Agressive fibromatosis: genetic and biological correlations

Aggressive fibromatosis, also known as desmoid tumor, is specific and relatively rarely occuring disease. It belongs to heterogenous group of soft tissue tumors. Originally, it arises from fibroblasts with monoclonal proliferation derived from fibro-aponeurotic tissue with typical local invasive spreading without metastatic tendency. Increased amount of knowledge about the role of the APC gene and its protein product in FAP play an important role in revealing the molecular nature of desmoid tumors. In general, we can conclude that the β-catenin dysregulation is the key player of the FAP associated desmoid tumor onset. The Wingless/Wnt cascade plays a crucial role in the pathogenesis of aggressive fibromatosis. However, it has not been definitely proven that the mutations of APC or β-catenin genes are the trigger mechanisms. The research outcome can pave the way for using target biological therapy in routine practice in patients with aggressive fibromatosis in the future.     

<Emphasis Type="Italic">APC</Emphasis> mosaicism in a young woman with desmoid type fibromatosis and familial adenomatous polyposis

Familial adenomatous polyposis (FAP) is usually caused by germline mutations in the adenomatous polyposis coli (APC) gene. The classic form is characterized by hundreds to thousands of adenomas in the colorectum and early onset colorectal cancer (CRC) if left untreated. FAP is also associated with multiple extra-colonic manifestations such as gastroduodenal polyps, osteomas, epidermoid cysts, fibromas and desmoids. Most desmoid tumours in FAP patients occur intra-abdominally. Approximately 15–20% of the APC mutations are de novo mutations. Somatic mosaicism has been reported in some sporadic cases of polyposis but is probably an underestimated cause of the disease. This case report presents the detection of a mosaic APC mutation in a 26-year-old woman who as a child had been diagnosed with desmoid type fibromatosis. FAP was suggested when she presented with extensive extra abdominal fibromatosis. Our findings indicate that APC mutations may be suspected in patients presenting with a desmoid regardless of its location. If there is clinical evidence that the patient has FAP, adenomas and colonic mucosa in addition to leukocyte DNA should be included in the screening, preferably using methods that are more sensitive than Sanger sequencing.     

Incidental cystic endocrine tumor of the pancreas: A case report with immunohistochemical study

A large cystic lesion in the pancreatic tail was found incidentally in a 20-year-old female during laparoscopic cholecystectomy. Pre-operative work up had revealed calculi in gall bladder and in addition, a cystic lesion in pancreas suggesting the possibility of a pseudocyst. A laparoscopic enucleation of the cyst was performed along with the removal of gallbladder. Microscopic examination of the resected specimen revealed a pancreatic cystic endocrine tumor; however, this tumor had produced no symptoms. Immunohistochemical studies of the tumor cells showed positivity for neuron-specific enolase, chromogranin A, and synaptophysin indicating their neuroendocrine nature. Prognostic markers (CK19, CD10 and Ki67) indicated good prognosis. Although endocrine tumors of the pancreas are usually solid, cystic change occurs only rarely and such tumors should be considered in the differential diagnosis of patients who have a cystic lesion in the pancreas in view of their rare transformation into a malignant tumor.     

Fibromatose agressive de la paroi abdominale (tumeurs desmoïdes)

The aggressive fibromatosis or desmoid tumours are rare fibrous infiltrating proliferations. They developed from the fascia and muscle. They are benign with local aggressiveness but never express metastasis. The treatment requires a multidisciplinary study with integrating surgeon, chemotherapy and radiation oncologist. Prognosis is generally good. Between 1997 and 2008, four desmoid tumors were treated in surgical B department. Clinical and radiological signs had reported the diagnosis in all the cases. A tumor resection with a safety margin has been performed in all patients. Histological exam confirmed the diagnosis. The aggressive fibromatosis are rare tumours with a distinctive genetic and pathogenic profile. Although, they are benign, they have a true local malignancy and a constant tendency to recidivism. A better comprehension of their physiopathology with a multidisciplinary assumption is fundamental for an adequate therapeutic approach.     

Solitary true cyst of the pancreas in an adult

Background: Solitary true cyst of the pancreas is rare in adults, and the differential diagnosis of cystic lesions of the pancreas is challenging. Aim of the Study: To describe a solitary true cyst of the pancreas in an adult and discuss the differential diagnosis. Methods: A 50 yr old woman presented with a mass lesion in the right upper quadrant of the abdomen. Abdominal computed tomography showed a cystic lesion, with a maximum diameter of 12 cm, between the inferior surface of the liver and the ascending colon. The cyst was homogenous and had smooth edges. On magnetic resonance imaging, a unilocular cyst was seen that was low intensity on T1-weighted images and very high intensity on T2-weighted images. No connection between the cyst and the pancreatic ductal system was demonstrated on endoscopic retrograde cholangiopancreatography. Laparotmy was performed with a presumptive diagnosis of cystic tumor of the pancreas. Results: On pathologic examination, the cyst was serous and was lined with a single layer of normal cuboidal epithelium that was periodic acid Schiff stain negative. Meticulous examination failed to identify honeycomb-like microcysts characteristic of serous cystadenoma. The final diagnosis was a solitary true cyst of the pancreas. Conclusion: The differential diagnosis of solitary true cyst from other cystic lesion of the pancreas usually is based on histology. Particular care must be taken to distinguish this lesion from macrocystic serous cystadenoma.     

Values of carcinoembryonic antigen, elastase 1, and carbohydrate antigen determinant in aspirated pancreatic cystic fluid in the diagnosis of cysts of the pancreas

The levels of carcinoembryonic antigen (CEA), elastase 1, and carbohydrate antigen determinant (CA 19-9) in the pancreatic cystic fluid and the serum from five patients with cystadenocarcinoma of the pancreas, one patient with retention cyst due to pancreatic carcinoma, three patients with cystadenoma, and eight patients with benign pseudocyst accompanying or following pancreatitis, were determined by immunoassay technique. Fluid from pancreatic cysts was obtained by ultrasonically-guided percutaneous fine-needle aspiration biopsy. The specimens were centrifuged and the supernatant was used for the measurement of CEA, elastase 1, and CA 19-9, while the cell pellet was examined cytologically. The levels of CEA in the aspirated fluid were significantly higher in patients with malignant cysts of the pancreas than in those with benign cystadenomas and pseudocysts. In contrast, the levels of elastase 1 were significantly lower in patients with malignant cysts than in those with benign pancreatic cysts. Although the levels of CA 19-9 were significantly higher in patients with malignant cysts than in those with pseudocysts, the overlap between the values of patients with malignant and benign pancreatic cysts is too great. The serum CA 19-9 was most useful, however, to distinguish an individual patient with malignant cysts of the pancreas from those with benign pancreatic cyst, since there were no significant differences between the levels of serum CEA and elastase 1 in patients with malignant and benign pancreatic cysts. Correct diagnoses were made cytologically in 4 (66.7%) of 6 patients with malignant cysts. In two patients with malignant cyst, in whom no cancer cells were detectable in the aspirated materials, levels of CEA were abnormally high, but high levels of elastase 1 did not occur. Therefore, the combined measurement of CEA and elastase 1 in the aspirated cystic fluid of the pancreas could be used as an aid in diagnosis of malignant cysts of the pancreas.     

Phenotypic variation in hereditary nonpolyposis colon cancer syndrome. Association with infiltrative fibromatosis (desmoid tumor).

Familial infiltrative fibromatosis (desmoid tumor) is a recognized complication of familial adenomatous polyposis (FAP) but has not been described in families without colonic polyposis. The authors describe a unique family in which a predisposition to infiltrative fibromatosis and nonpolyposis colon cancer was inherited dominantly through four generations. This report expands the range of phenotypic variation described for the hereditary nonpolyposis colon cancer (HNPCC) syndrome and adds to the extracolonic complications that are common with FAP and HNPCC.     

Dacarbazine-Doxorubicin therapy ameliorated an extremely aggressive mesenteric desmoid tumor associated with familial adenomatous polyposis: report of a case

A 30-year-old man with familial adenomatous polyposis (FAP)underwent prophylactic proctocolectomy by laparoscopy-assistedsurgery. After 10 months, we found an intra-abdominal tumor,which grew rapidly to 25 cm in diameter. We performed an emergencyoperation, which revealed that it was a desmoid tumor derivedmainly from colorectal mesenterium. The tumor was removed withthree short segments of intestine and the left ureter. A computedtomography (CT) scan done 3 months later showed a 10 cm mesentericdesmoid tumor at the beginning of jejunum, approaching the rootof the superior mesenteric artery (SMA). Fortunately, we wereable to remove the tumor without injuring the SMA. To our distress,however, another recurrent mesenteric desmoid tumor was discoveredin the pelvis one month later, which grew rapidly from 5 cmto 16 cm within 4 months. During this period, we gave the patientseveral regimens, including antiestrogen (tamoxifen), a nonsteroidalanti-inflammtory drug and imatinib mesylate (Gleevec), whichhad little or no effect. Finally, when the desmoid occupiedthe pelvic space, we gave the patient dacarbazine (DTIC) anddoxorubicin (DOX). After seven courses, the mesenteric tumorshowed an almost complete response (CR). The chemotherapy causedgrade 3 to 4 leukocytopenia, but without any hazardous events.No evidence of further recurrence of mesenteric desmoid hasbeen seen for 4 years. This combination chemotherapy is a promisingstrategy, even against an extremely aggressive, life-threateningmesenteric desmoid associated with FAP.     

Treatment of desmoids and mesenteric fibromatosis in familial adenomatous polyposis with raloxifene

BACKGROUND: Among the great variety of extracolonic manifestations of familial adenomatous polyposis, the most serious are desmoids and fibromatosis of the abdominal cavity. These may be a danger to the patient and a concern to the clinician. Pharmacological management of this relentless problem is favored by surgical intervention. At present, however, beneficial actions of medical therapy are not separable from undesirable side effects. METHODS: We studied the effects of 120 mg daily of raloxifene, a non-steroidal benzothiophene, on progressive desmoid tumors and mesenteric fibromatosis by evaluation of lesion size and symptoms in 13 patients with familial adenomatous polyposis, selected on the basis of intra-abdominal localization of the lesion, on refractoriness to other medical treatments, and on estrogen receptor-alpha expression. RESULTS: The patients had a significant response to raloxifene therapy, with complete remission in 8 cases and partial response in 5 cases, evaluated by regression of symptoms and tumor size. Serum biochemical parameters did not show any significant changes. Side effects were never observed. CONCLUSIONS: Although the number of patients included in the study is limited and in spite of some limitations, the available results support that, in the evaluation of response, daily therapy with raloxifene decreases desmoid tumor and mesenteric fibromatosis size and symptoms and does not cause side effects. These findings offer a novel option in the pharmacological treatment of desmoids, leading to medical therapy of these neoplastic lesions in familial adenomatous polyposis patients.     

Desmoid-type fibromatosis-associated Gardner fibromas: prevalence and impact on local recurrence

Although Gardner fibroma is a precursor lesion of desmoid tumor, the prevalence and prognostic importance of Gardner fibroma associated with desmoid tumors has not been systematically studied in adults. From 129 patients with desmoid-type fibromatosis, 170 specimens were re-examined for the presence of an associated Gardner fibroma. Clinicopathologic features of Gardner fibroma-associated desmoid-type fibromatosis were compared to desmoid tumors without associated Gardner fibroma. Recurrence-free survival was compared using multivariate Cox proportional hazard regression to account for known confounding factors. Of 104 evaluable primary desmoid tumor resections, 25 (24%) had an associated Gardner fibroma. When previous incisional biopsies and resection specimens of locally recurrent desmoid tumors were also examined, the overall prevalence of associated Gardner fibroma was 37%. Desmoid tumors arising in high risk anatomic sites (extremities or deep soft tissues of the back and chest wall) were more often associated with Gardner fibroma than tumors at other sites. Median recurrence-free survival for patients with Gardner fibroma-associated desmoid-type fibromatosis was 3.2 years, whereas median survival for patients without associated Gardner fibroma was >25 years (hazard ratio 2.8; P = 0.001). Although the presence of Gardner fibroma had no impact on the recurrence rate of desmoid tumors arising at high risk anatomic sites, associated Gardner fibroma increased the risk of recurrence 4-fold for desmoid tumors at low risk anatomic sites. Associated Gardner fibroma is under-recognized in desmoid-type fibromatosis and increases the risk of local recurrence for a subgroup of patients.     

Clinical significance of magnetic resonance cholangiopancreatography for the diagnosis of cystic tumor of the pancreas compared with endoscopic retrograde cholangiopancreatography and computed tomography.

BACKGROUND: Cystic tumor of the pancreas has been investigated by a variety of imaging techniques. Magnetic resonance cholangiopancreatography (MRCP) is being widely used as a non-invasive diagnostic modality for investigation of the biliary tree and pancreatic duct system. The purpose of this study was to compare MRCP images with those of endoscopic retrograde cholangiopancreatography (ERCP) and computed tomography (CT) in order to clarify the diagnostic efficacy of MRCP for cystic tumor of the pancreas. METHODS: We retrospectively studied 15 patients with cystic tumor of the pancreas that had been surgically resected and histopathologically confirmed. There were five cases of intraductal papillary adenocarcinoma, five of intraductal papillary adenoma, two of serous cyst adenoma, two of retention cyst associated with invasive ductal adenocarcinoma and one of solid cystic tumor. RESULTS: In all cases MRCP correctly identified the main pancreatic duct (MPD) and showed the entire cystic tumor and the communication between the tumor and the MPD. On the other hand, the detection rate by ERCP of the cystic tumor and the communication between the cystic tumor and the MPD was only 60%. Although the detection rates by CT for the septum and solid components inside the cystic tumor were 100 and 90.0%, respectively, those of MRCP for each were 58.3 and 20.0%. CONCLUSION: MRCP is capable of providing diagnostic information superior to ERCP for the diagnosis of cystic tumor of the pancreas. Although MRCP may provide complementary information about the whole lesion of interest, the characteristic internal features of cystic tumor of the pancrease should be carefully diagnosed in combination with CT.     

Familial adenomatous polyposis: not all masses are desmoids

Familial adenomatous polyposis (FAP) is a multi-system disease characterised by the development of hundreds to thousands of colorectal adenomas which inevitably progress to carcinoma without treatment. It is commonly associated with extra colonic lesions including osteomas, epidermoid cysts and desmoid tumours. Desmoid tumours are troublesome due to their size and bulk and are a significant cause of morbidity and mortality in FAP. This series highlights three cases in which patients with FAP developed masses thought initially to be manifestations of the condition. Further investigation in fact demonstrated neurofibromatosis type 1 in all three patients. All masses in FAP patients cannot be assumed to be disease related (desmoid, osteoma, epidermoid cyst or carcinoma).     

An unusual case of extra‐abdominal desmoid tumour

ZAMPIERI N., CECCHETTO M., ZORZI M.G., PIETROBELLI A., OTTOLENGHI A. & CAMOGLIO F. (2010) European Journal of Cancer Care 19 , 410–412
An unusual case of extra‐abdominal desmoid tumour Desmoid tumour is relatively rare and generally non‐metastatisizing lesion of mesenchymal origin composed of fibrous tissue and fitting in the group of aggressive fibromatosis; it is a locally aggressive proliferative soft‐tissue lesion with controversial nature. This tumour accounts for 0.03% of all tumours and 3% of soft‐tissue tumours with annual incidence of two to four cases per million. Although desmoid tumours are more common in persons aged 10–40 years than in others, they do occur in young children and older adults; in children the sex incidence is equal. This is a rare case of extra‐abdominal desmoid tumour in a 14‐year‐old girl affected by spastic tetraparesis. To our knowledge no similar cases are present in literature to date.     

A Case of Pancreatic Intraepithelial Neoplasia That Was Difficult to Diagnose Preoperatively

A 63-year-old female patient presented to a local physician with pain in her back and epigastric region. An abdominal computed tomography (CT) scan revealed a pancreatic tumor, and the patient was referred to our hospital. Multiple imaging studies that included ultrasonography (US), CT, MRI, and endoscopic US revealed a cystic lesion 3–4 cm in size with node-like projections in the body of the pancreas. The distal main pancreatic duct was also found to be dilated. Endoscopic retrograde pancreatography revealed an irregular stenosis of the main pancreatic duct proximal to the cystic lesion, and malignancy was suspected. The patient was preoperatively diagnosed with pancreatic ductal carcinoma concomitant with intraductal papillary mucinous carcinoma, and a distal pancreatectomy was performed. Rapid pathological diagnosis during surgery revealed positive surgical margins for pancreatic intraepithelial neoplasia (PanIN). Further resection was performed twice, her surgical margin was positive and total pancreatectomy was ultimately conducted. Histopathological findings revealed diffuse microinvasive cancerous lesions corresponding to PanIN-2 (moderate dysplasia) to PanIN-3 (carcinoma in situ) throughout the pancreas. PanIN involves microlesions of the ductal epithelium that may precede pancreatic cancer. Ascertaining changes in PanIN using images provided by diagnostic modalities such as CT and US is challenging. Ductal stenosis and distal cystic lesions resulting from atrophy and fibrosis of pancreatic tissue were noted around PanIN. Considering the possibility of PanIN, a precancerous lesion during differential diagnosis will help to improve early detection and prognosis for patients with pancreatic cancer.Key Words: Pancreatic intraepithelial neoplasia, Pancreas cancer, Pancreatic duct stenosis, Pancreatic cyst, Diagnosis     

Fibromatosis of Thyroid Gland-A Case Report

Fibromatosis covers a broad group of benign fibrous tissue proliferations of varied microscopic appearances that are intermediate in their biological behaviour between bengin fibrous tumour and fibrosarcoma, Extra abdominal fibromatosis in the neck occassionally cause serious sequellae when aggressive invasion of vital structure occurs. However, the principle of wide excision is difficult to apply in some patients because of the important organs surrounding the tumour. We describe a primary spindle cell tumour of thyroid that raised initial diagnostic problems and was eventually diagnosed as fibromatosis of thyroid gland.     

Cystic neoplasms of the pancreas: a heterogeneous disorder.

Cystic neoplasms of the pancreas are rare tumors with a relatively better prognosis as compared to other pancreatic cancers. They may be mistaken for pseudocysts. Seventeen patients who underwent surgical resection were analyzed. Seventy percent of the patients were females and 76.7% of the tumors were located in the tail of the pancreas. Preoperative diagnosis was made on the basis of ultrasonography and/or computed tomography findings in 60% of patients. Retrospective review of the imaging modalities revealed one or more findings suggestive of cystic neoplasms in 90% of the patients. These included multiloculated cysts, thickened cyst wall, intracystic mass or calcifications, and presence of liver metastasis. All the tumors were completely or partly excised. The final histopathological diagnosis was microcystic adenoma in 2, mucinous cyst adenoma in 1, papillary cystic neoplasm in 3, cystic neuroendocrine tumor in 5, and cystadenocarcinoma in 6. Of the 17 patients, 10 had malignant tumors. Seven patients with benign tumors and 3 patients with malignant tumors are disease free 12-30 months after resection. Cystic neoplasm must always be considered as a possibility when dealing with cystic lesions of the pancreas and a careful evaluation of ultrasonography and computed tomographic scan may give a clue to the diagnosis.     

Gene Expression Profiling in Familial Adenomatous Polyposis Adenomas and Desmoid Disease

Gene expression profiling is a powerful method by which alterations in gene expression can be interrogated in a single experiment. The disease familial adenomatous polyposis (FAP) is associated with germline mutations in the APC gene, which result in aberrant β-catenin control. The molecular mechanisms underlying colorectal cancer development in FAP are being characterised but limited information is available about other symptoms that occur in this disorder. Although extremely rare in the general population, desmoid tumours in approximately 10% of FAP patients. The aim of this study was to determine the similarities and differences in gene expression profiles in adenomas and compare them to those observed in desmoid tumours. Illumina whole genome gene expression BeadChips were used to measure gene expression in FAP adenomas and desmoid tumours. Similarities between gene expression profiles and mechanisms important in regulating formation of FAP adenomas and desmoid tumours were identified. This study furthers our understanding of the mechanisms underlying FAP and desmoid tumour formation.     

Aneurysmal bone cyst of the calcaneum: an expansile locally destructive lesion

Aneurysmal bone cyst (ABC) is a benign but locally destructive lesion affection of which in the calcaneum has rarely been reported in the literature. We report an unusual case of ABC of the calcaneum in a 17-year-old-male, who presented with painful ankle swelling with difficulty in walking. Radiology revealed benign cystic calcaneal lesion, without any evidence of fracture. Biopsy was characterized by formation of osteoid along with the presence of ecstatic blood-filled channels, consistent with ABC. However, this being an uncommon site for ABC, histopathology needs to be used to differentiate it from other benign and malignant entities, and a definitive diagnosis warrants clinical and radiological correlation. Most of the ABCs require surgical curetting and bone engraftment of the surgical defect.     

Periampullary localized pancreatic intraepithelial neoplasia-3 (PanIN-3): evaluation with contrast-enhanced MR cholangiography (MRCP)

Background

The early determination of premalignant lesions of pancreas can prevent unnecessary excessive surgical procedures and can reduce morbidity and mortality. Pancreatic intraepithelial neoplasia-3 (PanIN-3) is a preinvasive form of adenocarcinoma (carcinoma in situ). PanINs have not taken place in the literature of radiology yet, it should be considered in differential diagnosis of pancreatic cystic lesions.

Case report

A patient with preliminary diagnosis of chronic cholecystitis who had choledocolithiasis and periampullary pancreatic cyst detected by noncontrast-enhanced (NCE) and contrast-enhanced (CE) magnetic resonance cholangiography (MRCP) is presented. Pathological examination results of gallbladder and pancreatic cyst were reported as gallbladder adenocarcinoma and PanIN-3, respectively.

Conclusions

Pancreatic cystic lesions with thin septa which enhances slightly with the administration of contrast material may represent PanIN-3. In patients with cystic pancreatic lesion localized at periampullary region, using CE-MRCP together with NCE-MRCP could be useful in the evaluation of pancreatic cystic masses as well as other abdominal pathologies.