Management of thyroid cytological material, preanalytical procedures and bio-banking.

Thyroid nodules are common and are increasingly detected due to recent advances in imaging techniques. However, clinically relevant thyroid cancer is rare and the mortality from aggressive thyroid cancer remains constant. Fine needle aspiration cytology (FNAC) is a standard method for diagnosing thyroid malignancy and the discrimination of malignant nodules from goitre. As the examined nodules on thyroid FNAC are often small incidental findings, it is important to maintain a low rate of undetermined diagnoses requiring further clinical work up or surgery. The most important factors determining the accuracy of the cytological diagnosis and suitability for biobanking of thyroid FNACs are the quality of the sample and availability of adequate tissue for auxiliary studies. This article discusses technical aspects (preanalytics) of performing thyroid FNAC, including image guidance and rapid on-site evaluation, sample collection methods (conventional slides, liquid-based methods, cell blocks) and storage (bio-banking). The spectrum of special studies (immunocytochemistry on direct slides or liquid-based cytology, immunohistochemistry on cell blocks and molecular methods) required for improving the precision of the cytological diagnosis of the thyroid nodules is also discussed.

Malignant peripheral nerve sheath tumour in the nasopharynx of a cow.

This case describes the findings in a Swiss Braunvieh cow with a malignant peripheral nerve sheath tumour (MPNST) in the nasopharynx. The major clinical signs were mixed dyspnoea with inspiratory and expiratory noises. Radiographic views of the head revealed an irregular mass with soft-tissue density in the nasopharynx originating from the dorsal pharynx and occupying and restricting the pharyngeal cavity. Endoscopic examination showed a lobulated mass obstructing almost the entire lumen of the aboral nasal passages and nasopharynx. Postmortem examination revealed a lobulated mass in the choanae with a broad attachment to the dorsal pharynx and histologically a soft tissue sarcoma with tumour cells positive for the S-100 and p75NTR (neurotrophin receptor) proteins and negative for CNPase. Electron microscopic examination showed few structures that indicated that the tumour originated from Schwann cells.

[Solitary fibrous tumour of the orbit: clinical, radiological, histological findings and differential diagnosis of an uncommon tumour]. / Solitärer fibröser Tumor der Orbita: klinische, radiologische, histologische Merkmale und Differenzialdiagnose eines ungewöhnlichen Tumors.

BACKGROUND: Solitary fibrous tumours (SFT) are mesenchymal neoplasias rarely found in the orbit. Due to their sharp delineation they are frequently mistaken for various benign neoplasma, such as cavernous hemangiomas, neurinomas and pleomorphic adenomas. We present two cases of SFT in the orbit and one in the lacrimal sac and discuss the radiological and histological differential diagnosis. PATIENTS AND METHODS: Among 9 patients diagnosed and operated in our department between 2008 and 2010 with an orbital tumour, three had the histological diagnosis of a solitary fibrous tumour. In 5 cases an MRI scan was performed preoperatively, in 4 cases a CT scan. RESULTS: Histology showed 2 pleomorphic adenomas, 2 cavernous hemangiomas, 2 neurinomas and 3 SFT. All SFT were intraoperatively well circumscribed and enucleated, showing histologically incomplete resection. No further treatment was given. There is no recurrence in any of the patients in the follow up of an average of 10 months (range 1 - 30 months). CONCLUSIONS: SFT are rare mesenchymal tumours of the orbit. The radiological differential diagnosis is difficult and they can be mistaken for more common tumours. The SFT has a wide range of histological appearances. Long term clinical follow-up is mandatory in all cases of SFT.

[Cytologic diagnosis of sarcoma]. / Zytologische Sarkomdiagnostik.

Soft tissue swelling represents a common clinical sign of a variety of neoplastic and non-neoplastic lesions. Sarcoma is rarely a cause. Fine needle biopsy as a minimally invasive, economic and accurate method is well suited for the diagnosis of inflammatory/infectious processes as well as of recurrent and metastatic disease. Cytologic diagnosis of primary soft tissue tumors is also feasible. It requires close collaboration with other medical disciplines and incorporation of clinical, radiological and morphologic findings. Clinical data such as age, gender, size and topography are important parameters. The differentiation of cells and properties of the extracellular matrix supplies clues for the differential diagnosis and forms the starting point for immunohistochemical or molecular analysis (FISH, RT-PCR). This analysis may be performed on cytological smears, paraffin embedded material of the cell blocks or on frozen material.

[Glomangiomatosis on the hand. A case report]. / Glomangiomatose der Hand. Ein Fallbericht.

Glomus tumours are solitary benign lesions most frequently located subungually on fingers and toes. In the rare case of a glomangiomatosis, the typical glomus cells are found on the altered vessel wall of the angiomatosis. Due to the rarity of this disease, no therapeutic golden standard has been mentioned in the literature, and a conservative treatment is usually adopted. The case of a 20-year-old craftsman with congenital, painful glomangiomatosis on his left dominant hand, progressively limiting the functionality of this limb, is reported. Two years after unsuccessful partial tumour resection, a surgical treatment based on radical tumour resection in terms of a finger amputation was performed. The 1-year follow-up showed no signs of pain for the patient.

Exploration of the APC/beta-catenin (WNT) pathway and a histologic classification system for pulmonary artery intimal sarcoma. A study of 18 cases.

APC, a tumor suppressor gene in the Wnt pathway, stabilizes beta-catenin and controls cell growth. Mutation of APC or beta-catenin leads to nuclear accumulation of beta-catenin and transcription of cyclin D1/cyclin A. Pulmonary artery sarcoma (PAS) were studied by morphologic, immunohistochemical, and molecular genetic methods of the Wnt pathway. Eighteen cases were included: mean age 52 years, primary intraluminal location with typical clinical presentation. PAS were classified as epithelioid (n = 4) or malignant fibrous histiocytoma (MFH; spindled/pleomorphic, n = 4), myxofibrosarcoma (n = 8), and one each hemangiopericytoma-like or malignant inflammatory myofibroblastic tumor-like. The tumor cells demonstrated vimentin, focal actins, and rare focal desmin positivity. All but one were grade 2 or 3 by FNCLCC grading. Alteration in chromosome 5q21 (APC) was found in 4/14 PAS by LOH, mostly epithelioid-type; an MFH-type case demonstrated microsatellite instability (MSI) and nuclear beta-catenin. Cyclin D1 was expressed in seven tumors, all myxofibrosarcoma-type. No mutations were detected in APC or beta-catenin. In summary, PAS are predominantly intermediate grade myxofibrosarcoma in middle-aged males, and fatal in two-thirds of patients. Despite myofibroblastic phenotype, APC/beta-catenin pathway changes are rare. Cyclin D1, only expressed in the myxofibrosarcoma-type, is likely transcribed via factors other than beta-catenin.

[Cytologic diagnosis of soft tissue tumors]. / Diagnose von Weichteiltumoren in der Zytologie.

Soft tissue swellings represent common clinical signs of a variety of neoplastic and non-neoplastic lesions. Sarcomas are rarely the cause. Fine needle biopsy as a minimally invasive, economic and accurate method is well suited for the diagnostics of recurrent and metastatic diseases. Cytologic diagnosis of primary soft tissue tumors is also feasible but requires close collaboration with other medical disciplines and incorporation of clinical, radiological and morphologic findings. Clinical data such as age, gender, size and topography are also important parameters. Differentiation of the cells and the properties of the extracellular matrix offer initial indications for the differential diagnosis and are the starting point for immunohistochemical and molecular analyses (FISH, RT-PCR). These analyses can be performed on cytological smears, on paraffin-embedded cell blocks on snap frozen material.

Relevance of translocation type in myxoid liposarcoma and identification of a novel EWSR1-DDIT3 fusion.

The clinical course of myxoid/round cell liposarcoma (MRCL) is characterized by frequent local recurrences and metastases at unusual sites. MRCLs carry specific translocations, t(12;16) or rarely t(12;22), linking the FUS or the EWSR1 gene with the DDIT3 gene, respectively. Nine FUS/DDIT3 and three EWSR1/DDIT3 variants of fusion transcripts have been described thus far. In search of prognostic markers for MRCL, we analyzed the translocation types of 31 patients and related them to the event free and overall survival. Using break-apart FISH and RT-PCR combined with DNA sequencing, we detected FUS/DDIT3 fusions in 30 sarcomas, while an EWSR1/DDIT3 translocation was identified in one tumor. FUS/DDIT3 type II (exons 5-2) was most commonly detected (20 cases), followed by type I (7-2) (7 cases) and type III (8-2) (3 cases). A single tumor carrying a t(12;22) translocation expressed a hitherto unknown EWSR1-DDIT3 fusion transcript (13-3) linking the complete RNA-binding domain of EWSR1 with a short piece of the 5'-UTR and the entire open reading frame of the DDIT3 gene. Interestingly, five of six patients with type I (7-2) FUS/DDIT3 fusions displayed local recurrences and/or metastatic spread within the first 3 years, generally requiring chemotherapeutical treatment (median disease-free survival 17 months). In contrast, 9 of 13 patients with type II FUS/DDIT3 translocations remained at 3 years disease-free (median disease-free survival 75 months). Since the total number of patients is still limited, further studies are required to verify a putative association of type I FUS/DDIT3-fusion transcripts with a prognosis of MRCL.

Late solitary bone metastasis of a primary pulmonary synovial sarcoma with SYT-SSX1 translocation type: case report with a long follow-up.

Primary synovial sarcoma outside its classical presentation in para-articular soft tissue of young patients is rare but regularly reported. One of the rarest primary locations is the lung. We describe a 73-year-old female patient who presented with a solitary malignant bone tumor 8 years after the resection of a lung neoplasm. The bone tumor was classified as an osteosarcoma and the lung tumor as an atypical carcinoid tumor at their first respective diagnostic work-ups. The resection of the affected humerus with allograft and endoprosthesis implantation followed. Reevaluation of the tumor samples at the time of the local recurrence of the bone tumor 6 years following the initial symptoms of the bone tumor lead to the reclassification of both specimens as synovial sarcomas. Both neoplasms contained the SYT-SSX1 type of the diagnostic translocation t(X;18) as detected by the reverse-transcription polymerase chain reaction analysis. The patient died 14 years after the resection of the primary synovial sarcoma of the lung and 6 years following the occurrence of the bone metastasis. This prolonged clinical course is uncommon for the SYT-SSX1 translocation, which, in other locations, is usually associated with an unfavorable prognosis.

Gorham-Stout disease of the shoulder girdle and cervico-thoracic spine: fatal course in a 65-year-old woman.

A case of Gorham-Stout disease of the shoulder girdle and cervico-thoracic spine in a 65-year-old woman is described. The patient presented with progressive neurologic symptoms, pain, and deformities of the cervico-thoracic spine as well as of her left shoulder following a traumatic shoulder luxation. Since the patient had a history of uterine carcinoma, the current disease was clinically difficult to differentiate from osteolytic metastases. The results of the clinical, radiological and histopathologic examination leading to the diagnosis of Gorham-Stout disease are described. Neither attempted surgery nor radiotherapy produced clinical improvement and the patient died 1 year after the first clinical evaluation.

Gains of 12q13-14 and overexpression of mdm2 are frequent findings in intimal sarcomas of the pulmonary artery.

The characterization of clinical, histopathological, immunohistochemical, and genetic features of intimal sarcomas arising in the pulmonary artery is presented in this study. Four resected lungs, one endarterectomy specimen and three biopsies from eight patients (four males and four females; median age 41 years) suffering from intimal sarcomas of the pulmonary artery using conventional stains, immunohistochemistry, and comparative genomic hybridization (CGH) were analyzed. The predominant clinical presentation was dyspnea (all eight patients) and febrile pulmonary disease (six of eight). Signs of embolic lung disease were present in all patients. One patient died postoperatively, six patients died of disease 8-35 months after presentation, and one patient was alive 6 months after surgery. Histopathological examination of the submitted material showed spindle cell, partially myxoid and pleomorphic sarcomas. Metastases were histologically confirmed in three patients (lung, pleura, and skull). Immunohistochemically, vimentin was strongly expressed in all tumors. Focal positivity was observed for alpha smooth muscle actin, CD117, CD68, p53, and bcl2. No reaction could be obtained for endothelial markers. The proliferation index Ki-67 was between 5% and 80%. Six examined tumors were positive for mdm2. In the CGH analysis, gains and amplifications in the 12q13-14 region were found in six of eight tumors (75%). Other, less consistent alterations, were losses on 3p, 3q, 4q, 9p, 11q, 13q, Xp, and Xq, gains on 7p, 17p, and 17q, and amplifications on 4q, 5p, 6p, and 11q. Intimal sarcomas of the pulmonary artery are tumors with an unfavorable prognosis and poorly differentiated morphology. A majority of tumors show a consistent genetic alteration (gains and amplifications in the 12q13-14 region) and overexpression of mdm2, implicating the mdm2/p53 pathway as a possible mechanism in the tumor pathogenesis.

Distribution of the large aggregating proteoglycan versican in adult human tissues.

We studied the distribution of the large hyaluronan-binding proteoglycan versican (also known as PG-M) in human adult tissues using affinity-purified polyclonal antibodies that recognize the core protein of the prominent versican splice variants VO and V1. Versican was present in the loose connective tissues of various organs and was often associated with the elastic fiber network. Furthermore, it was localized in most smooth muscle tissues and in fibrous and elastic cartilage. Versican staining was also noted in the central and peripheral nervous system, in the basal layer of the epidermis, and on the luminal surface of some glandular epithelia. In blood vessels, versican was present in all three wall layers of veins and elastic arteries. In muscular arteries the immunoreactivity was normally restricted to the tunica adventitia. However, it appeared in the media and the split elastica interna of atherosclerotically transformed vessel walls. Our survey of the distribution of versican in normal human tissues now forms the basis for extended studies of potentially aberrant versican expression during pathogenic processes.

[Colon carcinoma simulating retroperitoneal inflammatory pseudotumor. Case report of so-called abdominal inflammatory fibrosarcoma]. / Kolonkarzinom-simulierender retroperitonealer inflammatorischer Pseudotumor. Kasuistik eines sogenannten abdominellen inflammatorischen Fibrosarkoms.

Resection of a stenosing colon tumor in an 89-year-old male patient led to the diagnosis, unusual at this age, of an inflammatory pseudotumor (synonym: plasma cell granuloma) of the retroperitoneum and mesentery, which invaded the large bowel and showed infiltration of one regional lymph node. Histology and immunohistochemistry (demonstrating a myofibroblastic phenotype of the proliferating spindle cells and polyclonality of abundantly present plasma cells) of the specimen resembled previously reported lesions in various locations. The etiology and exact nosological classification of inflammatory pseudotumors are not yet unequivocally settled. The recently published conjecture that such lesions of the retroperitoneum represent a separate entity with features of a malignant neoplasm is discussed.

[Leiomyosarcoma in the thyroid gland--primary tumor or metastasis?]. / Leiomyosarkom in der Schilddrüse--Primärtumor oder Metastase?

In a 69-year-old female patient a moderately pleomorphic spindle-cell thyroid tumour measuring 5 cm in diameter was initially misinterpreted as primary anaplastic thyroid carcinoma. During clinical investigations to elucidate the cause of severe anaemia, 17 months later an ulcerated duodenal leiomyosarcoma was detected and removed by duodenopancreatectomy. Reevaluation of the thyroid nodule led to revision of the initial diagnosis to metastatic leiomyosarcoma. Six months later the patient died from cerebral stroke. Autopsy findings confirmed the diagnosis of primary leiomyosarcoma of the duodenum with initial manifestation as thyroid metastasis.