Phyllodes tumours of the breast - differentiating features in core needle biopsy

Tsang A K H, Chan S K, Lam C C F, Lui P C W, Chau H H L, Tan P H & Tse G M
(2011) Histopathology  59 , 600–608 Phyllodes tumours of the breast – differentiating features in core needle biopsy Aims: To investigate the usefulness of histological features in the differentiation of fibroepithelial lesions of the breast (phyllodes tumours and fibroadenomas) in core needle biopsies. Methods and results: Forty‐nine and 69 excision‐proven core biopsies of phyllodes tumours and fibroadenomas, respectively, were evaluated histologically for stromal cellular changes (overall stromal cellularity, variability in stromal cellularity, stromal cell pleomorphism, and mitotic count) and stromal architectural changes (stromal overgrowth, fragmentation of the cores, and fat in stroma). In core needle biopsies of phyllodes tumours, overall stromal cellularity, stromal cell pleomorphism and mitotic count showed good correlation with excisions. In phyllodes tumours, core needle biopsy diagnosis showed increased certainty with increasing degree of malignancy. Core biopsies of phyllodes tumours showed more consistent stromal cellular changes (overall stromal cellularity, variability in stromal cellularity, stromal pleomorphism, and mitotic count) than those of fibroadenomas. These parameters were also useful for differentiation between benign and malignant fibroepithelial lesions. For grading phyllodes tumours, stromal cell pleomorphism and mitotic activity were found to be helpful. Conclusions: In the core biopsy assessment of phyllodes tumours, evaluation of selected histological parameters, particularly those pertaining to stromal cellular changes, is helpful.     

Analysis of the progression of fibroepithelial tumours of the breast by PCR-based clonality assay

Fibroadenoma and phyllodes tumour of the breast are both fibroepithelial tumours. Although progression to epithelial malignancy has been described, the behaviour of most fibroadenomas is benign. Phyllodes tumours, on the other hand, can display locally destructive growth and can even metastasize. A relationship between the two tumours has been suggested in the literature. This study investigated the clonality of both the stroma and the epithelium of these fibroepithelial tumours and attempted to construct a model in which fibroadenoma can progress in both an epithelial and a stromal direction. Fibroadenomas (n=25) and phyllodes tumours (n=12) were selected for analysis. Tissue was microdissected and analysed for clonality using a polymerase chain reaction (PCR)-based assay targeted at an X-linked polymorphic marker, the human androgen receptor gene (HUMARA). Nineteen fibroadenomas and nine phyllodes tumours could be analysed. Normal-appearing epithelium, hyperplastic epithelium, and stroma removed from fibroadenomas were polyclonal. As expected, carcinoma in situ (CIS) removed from four fibroadenomas was monoclonal. Three areas of apparent stromal expansion within fibroadenoma were monoclonal, suggesting stromal progression. Mostly, the stroma of phyllodes tumours was monoclonal and the epithelium polyclonal. In two cases, however, the epithelium seemed to be monoclonal, whereas in three other cases the stromal component was polyclonal. These findings indicate that fibroadenoma can progress in an epithelial direction to CIS and in a stromal direction to phyllodes tumour.     

Phyllodes tumours of the breast: a clinicopathological review of thirty-two cases

We have reviewed the histological features and clinical outcome in 32 women with phyllodes tumours of the breast diagnosed in Nottingham between 1975 and 1990. We assessed 23 tumours as histologically benign, four as borderline and five as malignant. After clinical follow up for periods ranging from 36 months to 221 months (median 135 months), six of 23 benign tumours have recurred locally; in all these cases the original tumours had been incompletely excised. There were no recurrences amongst 10 benign tumours in which excision had been complete. Benign tumours which recurred showed a tendency to greater stromal cellularity and more pronounced stromal overgrowth than incompletely excised lesions which did not recur, but these differences were not statistically significant. The recurrent tumours resembled the respective original lesions histologically, except in one case in which two local recurrences were histologically malignant. The recurrent tumours were controlled by further excision or mastectomy in all cases and none have metastasized. All four borderline tumours were completely excised at initial surgery and none have recurred or metastasized. One of the five malignant tumours recurred within two months of incomplete excision, with widespread infiltration of the chest wall, although the patient died of unrelated causes. The other four malignant tumours have not recurred. We conclude that presence of tumour at the margins of the excised specimen is the major determinant of local recurrence in phyllodes tumours and that the histological features are of secondary importance. These findings are discussed in relation to other published series in the literature.     

Recent advances in the pathology of fibroepithelial tumours of the breast

Fibroepithelial lesions of the breast are biphasic lesions with epithelial and stromal components, as exemplified by fibroadenoma and phyllodes tumour. Fibroadenomas are benign, but a subset of complex fibroadenoma is associated with slightly increased long-term cancer risk. Phyllodes tumour is characterised by a leaf-like pattern arising from stromal expansion. It shows a variable degree of malignancy, with a potential for recurrence or metastasis. Conventionally, histological parameters of stromal cellularity, nuclear pleomorphism, overgrowth, mitotic activity and margin configuration are used for grading, but no definitive criteria have been identified to predict the behaviour. Other markers that have been investigated so far include p53, hormonal receptors, proliferation markers, angiogenesis, c-kit (CD117) and CD10 (CALLA), all without clear-cut advantage over histological criteria. There is also emerging histological and molecular evidence that fibroadenoma and phyllodes tumour may be related and epithelial–stromal interaction may play a role in the pathogenesis of these fibroepithelial lesions.     

Fibroepithelial lesions; The WHO spectrum

Fibroepithelial lesions of the breast comprise a morphologically and biologically heterogeneous group of biphasic tumors with epithelial and stromal components that demonstrate widely variable clinical behavior. Fibroadenomas are common benign tumors with a number of histologic variants, most of which pose no diagnostic challenge. Cellular and juvenile fibroadenomas can have overlapping features with phyllodes tumors and should be recognized. Phyllodes tumors constitute a spectrum of lesions with varying clinical behavior and are graded as benign, borderline or malignant based on a set of histologic features according to recommendations by the World Health Organization (WHO). Recent developments have significantly expanded our understanding of the pathogenesis of fibroepithelial lesions, highlighting fibroadenomas as true neoplasms and underscoring a commonality with phyllodes tumors in the form of recurrent MED12 exon 2 mutations. In addition, sequencing studies have elucidated pathways associated with phyllodes tumor progression. Accurate diagnosis and grading of phyllodes tumors are important for patient management and prognosis, as grade broadly correlates with increasing local recurrence risk, and essentially only malignant tumors metastasize. However, classification of fibroepithelial lesions in many cases remains challenging on both core biopsy and excision specimens. A commonly encountered problem at the benign end of the spectrum is the distinction of benign phyllodes tumor from cellular fibroadenoma, which is largely due to the subjective nature of histologic features used in diagnosis and histologic overlap between lesions. Grading is further complicated by the requirement to integrate multiple subjective and ill-defined parameters. On the opposite end of the histologic spectrum, malignant phyllodes tumors must be distinguished from more common metaplastic carcinomas and from primary or metastatic sarcomas, which can be especially difficult in core biopsies. Immunohistochemistry can be useful in the differential diagnosis but should be interpreted with attention to caveats. This review provides an overview and update on the spectrum of fibroepithelial lesions, with special emphasis on common problems and practical issues in diagnosis.     

Mediastinal neuroendocrine tumours

The spectrum of neuroendocrine tumours that may arise in the mediastinal compartment is as varied as their clinical behaviour. Because these tumours may share similar histological features and immunohistochemical profile, it is essential to properly establish a good clinical–radiological and pathological correlation. Some of these tumours by virtue of sharing similar histological features and immunoprofile may be classified into tumours that require more aggressive treatment while in fact they may represent tumours of indolent behaviour in which surgical resection is the treatment of choice. Herein we will review the most salient features of this group of tumours and highlight the important pitfalls in their interpretation, and more importantly their separation into specific entities. In addition, in some of the more aggressive neoplasms, the importance of proper classification is emphasized to provide more meaningful information regarding prognosis and behaviour of the tumour.     

Predictors of phyllodes tumours on core biopsy specimens of fibroepithelial neoplasms

Jara‐Lazaro A R, Akhilesh M, Thike A A, Lui P C‐W, Tse G M‐K & Tan P H
(2010) Histopathology 57 , 220–232 Predictors of phyllodes tumours on core biopsy specimens of fibroepithelial neoplasms Aims: To establish histological and biological parameters that can predict phyllodes tumours on core biopsy specimens of indeterminate fibroepithelial neoplasms. Methods and results: Core biopsy specimens of fibroepithelial lesions diagnosed at the Department of Pathology, Singapore General Hospital from 2002 to 2007 were reviewed. Cases in which phyllodes tumour was favoured, or could not be ruled out, were evaluated for stromal cellularity/distribution, nuclear atypia and mitoses, stromal overgrowth, epithelial fronding, epithelial hyperplasia, configuration of lesional edge, presence of pseudoangiomatous stromal hyperplasia and of adipose tissue. Antibodies to Ki67, topoisomerase IIα, CD34, CD117 and Bcl‐2 were applied to sections subjected to immunohistochemistry using the streptavidin–biotin method. Findings were correlated with subsequent excisions. Of 261 core biopsy specimens of fibroepithelial lesions, 98 (37%) comprised cases in which phyllodes tumour could not be excluded and 57 (58%) had subsequent open surgical excisions. Marked stromal hypercellularity (5/5; 100%) and nuclear atypia (1/1; 100%), stromal overgrowth (17/17; 100%), mitoses ≥2/10 high‐power fields (18/18; 100%) and ill‐defined lesional borders (16/16 phyllodes tumours; 100%) were features in core biopsy specimens that exclusively predicted phyllodes tumour on excision. Moderate stromal hypercellularity (20/27 phyllodes tumours; 74%), stromal overgrowth, moderate nuclear atypia (14/16 phyllodes tumours; 87%), pseudoangiomatous stromal hyperplasia (19/23 phyllodes tumours; 83%) significantly correlated with their subsequent excisions. Immunohistochemical markers Ki67 ≥5% and topoisomerase IIα≥5%, and reduced or patchy CD34 on core biopsy specimens correlated significantly with a diagnosis of phyllodes. Conclusions: Stromal hypercellularity, combined with key histological features and immunohistochemical markers Ki67, topoisomerase IIα and CD34, reinforced by clinical findings, can predict phyllodes tumours on core biopsy specimens.     

Malignant phyllodes tumours show stromal overexpression of c-myc and c-kit

Phyllodes tumours are fibroepithelial neoplasms of the breast, the stroma of which can undergo malignant progression to sarcoma. The frequency of malignant lesions varies in different series from 5% to 30%. The aim of this study was to elucidate potential molecular mechanisms in the progression to malignancy in phyllodes tumours. c-myc and c-kit were studied at the protein, RNA(c-myc only) and DNA level. We chose to study c-myc as we have previously shown that Wnt signalling is important in benign, but not malignant, phyllodes tumours. If c-myc is constitutively activated in malignant tumours, this may provide an explanation for why the Wnt pathway is no longer important in these tumours. c-kit is a membrane-bound tyrosine kinase receptor and overexpression is characteristic of gastrointestinal stromal tumours. A previous report suggested that this may also be the case in malignant phyllodes tumours, and we wished to confirm this. We assessed expression of c-myc and c-kit in 30 phyllodes tumours (10 malignant) using in situ hybridization (c-myc) and immunohistochemistry (c-myc and c-kit). 9/10 malignant tumours showed c-myc expression in the stroma, compared to 7/20 benign tumours (p = 0.006, Fisher's exact test). Stromal c-kit expression was found in 5/10 malignant tumours, compared to 1/20 benign tumours (p = 0.008, Fisher's exact test). One tumour had high-level amplification of c-myc, but we found no evidence of mutations of c-kit. We hypothesize that the overexpression of c-myc may drive stromal proliferation in malignant phyllodes tumours, and that c-kit overexpression contributes to the growth of these lesions. c-kit may also be a new therapeutic target in these tumours.     

乳腺叶状肿瘤的临床病理学研究

目的 探讨乳腺叶状肿瘤的病理形态学特点,分类和诊断标准,与复发转移的关系及其临床意义。方法 采用回顾性分析的方法对203例有随1访（6－372个月）资料的叶状肿瘤作了详细形态学持征的分析和分类研究,统计学聚类判别分析（SPSS软件10．0版）。结果 良性133例（复发28例）,交界性42例（复发19例,死亡2例）,恶性28例（复发18例,死亡15例）。统计学分析结果显示,肿瘤生长方式,瘤细胞异型性,核分裂象计数和肿瘤性坏死所组成的变量子集分类错判率为零。以此4项为主,完善了病理组织学诊断标准。良性,交界笥和恶性组间复发率,转移和死亡率差异均有显著性意义。肿瘤复发随术式的扩大而减少,2次以上复发占53．85％（35／65）。结论 此瘤可分为良性,低度恶性（交界性）及恶性三种类别。肿瘤生长方式,瘤细胞异型性,核分裂象和肿瘤性坏死是诊断此瘤并对其进行分级（分类）的重要依据。提示首次术式的选择的重要性,良性叶状肿瘤应选择肿物扩大切除术,对于复发的交界性和恶性肿瘤应作乳房切除术。     

Altered expression of p53 and its regulated proteins in phyllodes tumours of the breast.

The histological characteristics of phyllodes tumours of the breast are often not related to their clinical outcome. Additional studies must therefore be performed to investigate the possible relationship of cell biological parameters to the biological behaviour of these tumours. The expression of Ki-67, p53, and its regulated proteins has been studied in 19 primary phyllodes tumours, from patients with known follow-up, using immunohistochemical and molecular biological techniques. Overexpression of the p53 protein was observed in four cases and mutation in two cases. In only one case, the sequence alteration, at codon 273, was associated with overexpression of p53 protein and with strong expression of Ki-67 (30 per cent). This alteration was found in the primary, the recurrent, and the metastatic tumour samples. Moreover, the same p53 gene mutation, Arg273Cys, was detected in all tumour samples. No mutation was found in adjacent normal breast tissue, indicating that this was an acquired mutation. Unexpectedly, strong BAX expression was observed in the primary tumour. The patient died during the follow-up period. It is concluded that p53 gene status and an accumulation of BAX, both involved in the same apoptosis-controlling pathway, may be of prognostic relevance in phyllodes tumours.     

Optimising preoperative diagnosis in phyllodes tumour of the breast

The role of the pathologist in the preoperative diagnosis of phyllodes tumours of the breast is critical to appropriate surgical planning. However, reliable differentiation of phyllodes tumour from cellular fibroadenoma remains difficult. Preoperative diagnostic accuracy allows correct surgical treatment, avoiding the pitfalls of reoperation because of inadequate excision, or surgical overtreatment. Specific clinical indices may arouse diagnostic suspicion but are unreliable for confirmation, as with current imaging modes. Fine needle aspiration cytology has a high false negative rate. Few studies have evaluated the role of core needle biopsy, but it may prove a useful adjunct. Both diagnostic and prognostic information may in future be gained from application of immunohistochemical and other techniques assessing the expression of proliferative markers including p53, Ki-67, and others.     

Endothelin-1 expression correlates with atypical histological features in mammary phyllodes tumours

BACKGROUND AND AIMS: Endothelin-1 expression is increased in infiltrating duct carcinoma and is associated with larger tumour size, higher histological grade and lymphovascular permeation. This has not been evaluated in phyllodes tumours, which are uncommon fibroepithelial lesions with potential for local recurrences or distant metastasis. While the grading of phyllodes tumours depends on a combination of histological parameters, prediction of their behaviour remains difficult. METHOD: A large series of 461 phyllodes tumours (291 benign, 115 borderline malignant and 55 frankly malignant) were evaluated for endothelin-1 expression in both the epithelial cells and stromal cells by immunohistochemistry; results were correlated with the tumour grade. RESULTS: For benign phyllodes tumours, the epithelial staining of endothelin was negative, weak, moderate and strong in 6%, 26%, 15% and 53% of cases respectively; results were 4%, 18%, 19% and 59% respectively for borderline and 6%, 18%, 6% and 70% respectively for frankly malignant tumours. For the stromal staining, the negative, weak, moderate and strong staining was 32%, 19%, 18% and 31% respectively for benign phyllodes, 24%, 13%, 10% and 53% respectively for borderline and 8%, 16%, 17% and 59% respectively for frankly malignant tumours. There was correlation between epithelial and stromal staining, and the stromal staining correlated with histological features of stromal cellularity, stromal cell nuclear pleomorphism, margin status and stromal overgrowth. CONCLUSION: These observations suggest a close relationship between the epithelial and stromal elements in phyllodes tumours; endothelin may play a significant role in the malignant progression of phyllodes tumours.     

Malignant phyllodes tumor with heterologous liposarcomatous differentiation and tubular adenoma-like epithelial component

Phyllodes tumor of the breast is a biphasic fibroepithelial neoplasm. A 30-year-old woman presented with a 1-year history of a palpable, asymptomatic right breast mass without axillary lymphadenopathy and family history of breast carcinoma. Malignant phyllodes tumor was diagnosed. The authors present not previously described histological appearance of this tumor where an epithelial component was identical to that of a tubular adenoma of the breast, with the review of the literature. This is in addition to very rare liposarcomatous stromal differentiation in the malignant phyllodes tumor.     

An approach to the diagnosis of spindle cell lesions of the breast

Although most breast spindle cell lesions (BSCLs) are rare, they constitute a wide spectrum of diseases, ranging from reactive processes to aggressive malignant tumours. Despite their varied histogenesis and behaviour, some lesions show an overlap of morphological features, making accurate diagnosis a challenging task, particularly in needle core biopsies. Clinical history and immunohistochemistry can help in making a correct diagnosis in morphologically challenging cases. To make an accurate diagnosis, it is important to maintain a wide differential diagnosis and be familiar with the diverse morphological appearances of these different entities. BSCLs can generally be classified into bland‐looking and malignant‐looking categories. In the former, the commonest diagnosis is scarring. However, it is important to distinguish low‐grade spindle cell metaplastic breast carcinoma from other benign entities, as the management is clearly different. In the malignant category, it is important to differentiate metaplastic carcinoma from other malignant primary and metastatic malignant spindle cell tumours of the breast, such as malignant phyllodes tumour, angiosarcoma, and melanoma. This review focuses on the classification and histological and molecular diagnosis of various BSCLs, with an emphasis on the diagnostic approach, including in core biopsies.     

Reappraisal of the papillary urothelial neoplasm of low malignant potential (PUNLMP)

Although the papillary urothelial neoplasm of low malignant potential (PUNLMP) diagnostic category was retained in the updated 2016 World Health Organisation (WHO) classification of tumours of the urinary system, there still exists a great deal of controversy regarding the biological behaviour of these tumours. We review PUNLMP tumours and histological grading with an emphasis on the histomorphological, genetic and clinical similarities between PUNLMP and low-grade non-invasive papillary urothelial carcinoma. A literature search using PubMed was performed. All relevant literature concerning PUNLMP and the grading of urothelial tumours was reviewed. PUNLMPs cannot be reliably distinguished from low-grade non-invasive papillary urothelial carcinomas based on the histomorphological criteria outlined in the WHO 2004/2016 classification system. PUNLMPs and low-grade non-invasive papillary urothelial carcinomas are not only morphologically similar, but also share similar molecular genetic alterations and a similar risk of recurrence and progression. In addition, there are no consensus recommendations for a different method of treatment and follow-up for these two tumour types. Attempting to distinguish PUNLMP from low-grade papillary urothelial carcinoma adds an unnecessary level of complexity to the grading and classification of urothelial tumours. We feel that PUNLMP terminology should be abandoned and that all such tumours should be classified as low-grade carcinomas until more objective determinants of clinical outcome can be established.     

Phyllodes tumors of the breast segregate in two groups according to genetic criteria.

Phyllodes tumors are rare fibroepithelial tumors of the breast. The pathologic grading of phyllodes tumors based on the aspect of the stromal component, is divided into 2 or 3 grades according to the system used. To determine whether genetic markers could be of use for improving the classification of phyllodes tumors and to provide a better knowledge of the genetic alterations in these tumors, we analyzed chromosomal changes detected by comparative genomic hybridization (CGH) in comparison with histological data, in a series of 30 cases. Recurrent chromosome imbalances were observed in 55, 91 and 100% of benign, borderline and malignant phyllodes tumors, respectively. The mean number of chromosome changes was one in benign, six in borderline, and six in malignant phyllodes tumors. Most frequent genetic imbalances were +1q (12/30), -13q (7/30), -6q (9/30), +5 (9/30) and -10p (8/30). Gains of 1q, present in only one of nine benign tumors, were found in 11/21 (51%) borderline or malignant tumors. Losses of 13q have 13q14.2 as smallest region of overlap, suggesting that the RB1 gene could be the target of deletions. Amplifications of 12q14, involving the MDM2 locus, and of 8p24, involving the MYC gene, were observed in one case each. Borderline and malignant phyllodes tumors could not be differentiated on the basis of their genomic imbalances (presence and number of chromosomal changes, presence of 1q gain and/or 13q loss). Conversely, benign tumors could be significantly differentiated from the group composed of borderline and malignant tumors (P<0.01). This study reveals two distinct patterns of genomic imbalance in phyllodes tumors: benign, with none or a few chromosome changes and malignant, with numerous recurrent chromosomal changes, in particular 1q gain and 13q loss. Helpful additional pathological criteria for differentiating the two genetic groups of phyllodes tumors are the nuclear size and the mitotic rate.     

Concurrent development of testicular seminoma and choriocarcinoma of the superior mediastinum, presented as cervical mass: a case report and implications about pathogenesis of germ-cell tumours

Background

Synchronous presentation of more than one germ cell tumours of different histology in the same patient is considered to be very rare. In these cases of multiple germ cell tumours, strong theoretical and clinical data suggest an underlying common pathogenetic mechanism concerning genetic instability or abnormalities during the pluripotent embryonic differentiation and maturation of the germ cell.

Case presentation

A 25 year-old young man presented with an enlarging, slightly painful left cervical mass. Despite the initial disorientation of the diagnosis to a possible thyroid disorder, the patient underwent complete surgical resection of the mass revealing mediastinal choriocarcinoma. Subsequent ultrasound of the scrotum indicated the presence of a small lobular node in the upper pole of the left testicle and the patient underwent radical left inguinal orchiectomy disclosing a typical seminoma. Based on these results, the patient received 4 cycles of Bleomycin, Etoposide and Platinum chemotherapy experiencing only mild toxicity and resulting in complete ongoing clinical and biochemical remission.

Conclusion

The pathogenesis of concurrent germ cell tumours in the same patient remains an area of controversy. Although the genetic instability of the pluripotent germ cell offers an adequate explanation, the possibility of metastasis from the primary, less differentiated tumour to a distant location as a more mature subtype cannot be excluded. Possible development of a metastatic site of different histology and thus biological behaviour (e.g choriocarcinoma) should be anticipated. Furthermore, urologists, pathologists and medical oncologists should be meticulous in the original pathological diagnosis in these patients, since there is a significant frequency of germ cell tumours with mixed or overlapping histological elements with diverse potential of evolution and differentiation.     

Prognostic factors in anal squamous carcinoma: a multivariate analysis of clinical, pathological and flow cytometric parameters in 235 cases

Clinical, pathological and flow cytometric parameters have been analysed by univariate and multivariate analysis to define those parameters of important prognostic influence in 235 cases of surgically treated squamous carcinoma of the anus and perianal skin. Patients had been treated by anorectal excision (166 patients) or by local excision (69). Analyses were carried out on five data sets--the two surgical subgroups, two groups distinguished by site of tumour and on all 235 patients. Univariate analysis showed many parameters to be of prognostic influence, although histological typing of tumours into the more common histological subtypes was of no prognostic value. Parameters of independent prognostic significance in multivariate analysis were those indicating depth of spread, inguinal lymph node involvement and DNA-ploidy. In this study the subdivision of the rarer types of anal canal tumour, such as mucoepidermoid carcinoma, microcystic squamous carcinoma and small cell anaplastic carcinoma, was relevant confirming that these tumours have a poor prognosis. It is now felt that surgery should not be employed as primary treatment in most cases of anal cancer and the results of this study have to be interpreted with caution when applied to patients treated with radiotherapy with or without chemotherapy. Nevertheless, our findings suggest that the most useful prognostic information can be gleaned from accurate clinical staging and an assessment of DNA-ploidy status.     

Histological features useful in the distinction of phyllodes tumour and fibroadenoma on needle core biopsy of the breast

AIM: To identify features useful in distinguishing phyllodes tumours from fibroadenomas on core biopsy. METHODS AND RESULTS: Starting from the diagnosis made on the surgical specimen, 12 features in the previous core biopsy specimens were analysed. Thirty-six phyllodes tumours had 44 previous core biopsy specimens, which were reported as fibroadenoma in 11 and spindle cell lesion of uncertain nature in one, and included phyllodes tumour in the differential diagnosis in 32. The lesions with a core diagnosis of fibroadenoma were excised largely because they were growing or exceeded 30 mm; review of the corresponding surgical specimen showed heterogeneous stromal cellularity. Thirty-eight fibroadenomas had previous core biopsy specimens reported as fibroadenoma in 37, and one of which included phyllodes tumour in the differential diagnosis. The following four features were significantly more common in cores from phyllodes tumours and had a kappa statistic of > 0.6 in a reproducibility study: stromal cellularity increased in at least 50% compared with typical fibroadenoma, stromal overgrowth (x10 field with no epithelium), fragmentation and adipose tissue within stroma. CONCLUSIONS: This study describes features useful in the diagnosis of phyllodes tumour on core biopsy. Some core biopsy specimens from phyllodes tumours show features of fibroadenoma on core biopsy because of tumour heterogeneity.     

The histopathological grading of soft tissue tumours: current concepts

Malignant tumours of soft tissue (sarcomas) represent a heterogeneous group of neoplasms which differ widely in their potential clinico-biological behaviour, ranging from lesions with an indolent clinical course to lesions that behave in a highly aggressive manner. While certain tumours exhibit fairly consistent and predictable histotype-specific behaviour (underscoring the importance of accurate histopathological classification), other lesions have a broad range of clinical behaviour not immediately predictable from histological typing alone. Due to the relative rarity of malignant soft tissue tumours, studying and comparing large groups of individual tumour types is problematic. Consequently, the identification of histotype-specific parameters that may influence and/or predict clinical behaviour remains difficult, limiting knowledge about possible prognostic parameters for many of the rarer sarcomas. Histopathological grading of sarcomas as a general group represents an attempt to identify histotype-independent histological parameters that may be of use in predicting prognosis. Specifically, this is primarily applicable to those tumour types which exhibit a broad range of biological behaviour, newer tumour entities with an as yet uncertain longer term clinical course, unclassifiable lesions, and lesions about which there is diagnostic disagreement. Histopathological grading has direct clinical application in the design of prospective clinical trials to compare the clinical outcome of various management protocols and hence select optimal treatment strategies. The two best established and most widely used grading schemes are the ‘National Cancer Institute’ and the ‘Fédération Nationale des Centres de Lutte Contre le Cancer’ systems. Despite its limitations, histopathological grading appears to be effective in predicting distant metastasis as well as overall survival. Recent studies are beginning to indicate that genetic variability within certain tumour groups may be of prognostic value, potentially facilitating efforts at prognostication for certain tumour types/subtypes.