Alessandra Gurrera

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

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.

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

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

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

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.

Hepatic Biliary Adenofibroma: A Hitherto Unrecognized Tumor in Equines. Report of a Case

Hepatic biliary cystadenoma is a well-delineated neoplasm in some domestic animals, especially in cats, but it has not been reported in equines. We report on a case of hepatic biliary tumor, incidentally found in a 10-year-old horse, with gross and microscopic features similar to those observed in biliary adenofibroma of humans. The tumor presented as a solid mass measuring 16 cm in diameter and histologically was composed of complex tubulocystic biliary components embedded in an abundant fibrotic stroma. We regarded this tumor as a morphological variant of biliary cystadenoma of domestic animals. Differential diagnoses from other hepatic biliary tumor-like and tumor lesions are provided.

Verrucous Psoriasis in a Patient with Chronic C Hepatitis Treated with Interferon

There are about 150 million hepatitis C virus week) had been administered for 1 year. This treat(HCV) carriers worldwide, and in industrialised nament had normalised transaminase levels and tions HCV is the cause of 70% of cases of chronic viraemia for about 2 years. HCV RNA follow-up hepatitis.[1] Interferon (IFN)-α, administered either performed about 3 months prior to observation in alone or in association with ribavirin for 6–12 our department revealed relapse (elevated transmonths, has for some time been used to manage aminase levels and viraemia), and further IFNα HCV as it is able to normalise transaminase concenpegylate treatment (80 μg/week subcutaneously) trations and reduce viraemia. However, interferon had been initiated. After 60 days of IFN treatment, treatment is by no means free of side effects, and HCV RNA was negative, but psoriatic onycholysis exacerbation of a latent, or existing psoriasis, which progressively involved the patient’s toeand fingercan at times develop rapidly into a severe condition, nails. has been reported in the literature with its use.[2-4] Physical examination in our department revealed Whether the HCV or IFN is the initiator or exacerdiffuse hyperkeratosis with erythematous-desquabating factor of the psoriatic disease remains to be mative plaques measuring between 1 and 5cm, some established in these cases. of which were aligned along scratch lines (figure 1). We report a case of a man with chronic HCV Lesions were also observed in the major skin folds, receiving IFN treatment where common psoriasis rapidly developed into verrucous psoriasis and an ichthyosis hystrix-like form of psoriasis after 15 days’ of treatment.

Tumour deposits classification in colorectal cancer: is TNM5 better than TNM7?†

We read with great interest the Invited Commentary ‘Evidence-based medicine: the time has come to set standards for staging’ [1] and the Invited Response ‘Evidence-based medicine: the time has come to set standards for staging. Is a radical overhaul really needed?’ [2]. We would like to comment on some controversial issues concerning the classification of tumour deposits (TDs) in colorectal cancer and the utilization of the fifth rather than the seventh edition of the tumour, nodes, metastasis (TNM) classification. Regarding the dimensional criterion used in TNM5 about TD classification, we do not agree with the statement by Quirke et al that ‘advantages were reproducibility and correlating with imaging’ [1]. Size, in fact, is not informative on the histogenesis of TDs. A TD ≤3 mm may be a totally metastatic lymph node; on the contrary, a TD >3 mm may represent vascular invasion with extravascular tumour growth. Therefore we believe that size may not represent a valid criterion to label TD as lymph node metastasis. Goldstein et alshowed that palpable pericolonic TDs, which according to TNM5 should be classified as metastatic lymph nodes, represented perineural, perivascular or intravascular tumour growth and there was no evidence of lymph node metastasis upon step sectioning [3]. In addition, a recent study showed that even small TDs (<2 mm), which should be included in the T-stage according to TNM5, contributed to poor prognosis [4]. Therefore it is crucial not to apply a dimensional or morphological criterion (size and/or shape) to prove which TDs are true metastatic lymph nodes, but to establish whether TDs have a behaviour similar to or more aggressive than that of lymph node metastases. Regarding the statement by Quirke et al [1] about differential diagnosis between TDs and tumour budding (TB), although there is no general consensus about TB definition and quantification, we doubt that pathologists could misdiagnose them as TDs [5]. In a recent study, TB was defined as a single or a group of <5 detached tumour cells at the invasive tumour front [6]. On the contrary, TDs are defined in TNM7 as “discrete foci of tumour found in the pericolic or perirectal fat or in adjacent mesentery (mesocolic fat) away from the leading edge of the tumour, showing no evidence of residual lymph node tissue but within the lymph drainage area of primary carcinoma . . .” [7,8]. In our opinion, the difference between the two types of lesions is evident. We agree with Quirke et al that TD definition after radio-chemotherapy was not addressed in TMN7 [1]. However, this issue was not resolved even in TNM5. Regarding TNM7, it is unclear why TDs should be classified as N1c in otherwise node-negative cases of T1–T2 colorectal cancer, similarly with TNM staging of skin melanoma [2,7]. There is no clinical or biological evidence indicating why satellite nodules found in melanoma and TDs found in colorectal cancer should be considered similar lesions. It is also unclear why the interpretation of TDs in T3–T4 colorectal cancer is left to the individual pathologist, reverting to TNM4 staging, although recent data show that all patients with TDs have a prognosis similar to or even worse than that of patients with nodal metastases [3,4,9]. Ueno et al, using the Akaike Information Criteria, showed that the best prognostic model predictive of survival outcome is obtained by including extravascular TDs in the N-stage and intravascular TDs in the T-staging [9]. If these data were to be confirmed, then all TDs should be included in the N-stage, regardless of T-stage, size and shape, except for TDs defined as ‘vascular type’ or intravascular TDs, which, in our opinion, would be better classified as extramural vascular (lymphatic or venous) invasion [10]. Despite this critical analysis of TNM7, we believe that the use of this edition is mandatory because there is no evidence that TNM5 is better than TNM7. In addition, N-stage should not be based on the personal decision of a pathologist to adhere to TNM5 or TNM7 because the use of two different classifications creates poor reproducibility and stage migration. In daily practice, we believe that TDs should be included in the pathology report, specifying their total number, size (the largest diameter if there are multiple lesions), and association, or not, with large vessels and/or nerves, in order to create more homogeneous groups of patients for enrolment in clinical trials [5,11]. This is crucial to better define the actual prevalence and clinical implication of TDs.

Unclassified pediatric renal stromal tumor overlapping with metanephric stromal tumor and solitary fibrous tumor with diffuse S-100 protein expression.

Metanephric stromal tumor (MST) is a rare pediatric neoplasm unique to the kidneys that is currently included in the spectrum of metanephric tumors, along with metanephric adenoma and adenofibroma. We herein report an unusual case of pediatric renal stromal tumor overlapping with MST and solitary fibrous tumor (SFT). Histologically, the tumor was composed of bland-looking spindle to stellate cells embedded in a fibro-sclerotic stroma that focally surrounded native entrapped renal tubules or blood vessels with abortive rings or collarettes. Alternating hypercellular and hypocellular areas and a focal hemangiopericytomatous-like vascular pattern imparted to the tumor a resemblance to SFT. Angiodysplasia of intratumoral arterioles was also observed, but juxtaglomerular cell hyperplasia was not a feature. Immunohistochemically, the neoplastic cells showed a polyphenotypic profile, including diffuse expression of vimentin and CD34, and focal immunoreactivity for alpha-smooth muscle actin, EMA, and CD99. However, the most striking finding was diffuse nuclear and cytoplasmic expression of S-100 protein. Although this protein has been reported to stain the heterologous glial and/or cartilaginous components that can be occasionally encountered in MST, this marker has not been previously reported in the fibroblastic component of MST. Pathologist should be aware of similar unusual unclassified tumors to avoid potential confusion with other benign or malignant S-100 protein-positive tumors.