Опухоли легких, плевры, тимуса и сердца ВОЗ

areas containing inconspicuous thymic parenchyma containing numerous, often calcified, Hassall´s corpuscles {1352}. Myoid cells are present {907}. The thymic compartment may show single lymph follicles.

Differential diagnosis

Diagnosis of thymolipoma is usually not problematic. However, due to the large size of some lesions, careful sampling is necessary in order to rule out the possibility of atypical or malignant areas. In rare cases, thymomas may arise within thymolipomas {69}. Histologically, the main differential diagnoses include lipoma of the thymus (no thymic epithelial component) and mediastinal liposarcomas (scattered lipoblasts).

Histogenesis

The pathogenesis and biological nature of thymolipoma are controversial, but most

A

authors favour a benign neoplasm {69, 763,1352}. An origin from specialized thymic stroma has been postulated {69, 763}.

Prognosis and predictive factors

There have been no reports on recurrences, metastasis or tumour-related deaths, and local excision is curative.

Thymoma in thymolipoma

There is a single case report about thymoma within a thymolipoma occurring in a 67 years old female patient without myasthenia gravis {69}. The thymoma was classified as “cortical” (type B2). There was no recurrence within 10 years after radical surgery. We observed an almost identical case.

Lipoma

B

Lipoma is the most common benign mesenchymal tumour of the mediastinum {1529,1932}. In contrast to thymolipoma it does not contain foci of thymic parenchyma. Other rare benign lipomatous tumours are lipoblastoma/lipoblastomatosis {517}, hibernoma {31}, and angiolipoma {1031}.

Liposarcoma

Liposarcoma is the most common sarcoma in the anterior mediastinum, and some cases may represent thymic stromal sarcomas {801,938}, i.e. malignant counterparts of thymolipoma (thymoliposarcoma) {1030}. Mediastinal liposarcoma usually occurs in adults (mean age 43 years), and is rare in children {357}. In some cases, there is synchronous

involvement of other sites such as the retroperitoneum.

Well-differentiated liposarcoma is the most frequent subtype (60% of cases), including lipoma-like, inflammatory {1030} spindle cell {1138,1835}, leiomyomatous and dedifferentiated variants {601}, followed by myxoid liposarcoma (28%), and other subtypes (12%) {1030}, such as the highly aggressive pleomorphic liposarcoma {513}. In some cases, the presence of heavy lymphoid infiltration may result in mimicry of lymphoma or an inflammatory process {1030}.

Like the same tumour occurring in other sites, mediastinal myxoid liposarcoma shows TLS/FUS-CHOP fusion transcripts {1762}.

The tumours are curable by surgical excision in some patients {47,256, 357,740}, but recurrences develop in up to 32% of cases after a mean interval of 36 months. Myxoid liposarcoma has a worse prognosis than well-differentiated liposarcoma {1030}.

Solitary fibrous tumour

Definition

Solitary fibrous tumour (SFT) is an uncommon, locally aggressive mesenchymal neoplasm with highly variegating morphologic appearance, characterized by two basic elements encountered in varying proportions: a solid spindle cell component and a diffuse sclerosing component.

Epidemiology

Mediastinal SFT is a rare tumour of adults (28-78 years of age) {999}. Mediastinal SFT on average account for 15% of all SFT, and about 25% of extrapleural SFT {772,791,999,1384}.

Localization

Some mediastinal SFT may represent extensions from pleural SFT, but others arise from the mediastinal (including thymic) stroma {1685}.

Macroscopy

Mediastinal SFT can reach a large size, of up to 16 cm {2164}.

A

B

Fig. 3.116 Alveolar rhabdomyosarcoma. A Solid variant in the anterior mediastinum in a 2 monthsold girl. Primitive round cells are arranged in solid sheets, with focal alveolar pattern. Tumour cells have a high N:C ratio and dense chromatin, many apoptotic bodies and mitoses. B RT-PCR analysis of solid variant of alveolar rhabdomyosarcoma (RMS) in a 2 months old girl (same case as A). Note the 409 bp PAX3-FKHR fusion product in frozen tumour tissue (lower panel). Abbreviations: B, blank; NC, negative control (tonsil); PC, positive control [t(2;13) positive RMS]; S1, specimen 1, current case; S2-S3, two other RMS specimens negative for t(2;13); WT, wild type FKHR segment (324bp; upper panel). Molecular size markers (ladder) on the right side in the upper panel. For RT-PCR protocol see refs {114,658}.

has been observed in an example of mediastinal alveolar RMS of the solid variant {1742}. “Rhabdomyomatous thymomas” {1351,1730} with myoid cells, should not be mistaken for RMS.

Synovial sarcoma (SS)

Several cases of SS have been reported {871,2033,2163}. The tumours usually occur in adults but rarely in children {871} and manifest by pain, dyspnoea or superior vena cava syndrome. Most cases followed an aggressive clinical course, with 3 of 5 patients dying of tumour on followup of 10 months to 4 years. Detection of SYT-SSX chimeric RNA transcripts, resulting from the t(X;18) translocation is often essential to distinguish SS from mesothelioma, sarcomatoid (thymic and other) carcinomas, malignant peripheral nerve sheath tumour with glandular differentiation, germ cell tumour-associated sarcomas or metastases {71,2033}.

Vascular tumours

Mediastinal lymphangioma is a common mediastinal tumour in children {1932}. Hemangiomas of the cavernous, and less frequently, capillary subtype have been reported and may be complicated by the Kasabach-Merritt syndrome {838,1353, 1932}. Hemangiopericytoma, epithelioid hemangioendothelioma and angiosarcoma (the latter usually arising from a

Neurogenic tumours

Neurogenic tumours of the mediastinum occur almost exclusively in the middle and posterior compartments, where they constitute the most frequent neoplasms. However, benign schwannomas {1597}, and malignant peripheral nerve sheath tumours, including malignant Triton tumours {1525} have also been described in the anterior mediastinum, mainly in patients with neurofibromatosis {1726,1851}.

About 20% of mediastinal paragangliomas occur in the anterior compartment {1365} and they may be pigmented {1350}. They tend to occur in older individuals (mean age 46 years). The patients are asymptomatic, or present with compression symptoms, or rarely with Cushing syndrome {1548}. Posterior mediastinal paragangliomas tend to occur in younger patients (mean age 29 years), and about half of the cases have hypertension or other symptoms due to release of catecholamines by the tumours {1350}. They recur locally and metastasize in 55% and 26% of cases, respectively {1123}. Paragangliomas typ-

ically show a nesting pattern associated with a prominent vasculature. The tumour cells are immunoreactive for synaptophysin, and S100 protein positive sustentacular cells are often demonstrable around tumour cell nests. In contrast to neuroendocrine carcinomas, paragangliomas do not form ribbons or rosettelike structures, and cytokeratin is usually negative.

Tumours related to the sympathetic ganglia include neuroblastoma, ganglioneuroblastoma and ganglioneuroma. They occur almost exclusively in the posterior mediastinum, although neuroblastomas {70} and ganglioneuroblastomas have also been rarely described in the thymus {76,1964,2141}. In fact, neuroblastoma is the most common malignant tumour of the posterior mediastinum in young children. Ganglioneuroblastoma and ganglioneuroma occur mostly in adults.

Primary ependymoma of the posterior mediastinum in adults, is typically associated with a prolonged indolent course {503,2153}.

Other rare neoplasms

Other thymic/mediastinal soft tissue tumours include Ewing sarcoma which usually extends into the mediastinum from the thoracic wall {690}, malignant rhabdoid tumour {166,1160,1691}, inflammatory myofibroblastic tumour (inflammatory pseudotumour) {422,467}, calcifying fibrous tumour {1443}, giant cell angiofibroma {636}, elastofibrolipoma {455}, desmoid fibromatosis {1036}, benign mesenchymoma {2054}, rhabdomyoma {1315}, alveolar soft part sarcoma {593} and malignant fibrous histiocytoma {344,1932}.

Primary malignant melanoma {42,642, 1804,2088} probably arises from thymic nevus cell aggregates {642,1552}. Other rare tumours include meningioma {553, 2150}, osteosarcoma {454,739,888}, chondrosarcoma {1592}, giant cell tumour {622}, chordoma {32,1675,1910}, myelolipoma {1008,1706,1884}, and extramedullary haematopoietic tumours {449,834,1366,1400,1481,1788}.

J.K.C. Chan

Genetics of Tumours of Endocrine Organs”). Parathyroid adenomas are circumscribed or thinly encapsulated tumours comprising sheets, cords and acini of polygonal cells traversed by a delicate vasculature. There is often a mixture of tumour cells with clear, lightly eosinophilic and oxyphilic cytoplasm. Some tumours have abundant interspersed adipose cells (lipoadenomas) {1444,2167}. Mitotic figures are absent or rare, and focal nucleomegaly is acceptable. Parathyroid carcinomas often show capsular or vascular invasion, sclerotic bands, and mitotic figures. If there are uncertainties whether a neoplasm is of parathyroid origin, positive immunostaining for parathyroid hormone would provide a strong support for the diagnosis.

Histogenesis

Ectopic or supernumerary parathyroid gland in the anterosuperior mediastinum is the cell of origin for the ectopic parathyroid tumours. Such a localization for the parathyroid gland is not surprising since the inferior parathyroid glands share a common origin with the thymus from the third branchial pouch {2141}.

Fig. 3.124 Ectopic papillary thyroid carcinoma of the anterior mediastinum. The tumour comprises papillae lined by cells with overlapping and pale nuclei.

A B

Fig. 3.125 Ectopic parathyroid adenoma of the anterior mediastinum. A The tumour cells form packets and acini, separated by a delicate vasculature. Many clear cells are evident. B Positive immunostaining for parathyroid hormone provides confirmation that the tumour is of parathyroid origin.

Metastases to thymus and anterior mediastinum

H.K. Müller-Hermelink

Ph. Ströbel

A.Zettl

A.Marx

Malignant tumours that metastasize to the thymus or anterior mediastinum from distant primary tumours. Neoplasms that extend directly from adjacent organs or tissues are also included in this category.

The most common primary tumours involving these sites are lung, thyroid, breast and prostatic carcinomas {948, 1188,1287,1288,1305}, while melanoma and various sarcomas (liposarcoma, osteosarcoma, rhabdomyosarcoma, Kaposi sarcoma and malignant fibrous histiocytoma) are rare primary tumours {33,702,843,1852,1865}.

The distinction between squamous and neuroendocrine carcinomas of the thymus and mediastinal metastases with this differentiation can be difficult. In about 50% of carcinomas, morphological and immunohistochemical features can clarify the thymic derivation, while clinical staging procedures are required to clarify the derivation of the other cases. The different genetic characteristics of carcinomas of the thymus {896,2238,2242} compared to those of lung and the head and neck region {188,1582,1585,1866} are of diagnostic value.

Clinical data is also necessary to distinguish primary thymic melanomas {42, 642,1804,2088} or sarcomas {256,1742, 1932} from metastasis with a respective differentiation.

Table 3.14

A B

Fig. 3.126 Metastases to thymus and anterior mediastinum. A Summary of recurrent genetic gains and losses as determined by CGH discriminating between squamous cell carcinomas of the thymus, lung and head & neck region. There is considerable overlap between the carcinomas arising in the lung and head & neck. By contrast, the major genetic aberrations of thymic carcinomas are not shared with lung and head & neck carcinomas. B Diagnostic value of CGH-based genetic profiles for the distinction between squamous cell carcinomas of the thymus and mediastinal metastases of primary lung and head and neck tumours. Percentages indicate the probabilities for a primary lung or head and neck carcinoma in the presence of highly discriminating genetic alterations {188,1267,1866,2238}.

Fig. 3.127 Metastasis of an adenocarcinoma of the rectum to the thymus. Note the formation of thymic cyst adjacent to and infiltrated by the metastatic tumour.