Malignant phyllodes tumor of the breast with predominant chondrosarcomatous differentiation

Malignant phyllodes tumor of the breast is a rare biphasic neoplasm, the stromal component of which may show homologous and heterologous sarcomatous elements. We present a case of a histologically malignant phyllodes tumor with sarcomatous overgrowth, affecting a 37-year-old woman in whom a chondrosarcomatous component constituted over 80% of the tumor volume. A malignant phyllodes tumor displaying a predominant chondrosarcomatous component is indeed rare, and the differential diagnosis could well affect the therapeutic approach, mainly with regard to metaplastic carcinoma and primary chondrosarcoma of the mammary gland. Thus, it is important to sample the tumor thoroughly to detect the presence of any area of typical phyllodes tumor, which could be very small. Immunohistochemical stains also should be performed so as to exclude a malignant epithelial component. After the final morphological diagnosis, our patient underwent a complete mastectomy without axillary disection. One year later, no local recurrence or metastasis was apparent.     

The coexistence of invasive ductal carcinoma and malignant phyllodes tumor with liposarcomatous and chondrosarcomatous differentiation in the same breast in a post-osteosarcoma case

Malignant phyllodes tumors of the breast are rare biphasic neoplasms, the stromal component of which may show homologous and heterologous sarcomatous elements. Malignant epithelial transformation is rare. It has been reported in a few cases of in situ and infiltrating ductal or lobular carcinoma. Rarely, breast carcinomas and phyllodes tumors may also develop in the same breast independent of each other. To our knowledge, this is the first case of two different types of tumor occurring in the same breast at the same time in a post-osteosarcoma case.     

Immunohistochemical study of hormone receptor and hormone-regulated protein expression in phyllodes tumour: comparison with fibroadenoma

 The histogenesis of phyllodes tumour (PT) and that of fibroadenoma (FA) of the breast appear to be closely related. FA is thought to be hormonally responsive, while the hormone-responsiveness of PT is uncertain. To gain insight into hormone-responsiveness of PT, we performed immunohistochemical analysis of oestrogen-regulated pS2 and androgen-regulated prostate-specific antigen (PSA) protein expression and also of oestrogen receptor (ER), progesterone receptor (PgR) and androgen receptor (AR) expression in paraffin sections obtained from 50 female PT patients. Paraffin sections taken from 50 female fibroadenoma (FA) patients were analysed for comparison. ER, PgR, pS2, AR and PSA expression were detected in 32%, 96%, 20% 98% and 4.0% of PT sections and in 28%, 96%, 42% 80% and 10% of FA sections, respectively. No correlations were detected among ER, PgR and pS2 expression or between AR and PSA expression in PT or FA sections. PgR expression was significantly associated with AR expression in PT (P<0.0001). The present investigations indicate that PT and FA have almost similar hormone receptor status. However, different positivities of pS2 expression suggest that oestrogen-responsiveness may differ between PT and FA. In addition, a wide-ranging co-expression of AR and PgR in PT sections suggests that these receptors may play an important part in the proliferation, although the functional significance of these receptors should be elucidated. Received: 26 January 1998 / Accepted: 5 April 1998     

Recent developments in the histological diagnosis of spindle cell carcinoma, fibromatosis and phyllodes tumour of the breast

This article reviews recent advances in the diagnosis of these three unusual tumours of the breast. Spindle cell carcinoma needs to be considered in the differential diagnosis of many mammary spindle cell lesions: it is important to be aware of the wide range of appearances, including the recently described fibromatosis-like variant. Immunohistochemistry using a broad panel of cytokeratin antibodies is needed to exclude spindle cell carcinoma; there is frequent expression of basal cytokeratins and p63. CD34 is often expressed by the stroma of phyllodes tumours, but does not appear to be expressed by spindle cell carcinoma or fibromatosis. Nuclear β-catenin is found in about 80% of fibromatoses, but can also be seen in spindle cell carcinomas and phyllodes tumours. Two recent studies have described features useful in the distinction of phyllodes tumour and fibroadenoma on core biopsy, including increased cellularity, mitoses and overgrowth of the stroma, adipose tissue in the stroma and fragmentation of the biopsy specimen. Periductal stromal tumour is a recently described biphasic tumour composed of spindle cells around open tubules or ducts (but no leaf-like architecture) with frequent CD34 expression. The overlap of morphology with phyllodes tumour suggests that it may be best regarded as a variant of phyllodes tumour.     

乳腺浸润性导管癌与小叶癌的超声诊断分析

目的探讨乳腺浸润性导管癌和浸润性小叶癌的超声声像图特征。方法对2006年1月至2008年6月经手术、病理证实为乳腺浸润性导管癌（IDC）136例和浸润性小叶癌61例的超声声像图、彩色多普勒表现进行对比分析。结果两种病理类型的肿瘤的超声声像图在肿块形状、内部与后方回声以及血流图上差异有统计学意义（P〈0．05）。在侧方回声与内部钙化情况上差异无统计学意义（P〉0．05）。结论乳腺浸润性导管癌和浸润性小叶癌可以根据各自超声声像的特点进行诊断，组织学的不同影响乳腺癌的超声影像表现。     

Malignant ovarian mixed germ cell tumour: a rare combination

Ovarian germ cell tumours are very rare and affect mainly young girls and women. Due to this, the conservation of reproductive potential is of great concern. One of the most remarkable advances in oncology is in the treatment of malignant ovarian germ cell tumours. Two histological groups are distinguished: dygerminomas, equivalent to testicular seminomas, and non-dysgerminomatous tumours. We report a case of a 30-year-old nulliparous woman who presented with persistent per vaginal bleeding and was found to have a malignant mixed germ cell tumour comprising of both embryonal carcinoma and choriocarcinoma.     

p16 and pRb immunohistochemical expression increases with increasing tumour grade in mammary phyllodes tumours

Karim R Z, Gerega S K, Yang Y H, Spillane A, Carmalt H, Scolyer R A & Lee C S
(2010) Histopathology 56, 868–875
p16 and pRb immunohistochemical expression increases with increasing tumour grade in mammary phyllodes tumours Aims: Control of cell cycling and proliferation is critical to the development of neoplasia and may play a role in the pathogenesis of phyllodes tumours (PTs). This study aimed to evaluate the immunohistochemical expression of certain proteins from the G₁/S transition of the cell cycle in a cohort of PTs, to determine their role in tumour pathogenesis and to identify any associations with patient outcome. Methods and results: Sixty‐five PTs (34 benign, 23 borderline and eight malignant) diagnosed at a single institution between 1990 and 2006 were analysed. Immunohistochemistry for p16, pRb, cyclin D1 and Ki67 was performed. Expression of the following markers increased significantly with tumour grade: stromal nuclear and cytoplasmic p16 (P = 0.01 and 0.002, respectively), stromal and epithelial pRb (P = 0.000 000 06 and 0.004, respectively), and stromal and epithelial Ki67 (P = 0.03 and 0.04, respectively). Epithelial pRb scores of 7 (range 0–7) were significantly associated with reduced disease‐free survival (DFS) compared with scores of <7 (P = 0.0009). No relationship was found between cyclin D1 expression in either the epithelium or the stroma, and grade or DFS. Conclusions: The results suggest that alterations at the G₁/S transition of the cell cycle play an important role in the progression of PTs.     

CD24 expression in ductal carcinoma in situ and invasive ductal carcinoma of breast: an immunohistochemistry-based pilot study

CD24 is a small, heavily glycosylated cell surface protein, that is expressed in a large variety of solid tumors. It is considered to play an important role in tumor progression and metastasis. We aimed to evaluate CD24 expression in invasive ductal carcinomas (IDCa), ductal carcinoma in situ (DCIS) and non-tumorous breast tissues, and to investigate the relationship between histopathological parameters, estrogen and progesterone receptors, and c-erbB2 expressions. The study included 34 IDCa, 25 DCIS, and 13 non-tumorous breast tissues. All cases were reevaluated histopathologically, and immunohistochemistry was performed with monoclonal CD24 antibody. The results clearly demonstrated that CD24 expression, including membranous and cytoplasmic staining, was significantly higher in DCIS and IDCa than in the non-tumorous breast (p=0.001, p=0.000, and p=0.035, p=0.000, respectively). Cytoplasmic staining was detected predominantly in neoplastic tissues and was significantly increased in high grade DCIS (p=0.013). In invasive carcinomas, although the level of membranous staining was significantly positively correlated with tumor grade (p=0.040), there was no such an association with the cytoplasmic level. However, it showed a trend towards pT (p=0.089). In conclusion, our results suggest that higher CD24 expression may be associated with malignant transformation and progression in breast cancer biology. Furthermore, higher membranous expression and, in particular, cytoplasmic staining seem to predict malignant transformation, and different patterns of CD24 expression may be associated with different pathological features in breast tumors.     

Malignant myoepithelioma of the breast metastasizing to the jaw

A breast tumor in a 52-year-old female was interpreted as a malignant myoepithelioma based on morphological and immunohistochemical studies. The tumor consisted of elongated cells with clear cytoplasm and lacked glandular components. The tumor cells were stained positively for keratin, S-100 protein, glial fibrillary acidic protein (GFAP) and muscle-specific actin. Distant metastasis in the right jaw developed 8 years after the initial surgery and the metastatic deposit showed a similar morphology and immunoreactivity. Myoepithelial tumors are generally considered as benign or low-grade lesions and distant metastasis has been rarely documented. The present case presents the possibility of delayed occurrence of distant metastasis in myoepithelial tumor of the breast. Received: 22 January 1999 / Accepted: 18 May 1999     

Intracranial germ cell tumour (embryonal carcinoma with teratoma) with complex karyotype including isochromosome 12p

 We report the chromosomal characteristics of a malignant teratoma with embryonal carcinoma component located in the pineal region of a 15-year-old boy. Chromosome analysis showed a near-triploid complex karyotype (62 chromosomes), including two copies of an isochromosome 12p, confirmed by fluorescence in situ hybridization analysis. The present findings indicate that isochromosome 12p formation is probably associated with the development of malignant germ cell tumours. Received: 24 February 1998 / Accepted: 15 July 1998     

Coexistent adenomyoepithelioma and invasive ductal carcinoma of the breast: presentation as separate tumors

Adenomyoepitheliomas are rare breast tumors. We report an unusual case of adenomyoepithelioma associated with invasive ductal carcinoma here. Histologically, the lesion consisted of two separate tumors. One nodule corresponded to invasive ductal carcinoma consisting of tubular and trabecular arrangements of columnar or cuboidal neoplastic cells. The other tumor corresponded to adenomyoepithelioma consisting of an inner layer of neoplastic cells with basophilic cytoplasm and the outer layer of neoplastic cells with clear cytoplasm. Immunohistochemically, some myofibroblasts were observed in the stroma of both adenomyoepithelioma and invasive ductal carcinoma, but no CD34-positive stromal cells were seen in the stroma of either lesion. The stromal reaction of adenomyoepithelioma resembles that of intraductal papilloma in the previous study. To the best of our knowledge, this is the first case of coexistent adenomyoepithelioma and invasive ductal carcinoma of the breast that were discovered as separate nodules. Clinicians and pathologists should be aware of such an association because they need to distinguish such a case from malignant neoplasms arising in adenomyoepithelioma. Additionally, our preliminary report suggests that the stromal response of adenomyoepithelioma may resemble that of intraductal papilloma.     

Tenascin C is a prognostic determinant and potential cancer-associated fibroblasts marker for breast ductal carcinoma

Tenascin C (TNC) is a key of extracellular matrix glycoprotein and highly express in numerous human malignancies. Herein, we attempted to clarify the clinicopathological significance of TNC as a prognostic determinant of breast ductal carcinoma. Then, we investigated TNC immunohistochemical expression in 150 breast ductal carcinomas and 27 normal breast tissue samples. Clinical relevance of TNC expression and the association TNC expression with other factors related to cancer-associated fibroblasts were also examined. In results, TNC expression was significantly higher in breast ductal carcinoma (56.0%) than normal breast tissues (25.9%). The upregulation TNC in cancer stromal were associated with pT stage (P = 0.003), lymph node metastasis (P = 0.002) and tumor node metastasis stage (P = 0.001), also was correlated with an increase in tumor-associated macrophage population (P < 0.001). The microvessel density (MVD) was significantly higher in TNC positive group than in negative group (P < 0.001). In both univariate and multivariate Cox regression analyses, TNC was an independent poor prognostic factor for overall survival (OS) in breast ductal carcinoma patients. Importantly, over-expression TNC (P < 0.001), FSP1 (P < 0.001), SMA (P = 0.002) and Vimentin (P = 0.049) were significantly correlation with the lower OS (P < 0.005). In addition, TNC expression in breast ductal carcinoma stromal was positively correlated with FSP1 (P < 0.001), SMA (P = 0.001) and Vimentin (P < 0.001). In conclusion, the high expression of TNC could be a useful cancer-associated fibroblasts marker for the prediction of prognosis of breast ductal carcinoma patients.     

Atypical cystic lobules: an early stage in the formation of low-grade ductal carcinoma in situ

Evidence from many studies has established the neoplastic potential of ductal carcinoma in situ, but the origin and the morphological characteristics of the early stages of this proliferation remain unidentified. Workers writing in the early twentieth century observed a cystic transformation of lobules and proposed that it represented one such early stage, and contemporary European and Japanese pathologists have reached the same conclusion. We describe the characteristics of this cystic transformation, which we call us “atypical cystic lobules,” and present evidence to support the proposal that the alteration is a step in the formation of low-grade ductal carcinoma in situ. Atypical cystic lobules are a proliferation of luminal cells showing low-grade cytological atypia without architectural atypia. The study group comprised 21 cases of atypical cystic lobules from specimens also showing conventional low-grade ductal carcinoma in situ or lobular neoplasia. Immunohistochemical staining for hormone receptors, keratin 19, and cyclin D1 revealed that atypical cystic lobules demonstrated a consistent immunophenotype, which differs from the pattern shown by normal lobules and benign lesions and matches that of low-grade ductal carcinoma in situ. In about 40% of the cases, atypical cystic lobules merged with fully established micropapillary/cribriform ductal carcinoma in situ. The similarities in the cytological and immunohistochemical features and the proximity of the two types of proliferation suggest that atypical cystic lobules represent an early stage in the formation of certain types of low-grade ductal carcinoma in situ. Received: 5 February 1999 / Accepted: 24 March 1999     

Loss of heterozygosity in ductal carcinoma in situ of the breast

Loss of heterozygosity (LOH) at loci reported to show allele loss in invasive breast cancers was examined in ductal in situ carcinomas of the breast using polymorphic short tandem repeats and the polymerase chain reaction (PCR). LOH was detected at all loci examined in at least 11 per cent of the samples examined. The proportion of cases of in situ carcinoma showing LOH at these loci was similar to that previously reported in invasive cancers. Cases of pure in situ cancer without an invasive component exhibited an overall lower frequency of allele loss. LOH at more than one locus was observed in some intraductal cancers. In a small number of cases, LOH was present in the invasive but not in the intraductal component of the tumour, suggesting that mutation at the locus concerned was associated with development of invasive behaviour.     

Solid papillary ductal carcinoma in situ versus usual ductal hyperplasia in the breast: a potentially difficult distinction resolved by cytokeratin 5/6

The solid papillary variant of ductal carcinoma in situ is an uncommon entity, which usually presents in the seventh or eighth decade and may be associated with invasive mucinous carcinoma. Solid papillary ductal carcinoma in situ (SP-DCIS) shares many morphological features with usual ductal hyperplasia (UDH) involving a papilloma: papillary architecture, solid growth, cellular streaming, and low-grade nuclear features. These similarities can make the distinction between these 2 entities challenging. Recent studies have demonstrated that immunohistochemical staining for cytokeratin 5/6 can distinguish UDH from conventional forms of ductal carcinoma in situ. Most of the epithelial cells of UDH express cytokeratin 5/6, but the tumor cells of ductal carcinoma in situ do not. We tested the hypothesis that the results of staining for cytokeratin 5/6 can distinguish UDH from the solid papillary variant of ductal carcinoma in situ. Immunohistochemical staining of 14 cases of SP-DCIS and 9 cases of UDH (4 involving papillomas) was performed using cytokeratin 5/6 antibody clone D5/16 B4. Strong cytoplasmic or membrane staining was considered positive. The hyperplastic cells in all cases of UDH showed strong staining for cytokeratin 5/6. The percentage of positive cells ranged from 50% to 80%. None of the SP-DCIS tumor cells stained for cytokeratin 5/6; however, many cases did show staining of occasional entrapped, benign epithelial, and myoepithelial cells. We conclude that the absence of strong cytokeratin 5/6 expression by SP-DCIS distinguishes it from its morphological mimic, UDH. Pathologists must guard against misinterpreting SP-DCIS as UDH in those cases in which the carcinoma cells engulf cytokeratin 5/6-expressing residual, native epithelial cells.     

Characterization and chemosensitivity of two human malignant peripheral nerve sheath tumour cell lines derived from a patient with neurofibromatosis type 1

 Two new cell lines, designated NMS-2 and NMS-2PC, were established in vitro from a malignant peripheral nerve sheath tumour (MPNST) in the right thigh and a retroperitoneal lesion of a 30-year-old man with neurofibromatosis type 1 (NF1). The NMS-2 cell line was derived from the first tumour, and the NMS-2PC cell line from a retroperitoneal metastatic tumour detected 9 months later. Cultured NMS-2 cells showed epithelioid features, while NMS-2PC cells showed fibroblast-like features. However, both cell lines were strongly positive for S-100 protein. The transplanted NMS-2 and NMS-2PC tumours showed the same histological features typical of MPNST. Chromosomal analysis revealed that only the NMS-2 cells had a t (1;2) chromosomal translocation. Chemosensitivity tests demonstrated that NMS-2PC cells were far more sensitive than NMS-2 cells to Adriamycin and etoposide, which had been used clinically. All-trans-retinoic acid induced a morphological change in NMS-2PC cells so that they were no longer fibroblast-like, but epithelioid cells. We believe the epitheloid components in the MPNST were derived from typical spindle cells. Received: 29 December 1997 / Accepted: 29 June 1998     

Sarcomatoid carcinoma with small cell carcinoma component of the urinary bladder: a case report with review of the literature

Sarcomatoid carcinoma of the urinary bladder is an uncommon neoplasm characterized histopathologically by the presence of malignant spindle cell and epithelial components. Albeit extremely rare, sarcomatoid carcinoma with small cell carcinoma has been reported. Herein, we describe an additional case of sarcomatoid carcinoma with small cell carcinoma and squamous cell carcinoma of the urinary bladder and review the clinicopathological features of this type of tumor. An 82-year-old Japanese male presented with hematuria. Computed tomography demonstrated a large tumor in the urinary bladder. Histopathological study of the resected urinary bladder tumor showed that approximately 80% of the tumor was comprised of small cell carcinoma, and the remaining components were spindle cell proliferation (approximately 15%) and squamous cell carcinoma (5%). Both the spindle cell and squamous cell carcinoma components were intermingled with nests of the small cell carcinoma. This is the fifth documented case of sarcomatoid carcinoma with small cell carcinoma of the urinary bladder. Our review of the clinicopathological features of this type of tumor revealed that: i) elderly males are mainly affected, ii) the most common chief complaint is hematuria, iii) the epithelial component may include urothelial carcinoma, adenocarcinoma, and/or squamous cell carcinoma, and iv) the sarcomatous component is composed of spindle cell proliferation. The histogenesis of this type of tumor remains a matter of controversy. However, recent molecular analyses demonstrated a monoclonal origin of both components. This theory can account for the various types of carcinomatous components in this tumor as seen in the present case.