Tumors of the liver and intrahepatic bile ducts

OBJECTIVES The RTI International-University of North Carolina at Chapel Hill Evidence-based Practice Center (RTI-UNC EPC) systematically updated evidence on the management of uterine fibroids, specifically incidence and prevalence of fibroids, treatment outcomes, comparisons of treatment, modifiers of outcomes, and costs. DATA SOURCES We searched MEDLINE(R), Cochrane Collaboration resources, and Embase. REVIEW METHODS We included studies published in English from February 2000 through August 2006. We excluded studies with low sample size (based on study design, cases series < 100 and cohorts < 40) or lack of relevance to uterine fibroids. Of 107 included studies, 3 were good quality, 56 fair, and 48 poor. RESULTS The cumulative incidence by age 50 is 70 percent to 80 percent; black women are more likely to get fibroids at younger ages. Appearance of new fibroids and growth of existing fibroids after treatment are poorly studied. Trials of preoperative medical management indicate that treatment reduces fibroid volume but do not provide sufficient evidence of improvement in important operative outcomes. When women are treated for reasons other than symptom relief, such as when pregnancy is desired, weak evidence supports treating submucous fibroids via hysteroscopy. No well-conducted trials in U.S. populations directly compared treatment options, including the option of expectant management, or followed women to determine whether the intervention met their treatment objectives. Common procedures such as hysterectomy and myomectomy, including choice among types of myomectomy, still cannot be meaningfully compared. Studies comparing uterine artery embolization (UAE) with other procedures reported procedure time and length of stay favoring UAE, but inconsistency of the direction of effect for complications and absence of key information on longer-term outcomes suggest that this evidence base is inadequate to comment on the relative risks and benefits of UAE versus hysterectomy or myomectomy. Costs of fibroid treatment, despite shorter average lengths of stay, are rising. CONCLUSIONS The dearth of high-quality evidence supporting the effectiveness of most interventions for uterine fibroids is remarkable, given how common this problem is. The current state of the literature does not permit definitive conclusions about benefit, harm, or relative costs to help guide women's choices. Significant research gaps include well-conducted trials in U.S. populations that directly compare interventions on short- and, especially, long-term outcomes, studies on therapeutics for medical management, and information on treatment decisions for women who desire a pregnancy.

Management of uterine fibroids: an update of the evidence.

Abstract Context.—Myofibroblastoma (MFB) of the breast is an unusual benign tumor that belongs to the family of the “benign spindle cell tumors of the mammary stroma.” The name MFB reflects its cellular composition, comprising mainly stromal cells with fibromyofibroblastic and, less frequently, myoid differentiation. Since the original description, the morphologic spectrum of MFB has been expanded by the recognition of several unusual morphologic variants, such as the cellular, infiltrative, epithelioid, deciduoid-like, lipomatous, collagenized/fibrous, and myxoid variants. Objective.—To review the literature on mammary MFB, discussing the main clinical, radiologic, and pathologic features helpful for diagnosis. Since MFB may show alarming morphologic features, which can lead to a misdiagnosis of malignancy, histologic figures of this tumor, including its more unusual variants, are provided to offer pathologists a practical approach to a correct diagnosis. Histogenesis and pathogenesis of this tumor are also proposed. Data Sources.—Clinicopathologic data on MFB were extracted from all identified articles through PUB Medline– based research. Histologic figures have been taken from the personal archive of the author. Conclusions.—The incidence of MFB diagnosis has increased in recent years, likely due to the mammographic screening. Accordingly, this unusual benign tumor may represent a potential diagnostic pitfall, especially when interpreting fine-needle aspiration and/or needle core biopsy. Pathologists should be aware of the wide morphologic spectrum exhibited by MFB to avoid a misdiagnosis of malignancy. 

Mammary Myofibroblastoma: A Tumor With a Wide Morphologic Spectrum

Distinguishing between epithelioid peritoneal mesothelioma and papillary serous carcinomas involving the peritoneum may be very difficult, owing to overlapping morphologic features. Immunohistochemistry may facilitate establishing a correct diagnosis, but, as no single antibody has demonstrated absolute sensitivity and specificity for either mesothelioma or serous carcinoma, the differential diagnosis is based mainly on the combined use of several markers. The purpose of this study was to ascertain the sensitivity and specificity of a series of mesothelial markers [including more recently investigated antigens such as h-caldesmon (h-CD) and D2-40] and, using receiver operating characteristic curve analysis, to identify a selected appropriate panel of antibodies for differentiating between epithelioid peritoneal mesothelioma and serous papillary carcinoma of the ovary. Fifteen cases of epithelioid peritoneal mesothelioma and 40 cases of papillary serous carcinoma of the ovary (25 primary and 15 metastatic to the peritoneum) were immunostained for h-CD, D2-40, calretinin, cytokeratin 5/6, thrombomodulin, estrogen and progesterone receptors (ER and PR), Ber-EP4, B72.3, CA19-9, and CD15. h-CD and calretinin showed the highest sensitivity (100%), followed by D2-40 (93.3%) and cytokeratin 5/6 (93.3%); thrombomodulin had the lowest sensitivity (60%). h-CD and thrombomodulin had the best specificity (95%) for mesothelioma, followed by calretinin (87.5%), D2-40 (80%), and cytokeratin 5/6 (72.5%). Among carcinoma markers, ER and Ber-EP4 demonstrated the highest sensitivity (95%) followed by B72.3 (72.5%), PR (65%), CA19.9 (60%), and CD15 (45%). The specificity of the nonmesothelial markers was 100%, except for Ber-EP4 (93.3%). The relationship between the values of sensitivity and specificity of each marker using receiver operating characteristic analysis permitted the identification of h-CD, calretinin, ER, and Ber-EP4 as the markers with the best performance in differentiating epithelioid peritoneal mesothelioma from serous papillary carcinoma of the ovary.

h-caldesmon, calretinin, estrogen receptor, and Ber-EP4: a useful combination of immunohistochemical markers for differentiating epithelioid peritoneal mesothelioma from serous papillary carcinoma of the ovary.

Perivascular wall tumors (PWTs) are defined as neoplasms deriving from mural cells of blood vessels, excluding the endothelial lining. The spectrum of human cutaneous PWT includes glomus tumor, hemangiopericytoma (HEP), myopericytoma, angioleiomyoma/sarcoma, angiomyofibroblastoma, and angiofibroma. The purpose of this study was to revise clinical presentation, cytology, histopathology, and immunohistology of canine cutaneous PWT with cytology typical of canine HEP. Diagnosis was established on the basis of vascular growth patterns (staghorn, placentoid, perivascular whorling, bundles from media) and immunohistology, including 7 smooth muscle markers and the cell membrane ganglioside of unknown origin recognized by the antibody 3G5 (CMG-3G5). Twenty cases were included. Ages ranged from 6 to 13 years; 12 dogs were males and 8 were females, and there was a prevalence of crossbreeds. Tumors arose from a single site with preferential acral location (10/20). Cytology revealed moderate to high cellularity in all cases, cohesive groups of cells (19/20), capillaries (18/20), and bi- to multinucleated cells (18/20). Six myopericytomas, 5 angioleiomyomas, 2 angioleiomyosarcomas, 2 HEP, 1 angiofibroma, and 1 adventitial tumor were identified. A definitive diagnosis was not possible in 3 cases. Smoothelin, heavy caldesmon, desmin, myosin, calponin, and CMG-3G5 were the most valuable markers to differentially diagnose canine PWT. Similar to reports in humans, canine HEP embodied a spectrum of neoplastic entities arising from different vascular mural cells. Before canine PWTs are assimilated into one prognostic category, a consistent classification and characterization of their biology is necessary. As proposed in humans, HEP should also be considered a diagnosis of exclusion in dogs.

https://journals.sagepub.com/doi/pdf/10.1354/vp.44-5-607

The Spectrum of Canine Cutaneous Perivascular Wall Tumors: Morphologic, Phenotypic and Clinical Characterization

Aims: The ultrastructural detection of leiomyomatous rather than myofibroblastic features in some cases of myofibroblastoma of the breast led some electron microscopically orientated pathologists to doubt the commonly accepted myofibroblastic nature of such a tumour, so the alternative terms ‘myogenic stromal tumour’ or ‘variant of leiomyoma’ have been proposed. The aim of this study was to analyse the immunohistochemical expression of h-caldesmon, a reliable marker in distinguishing smooth muscle versus myofibroblastic cellular differentiation, in a large series of myofibroblastomas of the breast to clarify whether these tumours are basically leiomyomatous. Moreover, cases from primary myofibroblastic lesions of the breast, such as fibromatosis and inflammatory myofibroblastic tumour, were analysed to assess whether h-caldesmon expression parallels that observed in their soft tissue counterparts.



Methods and results:  Paraffin-embedded sections from 12 cases of myofibroblastoma, seven cases of fibromatosis, and one case of inflammatory myofibroblastic tumour were evaluated immunocytochemically for the expression of h-caldesmon. As expected, all myofibroblastic lesions failed to express h-caldesmon. Conversely, focal staining, ranging from 2% to 10% of neoplastic cells, was detected in myofibroblastomas, even though it was restricted to 50% of analysed cases.



Conclusions:  Our results, indicating that smooth muscle differentiation occurs in a minority of the myofibroblastoma cells exclusively in half of the analysed cases, support the separation of myofibroblastoma from leiomyoma. The detection of smooth muscle cells in breast myofibroblastoma is easily explained if we postulate its histogenesis from the CD34+ fibroblasts of mammary stroma capable of multidirectional mesenchymal differentiation, including smooth muscle. We recommend retention of the term myofibroblastoma for all the desmin-positive and/or α-smooth muscle actin-positive spindle cell tumours of the breast consistent with the previously well-established morphological criteria for such neoplasms, unless one is dealing with a typical leiomyoma easily recognizable at light microscopy.

H-caldesmon expression in myofibroblastoma of the breast: evidence supporting the distinction from leiomyoma.

We describe the clinical, radiological and pathological features of a series of six cases of primary fibromatosis of the breast. Most patients (5 of 6) were women of 22-58 years of age; one case occurred in a 47-year-old man. The fibromatosis of the breast in all cases presented as a monolateral solid nodule, clinically suspicious for malignancy and in three cases was also associated with cutaneous and/or nipple retraction. None of the patients was affected by any genetic disorder characterized by fibromatoses involving multiple sites, including breast. Both echographic and mammographic examinations revealed solid masses with irregular margins but without calcifications, mimicking scirrhous carcinoma. All cases were surgically treated by lumpectomy (4 of 6) or quadrantectomy (2 of 6), and after a follow-up period ranging from 5 months to 13 years all patients are well and disease-free. Histological examination revealed finger-like infiltrating margins entrapping adjacent breast parenchyma and adipose tissue in all cases. The hallmark of the lesion was the presence of bland-looking spindle cells, with a low mitotic index, organized in long sweeping and intersecting fascicles. Three different morphological phases (i.e. proliferative, involutional and residual), identical to those observed in Dupuytren's superficial fibromatosis, variably coexisted in each case. At immunohistochemistry the cells which comprised the lesion exhibited a diffuse expression of vimentin and a heterogeneous immunoreactivity to a-smooth muscle actin, thus confirming their fibro-myofibroblastic nature. No expression of estrogen, progesterone or androgen receptors or of pS2 correlated-estrogen protein was observed. We discuss both the pathogenesis of the mammary fibromatosis, pointing to the fibroblastic cells of the mammary stroma as the putative precursors, and the differential diagnosis versus the bland-looking, monomorphic spindle cell tumor-like or tumorous lesions of the breast.

[Fibromatosis of the breast: a clinical, radiological and pathological study of 6 cases].

Sir, Myofibroblastoma of the breast is an unusual benign mesenchymal tumour that belongs to the family of the socalled benign spindle cell tumours of the mammary stroma [5, 6]. In its classic type, it is typically composed of bland-looking spindle cells exhibiting a variable fibro– myofibroblastic differentiation [5, 6]. In recent years, the morphological spectrum of this tumour has been broadened by the recognition of several variants, including epithelioid, lipomatous, fibromatosis-like, fibrous/collagenized, myxoid ones [4–6]. Recently, we have encountered two cases of mammary myofibroblastoma with atypical cells embedded within a prominent myxoid stroma. To the best of our knowledge, this unusual morphological variant has not hitherto been reported. Two male patients (63 and 56 years) presented with two nodular breast masses, measuring 3 and 3.5 cm in greatest dimension, respectively, which were surgically excised. Histologically, both surgical samples were represented by unencapsulated mesenchymal tumours with pushing borders, composed of spindle to epithelioid cells, embedded in an abundant myxoid stroma containing isolated thick eosinophilic collagen bands (Figs. 1a and 2a). Myxoid matrix stained positively with Alcian blue at pH 2.5 and negative for periodic acid-Schiff. One tumour was hypocellular (Fig. 1a), while the other one showed alternating hypocellular and moderately cellular areas (Fig. 2a). Neoplastic cells had pale to deeply eosinophilic cytoplasm and round to oval nuclei containing one or two visible nucleoli. In both cases, a significant number of neoplastic cells (50– 60%) exhibited a moderate to severe degree of nuclear pleomorphism (Figs. 1a,b and 2a,b). Some cells were bior multinucleated (Fig. 2b). A minor mature fatty component was scattered throughout both tumours. Mitoses were absent in the hypocellular tumour, while one mitosis per ten high power fields was observed in the other neoplasm. Necrosis was absent. No epithelial component was identified within both tumours. Immunohistochemically, the cells of both cases had a similar profile: diffuse and strong immunoreactivity to vimentin, α-smooth muscle actin and desmin (Fig. 1c), and a variable staining to CD34, bcl-2 protein, CD99, estrogen (ER), progesterone (PR), and androgen (AR) receptors. No immunoreactivity was obtained for pancytokeratin, epithelial membrane antigen, h-caldesmon, calponin, S-100 protein, and human melanoma black-45 (HMB-45). This immunophenotype was consistent with a fibro-myofibroblastic nature of the neoplastic cells. We believe that the tumours herein presented fit within the spectrum of breast myofibroblastoma [5, 6], representing an uncommon morphological variant, for which the descriptive term “myxoid myofibroblastoma with atypical cells” is proposed. The following morphological and immunohistochemical features, typically seen in myofibroblastoma [5, 6], support our opinion: (1) Tumours were “pure mesenchymal lesions” lacking any epithelial component; (2) Tumours had pushing borders; (3) The myxoid extracellular matrix contained thick eosinophilic collagen bands; (4) Neoplastic cells resulted to have a fibroVirchows Arch (2007) 450:483–485 DOI 10.1007/s00428-007-0373-z

Myxoid myofibroblastoma of the breast with atypical cells: a potential diagnostic pitfall

We herein report the clinicopathologic features of a rare case of biliary adenofibroma (BAF) of the liver in a 79-year-old man. Grossly, tumour presented as a well-circumscribed, 5.5-cm mass with a solid and microcystic appearance. Histological examination was typical of biliary adenofibroma, showing a proliferation of variable-sized tubulocystic structures embedded in a moderately cellular fibrous stroma. Immunohistochemistry, revealing immunoreactivity of the epithelial component to cytokeratins 7 and 19, was consistent with a bile duct origin. Notably, the stromal cells had a myofibroblastic profile, showing a diffuse and strong expression of vimentin and α-smooth muscle actin. Differential diagnosis with Von Meyenburg complex, biliary adenoma, biliary cistadenoma, congenital biliary cystsy, and hepatic benign cystic mesothelioma is provided. The occasionally reported expression of p53 in biliary adenofibroma has suggested that this tumour could represent a premalignant lesion. The absence of both cytological atypia and p53 immunoreactivity in our case confirms that BAF is a benign tumour with an indolent clinical behaviour. However, a careful histological examination of BAF is mandatory because malignant transformation of the epithelial component has been documented in two cases.

/pdf/biliary-adenofibroma-of-the-liver-report-of-a-case-and-14z1gdl5kn.pdf

Biliary Adenofibroma of the Liver: Report of a Case and Review of the Literature

Well-differentiated lipoma-like liposarcoma of the caecum.

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