High frequency of ��-catenin heterozygous mutations in extra-abdominal fibromatosis: a potential molecular tool for disease management

Background:

Fibromatosis comprises distinct clinical entities, including sporadic extra-abdominal fibromatosis, which have a high tendency for recurrence, even after adequate resection. There are no known molecular biomarkers of local recurrence. We searched for β-catenin mutations in a European multicentre series of fibromatosis tumours to relate β-catenin mutational status to disease outcome.

Methods:

Direct sequencing of exon 3 β-catenin gene was performed for 155 frozen fibromatosis tissues from all topographies. Correlation of outcome with mutation rate and type was performed on the extra-abdominal fibromatosis group (101 patients).

Results:

Mutations of β-catenin were detected in 83% of all cases. Among 101 extra-abdominal fibromatosis, similar mutation rates (87%) were observed, namely T41A (39.5%), S45P (9%), S45F (36.5%), and deletion (2%). None of the clinico-pathological parameters were found to be significantly associated with β-catenin mutational status. With a median follow-up of 62 months, 51 patients relapsed. Five-year recurrence-free survival was significantly worse in β-catenin-mutated tumours regardless of a specific genotype, compared with wild-type tumours (49 vs 75%, respectively, P=0.02).

Conclusion:

A high frequency (87%) of β-catenin mutation hallmarks extra-abdominal fibromatosis from a large multicentric retrospective study. Moreover, wild-type β-catenin seems to be an interesting prognostic marker that might be useful in the therapeutic management of extra-abdominal fibromatosis.     

韧带样型纤维瘤病手术联合放疗疗效观察

目的：观察韧带样纤维瘤病手术联合放疗的疗效。方法：总结我院收治的12例手术联合放疗韧带样纤维瘤病的3年无病生存率。结果：其中位于四肢8例,胸壁2例,腹壁2例。均行手术和术后放疗,手术病理证实为韧带样纤维瘤病,其中波形蛋白阳性10例,阴性2例。术后随访3年,1例复发,其他11例均无病生存,无病生存率83.33%。结论：手术联合放疗可提高韧带样纤维瘤病的无病生存率。     

The role of APC and beta-catenin in the aetiology of aggressive fibromatosis (desmoid tumors)

Background

Aggressive fibromatosis (syn. desmoid tumor) is a sporadically occurring neoplastic proliferation of fibroblasts originating from musculoaponeurotic planes, forming invasively growing masses without the capability to metastasize. The choice of treatment remains surgical resection with or without radiotherapy, and is characterized by high recurrence rates. Better understanding of the aetiology of aggressive fibromatosis is needed to be able to develop new treatment strategies to cope with the high recurrence rates.

Methods

Relevant studies were identified through a search of the electronic databases PubMed/ Medline. The following search terms were used: ‘aggressive fibromatosis’, ‘desmoid tumor’, ‘adenomatous polyposis coli’, ‘APC’, ‘beta-catenin’, ‘Wnt’, ‘Wingless’ and ‘Wnt/Wingless’. Studies were selected for review on the basis of abstract reading. A hand search was performed by checking reference lists in selected articles.

Results

The neoplastic nature of aggressive fibromatosis and the role of the adenomatous polyposis coli (APC) and β-catenin signaling cascade in driving the onset and progression of this disease are discussed.

Conclusion

Mutations in either the APC or β-catenin genes are likely to be a major driving force in the formation of these desmoid tumors. More research is needed to develop new treatment strategies.     

骨促结缔组织增生性纤维瘤的临床病理观察

目的:了解骨促结缔组织增生性纤维瘤的临床病理.方法:收集骨促结缔组织增生性纤维瘤1例和6例腹壁外韧带样纤维瘤病的临床资料.手术切除组织HE染色光镜观察.涂胶切片做Vimentin,Desmin,NF,S100蛋白的单克隆标记.结果:骨促结缔组织增生性纤维瘤的组织学改变和免疫组织化学标记与腹壁外韧带样纤维瘤病相似,临床症状和影像学改变与骨样骨瘤相似.结论:骨促结缔组织增生性纤维瘤易发生于青年男性,病理才能将其确诊,有复发的可能.     

6例深部血管粘液瘤和8例血管肌纤维母细胞瘤临床病理分析

目的探讨深部血管粘液瘤（deep angiomyxoma,DAM）与血管肌纤维母细胞瘤（angiomyofibroblastoma,AMF）的临床病理特点、免疫表型、病理诊断和鉴别诊断要点。方法收集女阴部6例DAM和8例AMF,分析其临床特点,观察病理组织学形态及免疫表型特征,并复习相关文献。结果 6例DAM患者年龄39～56岁,平均48.2岁,8例AMF患者年龄21～50岁,平均40.8岁。14例均表现为真皮深层或皮下缓慢生长肿块,术后随访时间2个月～8年,6例DAM中3例于术后半年到2年复发,8例AMF无复发。组织学上DAM瘤细胞呈弥漫性或结节性分布,丛状分布的血管壁厚薄不均,厚壁血管常玻璃样变性,见＂袖套状＂结构。AMF瘤细胞呈典型的疏密交替,密集区瘤细胞围血管分布,血管小,常为毛细血管,无厚壁血管和＂袖套状＂结构。结论 DAM和AMF均为纤维母-肌纤维母细胞源性肿瘤,好发于女阴部,二者的组织学形态存在重叠,免疫表型也相似,但预后方面存在区别,应予以认识和鉴别。     

A case of juvenile hyaline fibromatosis

Juvenile hyaline fibromatosis (JHF) is a rare, autosomally-recessive disease characterized by papulonodular skin lesions, soft tissue masses, joint contractures, gingival hypertrophy and osteolytic bone lesions. Its onset is in infancy or early childhood. The most commonly affected sites are the nose, chin, ears, scalp, back and knees. The accumulation of an amorphous, hyaline material is typical in the skin and the other organs. Herein, we report a 14-month-old boy who presented with confluent pink papules on the paranasal folds and the chin, and nodular lesions on the periauricular and perianal regions. He had gingival hypertrophy and contractures of the shoulders, knees and elbows. He also had third-degree consanguineous parents. Histopathological studies confirmed the diagnosis of JHF with the presence of increased numbers of fibroblasts embedded in a hyalinized connective tissue stroma.     

A case of bullous pemphigoid arising in juvenile hyaline fibromatosis with oral squamous cell carcinoma

We experienced a case of bullous pemphigoid (BP) arising in juvenile hyaline fibromatosis (JHF) associated with oral squamous cell carcinoma (SCC). JHF is a very rare disease inherited in an autosomal recessive fashion. Skin-colored, elastic hard nodules up to 10 cm in size were scattered mainly on the trunk and scalp. Gingival hypertrophy and an ill-defined mass with an irregular surface on the hard palate were noticed. A skin biopsy and a gingival biopsy confirmed the diagnosis of JFH and oral SCC, respectively. The patient was receiving anti-cancer drugs for the treatment of oral SCC and the treatment was successful. In the meantime, bean to nail sized bullas were noticed on the hands and feet. Histological examination, immunofluorescence method and ELISA confirmed the diagnosis of BP. The pathophysiological mechanisms are discussed in the present case.     

Intracranial aggressive fibromatosis presenting as panhypopituitarism and diabetes insipidus

Aggressive fibromatosis (AF) is a rare, locally aggressive, proliferative fibroblastic lesion affecting musculoaponeurotic structures, most often, of the limbs and trunk. Intracranial AF is extremely rare and requires aggressive treatment to prevent recurrence. We present a case of a 34 year-old male with AF involving intracranial structures causing panhypopituitarism and diabetes insipidus. Patient was admitted to hospital because of polyuria, polydipsia, and loss of libido, impotence, hearing loss, and gait disturbance. On cranial magnetic resonance imaging, the lesion extended through the sphenoid sinus into the both pterygoid recesses, destroying the left lateral wall of the sphenoid sinus and invading the retroorbital area. There was also a distinct lesion in the hypothalamic area. The tumor was markedly isointense on both T2- and T1-weighted images relative to gray matter, and enhanced strongly after administration of gadolinium. The patient underwent partial resection of the lesion via a transcranial approach. The pathological examination of the mass was reported as AF. No other sites were found to be involved by thorax and abdominal tomography. Hormonal assessment of hypothalamic-pituitary dysfunction revealed panhypopituitarism with central diabetes insipidus. Replacement therapy was instituted. In this case, standard treatment of wide-field surgical resection was impossible. On the basis of reports that radiotherapy is an effective treatment for this kind of tumor, we administered radiation to the affected area, since chemotherapy and hormonal treatment of non-resectable tumors are not satisfactory. To our knowledge, this is the first reported case of AF presenting as panhypopituitarism with central diabetes insipidus.     

Desmoid tumor: a case of mistaken identity

Desmoid tumors are rare tumors accounting for only 0.03% of all neoplasms. Mainly occurring in the fourth and fifth decades of life, these tumors originate in musculoaponeurotic tissues of the limbs, neck, trunk, abdominal wall, and mesentery. We present a rare case of a chest wall desmoid tumor that was mistaken for breast cancer on both physical examination and mammography, which highlights the unique risk these tumors present for confusion with other malignant processes. Although past literature contains numerous reports of other misdiagnoses, this case is unique in reporting the potential for misdiagnosis between chest wall desmoid tumors and breast cancer. In cases where suspicious breast findings do not correlate to usual diagnostic measures, such as fine-needle aspiration or core needle biopsy, the possibility of another pathology such as a chest wall desmoid tumor mimicking breast cancer should be considered in the differential diagnosis.