There was a tumor right under the sternocleidomastoid, there was no adhesions seen at the periphery of the tumor, and tumor removal went smoothly. The histological diagnosis was an ectopic hamartomatous thymoma. In 1984, Rosai et al. proposed the concept of the EHT as a lesion having the character of both a hamartoma and a tumor also comprising cervical ectopic thymic tissue. No recurrence has been reported in cases where the tumor has been totally extirpated. In our present case, no recurrence has been seen in a 7-year postoperative follow-up.

An ectopic hamartomatous thymoma

An ectopic hamartomatous thymoma is an extremely rare benign tumor of the lower neck that is the most common in middle-aged males. Pathologically, the tumor is characterized by a mixture of spindle cells, epithelial cells, mature adipose tissue, and lymphocytes. The histogenesis of this tumor is controversial. Recently, an origin from a remnant of the cervical sinus of His was proposed. Malignant lesions such as synovial sarcomas or malignant peripheral nerve sheath tumors can have similar clinical features and radiologic images. Thus, recognition of this tumor is important because it follows a benign clinical course and conservative surgical excision is the treatment of choice. Here, we report the case of a 34-year-old man with an ectopic hamartomatous thymoma in the left supraclavicular region and a review of the literature on this tumor.

Ectopic hamartomatous thymoma — A truly rare neoplasm: Report of a case

An ectopic hamartomatous thymoma is an extremely rare benign neoplasm that commonly occurs in the lower neck region. It has distinctive pathological features that include haphazardly arranged spindle cells, epithelial cells, and mature fat tissue. Its histogenesis is still controversial. This report presents a case of a 26-year-old man with ectopic hamartomatous thymoma in the left supraclavicular region, and discusses the current knowledge regarding this type of lesion. Clinicians as well as pathologists should be aware of the existence of this disease so that it can be identified correctly.

Ectopic hamartomatous thymoma: a case demonstrating skin adnexal differentiation with positivity for epithelial membrane antigen, androgen receptors, and BRST-2 by immunohistochemistry

Ectopic hamartomatous thymoma is a rare tumor of the lower neck occurring in adult men, which follows a benign course. They are triphasic with epithelial, adipocytic, and spindled elements in variable amounts. The origin of this tumor has been debated, but it is now believed to arise from remnants of the cervical sinus of His from early development. We describe a case of ectopic hamartomatous thymoma with typical features, as well as multifocal areas of skin adnexal differentiation. These included sebaceous, eccrine, and apocrine elements. We highlighted these by using immunohistochemistry to epithelial membrane antigen, BRST-2, and androgen receptors (AR). Epithelial membrane antigen stained sebaceous cells and the luminal borders of eccrine and apocrine ducts. BRST-2 and AR stained apocrine elements in a cytoplasmic and a nuclear pattern, respectively. The spindled component also expressed nuclear AR. AR positivity has not been described previously and may explain the occurrence primarily in men in postpubertal life.

Ectopic hamartomatous thymoma: a case report with immunohistochemical study and review of the literature

Ectopic hamartomatous thymoma (EHT) is a rare benign tumor. We present a case of EHT, which was seen as subcutaneous mass on the left supraclavicular area in a 19-year-old man. The tumor consisted of spindle cells, epithelial cells, adipose cells, and a small amount of lymphocytes, as described previously. Immunohistochemically, spindle cells were positive for keratin, a-smooth muscle actin, CD34 and vimentin, but negative for desmin and S-100 protein. Lymphocytes were positive for CD45RO but negative for CD20, CD1a, and CD99. Approximately, 5% of cells were positive for MIB-1 and no cells stained for p53 and bcl-2. Recognition of EHT is important and needs to be differentiated from high-grade sarcomas such as synovial sarcoma or glandular malignant peripheral nerve sheath tumor.

Ectopic hamartomatous thymoma growing in the sternocleidomastoid muscle masquerading as sarcoma

The distinction between ectopic hamartomatous thymoma and sarcoma is difficult, and preoperative biopsy and intraoperative histopathological examination fail to give a definitive diagnosis. It is important to recognise ectopic hamartomatous thymoma as one of the differential diagnoses of a cervical tumour.

Ectopic hamartomatous thymoma: a clinicopathologic and immunohistochemical analysis of 21 cases with data supporting reclassification as a branchial anlage mixed tumor.

This report describes the clinicopathologic and immunohistochemical findings in 21 cases of a highly distinctive tumor with a strong predilection for the lower neck region of adult males. Our study group consisted of 20 males and one female. The patients were 28 to 79 years old (mean age, 47 years; median age, 40 years), and they presented with solitary, lobular or multilobular masses ranging in size from 2.0 to 19.0 cm in greatest dimension (mean size, 5.1 cm; median, 4 cm). The tumors principally involved the lower neck region, usually in close proximity to the sternoclavicular joint. The preoperative duration of the lesions ranged from 2 months to 30 years. Histologically, the tumors were typically well marginated and composed of plump spindled cells, delicate spindled cells, mature adipose tissue, and epithelial cells, including both squamous and glandular elements. Epithelial-lined cysts were a focal finding in most cases and measured up to 2 cm in greatest dimension. Mitotic counts for the tumors ranged from 0 to 7 mitotic figures per 50 high power fields (mean mitotic count, 1.1 mitotic figures per 50 HPFs). Our immunohistochemical analysis revealed a complex immunophenotype with a diverse keratin profile. The plump spindled cells had a myoepithelial phenotype, as evidenced by the coexpression of keratins (5, 5/6, and 14), alpha-smooth muscle actin, CD10, and to a lesser extent, calponin. No compelling evidence for thymic differentiation was observed. The patients were initially managed by biopsy or partial resection (n = 4), simple local excision (n = 16), or an unspecified procedure (n = 1). Clinical follow-up of > or =3 years was available for 10 patients (48%). Two patients had recurrent disease, but there were no metastases or tumor-related deaths. A derivation from sequestered branchial epithelium is likely, but evidence for a thymic component is tenuous, at best. Our data support reclassification of this distinctive process as a branchial anlage mixed tumor. The differential diagnosis includes conventional mixed tumors of skin adnexal or salivary gland origin, synovial sarcoma, a peripheral nerve sheath tumor variant, and cystic teratoma.