Infiltrative Margins Research Articles

Pseudomyogenic Hemangioendothelioma

A 1992 report described 5 keratin-positive spindle cell neoplasms with multifocal presentation in a single limb, which were proposed at that time to be a variant of epithelioid sarcoma. This tumor type is not widely recognized and is incompletely characterized. We examined 50 cases of this distinctive tumor to evaluate histologic, immunophenotypic, and clinical features. There was a 4.6:1 male predominance (mean age, 31 y; 82% ≤40 y). Half of the patients presented with painful nodules and the other half with painless nodules. Mean tumor size was 1.9 cm (range, 0.3 to 5.5 cm). Tumors arose in the lower limb (54%), the upper limb (24%), trunk (18%), or head and neck (4%). Thirty-three (66%) were multifocal lesions (ranging from 2 to 15 lesions), including 32 cases with involvement of multiple tissue planes. Of 205 total lesions, 64 (31%) involved the dermis, 42 (20%) involved the subcutis, 70 (34%) lesions involved muscle, and 29 (14%) lesions involved bone; all the lesions had infiltrative margins. The tumors were composed of loose fascicles and sheets of plump spindle cells with vesicular nuclei, variably prominent nucleoli, and abundant brightly eosinophilic cytoplasm, some with a strikingly rhabdomyoblast-like appearance. In all cases, a minority of cells were epithelioid. Twenty-seven tumors contained a prominent neutrophilic inflammatory infiltrate. Most tumors showed only mild nuclear atypia; 6 tumors contained foci of notably pleomorphic cells. The median mitotic rate was 1 per 10 HPF (range, 1 to 10). Seven tumors showed vascular invasion; 7 tumors had areas of necrosis. By immunohistochemistry, all tumors were diffusely positive for AE1/AE3 and FLI1; 22 of 47 tumors were variably positive for CD31. Focal positivity was seen for CAM5.2 (21 of 35), smooth muscle actin (14 of 42), epithelial membrane antigen (7 of 49 weak), and PAN-K (MNF116) (1 of 47). All were negative for CD34, desmin, and S100 protein and showed intact INI1 expression. Follow-up was available for 31 patients and ranged from 9 months to 17 years (mean, 4 y). Most lesions were treated by local excision. Eighteen (58%) patients had local recurrence or developed additional nodules in the same region, all but one, within 1 year of first presentation. Eight patients had postoperative radiation therapy and 6 patients had chemotherapy. Four patients had amputations for multifocal disease. One patient had a regional lymph node metastasis, and, thus far, only 1 patient has developed distant metastases (disseminated), 16 years after primary tumor excision. At the time of the last follow-up, 27 patients were alive with no evidence of the disease, 1 patient was alive with unknown disease status, 2 patients were alive with recurrent disease, and 1 patient died of the disease. In summary, we describe a distinctive type of rarely metastasizing ("intermediate") tumor affecting mainly young men and usually characterized by multifocality in different tissue planes of a limb. Although sharing some features with epithelioid sarcoma (skin/soft tissue of distal extremities, young adults, keratin positive), it differs by having predominantly myoid-appearing spindle cell morphology, expression of FLI1, common reactivity for CD31, lack of epithelial membrane antigen, CD34, and PAN-K expression, and intact INI1. The overall immunophenotypic findings favor endothelial differentiation. Despite the ominous presentation, follow-up thus far suggests an indolent clinical course with a small risk of distant metastasis. Although the precise nosologic status of this tumor type is uncertain, we propose the interim designation "pseudomyogenic hemangioendothelioma."

Impact of radioguided occult lesion localization on the correct excision of malignant breast lesions: effect of histology and tumor size

To evaluate the impact of radioguided occult lesion localization (ROLL) in the correct location and excision of malignant breast lesions, and analyze if these results are affected by the histology and tumor size. A total of 105 patients with occult breast lesions were studied. The mean age was 55 years. An intralesional dose of 18.5 MBq of 99mTc-labeled macroaggregated human albumin (AMA) was administered using stereotaxic mammography or ultrasound. Surgical resection was carried out with the help of a gammadetector probe. In the histological study, disease-free margin was defined by a distance between the tumor lesion and the surgical margin of more than 1 mm. The possible influence of tumor histology and lesion diameter with respect to free/affected margins was analyzed. Correct radiotracer placement was achieved in 100/105 of the cases (95.2%). In the remaining 5 cases (4.8%), radiotracer placement was incorrect, with 2 of them being malignant lesions that were found by macroscopic inspection, and the other 3 having benign pathology. Among the malignant lesions (44 cases), correct placement of the radiotracer was achieved in 42 cases (95.5%). Of these 42 malignant lesions, in which the ROLL was correctly performed, free surgical margins were obtained in 24 cases (57.1%), while the other 18 (42.9%) had infiltrated surgical margins. The most common histological type among the malignant lesions was invasive ductal carcinoma (71.4%). The histological types with an increased frequency of infiltration of surgical margins were invasive and microinvasive cancer (94.4%). All the affected margins were in lesions greater than 10 mm, and the highest incidence was in those between 20 and 30 mm (55.5%). In our experience, the advantages of the ROLL technique are a precise localization of malignant breast lesions (95.5%) and an increased probability of a complete excision with free margins in more than one half of them. Nevertheless, special consideration should be taken when dealing with invasive and microinvasive cancers and in those exceeding 10 mm because of their higher incidence of infiltrated margins.

MRI Features of Renal Oncocytoma and Chromophobe Renal Cell Carcinoma

The purpose of this study was to retrospectively describe the MRI features of the pathologically related entities renal oncocytoma and chromophobe renal cell carcinoma (RCC). Twenty-eight cases of histologically proven renal oncocytoma and 15 of chromophobe RCC evaluated with preoperative MRI from January 2003 through June 2009 at our institution were independently reviewed for an array of MRI features by two radiologists blinded to the final histopathologic diagnosis. These features were tabulated and compared between chromophobe RCC and renal oncocytoma by use of the Mann-Whitney test and binary logistic regression. Renal oncocytoma and chromophobe RCC showed no significant difference in size or any of 16 qualitative imaging features (p = 0.0842-1.0, reader 1; p = 0.0611-1.0, reader 2). Microscopic fat, hemorrhage, cysts, infiltrative margins, perinephric fat invasion, renal vein invasion, enhancement homogeneity, and hypervascularity were each observed in less than 20% of cases by both readers. A central scar and segmental enhancement inversion (a recently described finding in which early contrast-enhanced images show relatively more enhanced and less enhanced intralesional components with inversion of their relative enhancement on later images) were observed by both readers in at least 10% of cases of both renal oncocytoma and of chromophobe RCC with no significant difference between the two entities (p = 0.2092-0.2960). We have presented the largest series to date of the MRI features of both renal oncocytoma and chromophobe RCC. These related entities exhibited similar findings, and no MRI features were reliable in distinguishing between them.

Histological features of medullary carcinoma and prognosis in triple-negative basal-like carcinomas of the breast

Medullary carcinomas have a better prognosis than other grade 3 mammary carcinomas, but they typically show basal-like biological features, which are associated with a poor prognosis. In this study we examined the associations and prognostic relevance of medullary histological features in a series of 165 invasive carcinomas with a basal-like phenotype: triple-negative (oestrogen receptor, progesterone receptor, HER2) and expressing at least one basal marker (CK5/6, CK14, CK17 or EGFR). The following histological features were associated with each other: prominent inflammation, anastomosing sheets, absence of fibrosis, absence of infiltrative margin and absence of gland formation. Prominent inflammation and anastomosing sheets in at least 30% of the tumour were associated with a better prognosis on univariate analysis. The combination of these two features (a simplified definition of medullary-like type) was present in 17% of tumours and was an independent prognostic factor on multivariate analysis. This simplified definition had good inter-observer reproducibility (κ=0.61) and is worthy of more detailed assessment in an unselected group of mammary carcinomas. A fibrotic focus was present in 36% of carcinomas. Only 3% of tumours with a fibrotic focus had features of medullary-like carcinomas. Fibrotic focus of greater than 30% of the tumour was associated with a poor prognosis. This study emphasizes the heterogeneity of morphology and behaviour of triple-negative basal-like carcinomas.

Cystosarcoma phyllodes of the breast: a case report in a 12-year-old girl

Breast tumors in adolescents are very rare and mostly benign. Fibroadenomas are the most frequent, but within the extensive differential diagnosis, the phyllodes tumor must be mentioned, which accounts for about 1% of breast tumors and the diagnosis of which is very rare in patients younger than 20 years. There are no specific symptoms or radiological images to distinguish phyllodes tumor from fibroadenoma; therefore, histological examination is mandatory for diagnosis. Histology also allows the classification of phyllodes tumor into benign, borderline, or malignant types for appropriate surgical treatment: freemargin excision in benign tumors and mastectomy in the other two types. Fortunately, the majority of these tumors are benign, and treatment maximizes breast conservation with free infiltration margins surgery, given that this fact is the most important factor to prevent local recurrence. In this article, we describe a rare case of borderline cystosarcoma phyllodes in a 12-year-old girl.

A successfully treated inflammatory myofibroblastic tumor of the mandible with long-term follow-up and review of the literature

Inflammatory myofibroblastic tumor (IMT) of the oral cavity is an extremely rare clinical and pathological disease entity. It was originally described in the lung but has recently been reported in various anatomic sites. We report such a case of inflammatory myofibroblastic tumor of the mandible in a 14-year-old girl. The patient presented with an aggressive ulcerative soft tissue mass of 3 months duration in the mandibular molar gingiva. Histologically, the lesion was composed of fibroblastic or myofibroblastic spindle cell proliferations with infiltrative margins in an inflammatory background. Immunohistochemically, the fibroblastic or myofibroblastic spindle cells were positive for vimentin, α-smooth muscle actin, and Ki-67 (MIB-1) but negative for desmin, pan-cytokeratin, S-100 protein, CD34, CD68, CD99, bcl-2, β-catenin, estrogen receptor, progesterone receptor, ALK-1, and p53. These spindle cells were focally and weakly Ki-67- (MIB-1-) positive. The MIB-1 labeling index was 5%. The results of in situ hybridization for Epstein-Barr virus-encoded-RNA were negative. The ratio of IgG4+/IgG+ plasma cells was about 10%. A pathological diagnosis of inflammatory myofibroblastic tumor was made. The postoperative course was uneventful, and the patient has had no recurrence in the 10-year follow-up period. Although no evidence of oral inflammatory myofibroblastic tumor recurrence or malignant transformation has been reported, it has been observed that in inflammatory myofibroblastic tumors of other regions, a prolonged follow-up is necessary after surgical resection. No other case of an IMT patient under 20 years of age has appeared in either the English or the Japanese literature.

Pedunculated cutaneous spindle cell/pleomorphic lipoma

Spindle cell/pleomorphic lipoma is an infrequently seen benign adipose tissue tumor. This tumor, mostly arising from the subcutaneous tissue, usually affects male patients and occurs in back, shoulders, head and neck area. It is rarely localized to dermis. Cutaneous spindle cell/pleomorphic lipoma differs from its subcutaneous counterpart by wider anatomical distribution, female predilection and infiltrative margins. We here present a pedunculated type, cutaneous pleomorphic lipoma case localized to the nasolabial region of 59-year-old man.

Which oral cancer patients benefit the most from microsurgical reconstruction?

The objective of this study is to evaluate the impact of microsurgical reconstruction on local recurrence rates and disease-specific survival in patients with oral squamous cell carcinoma. This study is a retrospective review of patients treated at a tertiary cancer center. Six hundred and five patients were included in this study with 529 males (87.44%) and 76 females (12.56%). These were composed of 467 (77.19%) pedicled-flaps reconstructions and 138 (22.81%) free-flap procedures. There was no difference between the groups regarding T stage, N stage, or type of oncological surgery. Use of postoperative radiotherapy was more common in the free-flap group with a significantly shorter time interval than the pedicled-flap group. Free-flap patients had a lower proportion of compromised/close surgical margins (p < 0.0001). Univariate analysis disclosed as significant for local recurrence: gender, T stage, microsurgical reconstruction, lymphatic embolization, neural infiltration, and surgical margins. In a multivariate model, T stage (p < 0.001), neural infiltration (p < 0.001), and microsurgical reconstruction (p < 0.001) remained significant. Significant factors for survival in univariate analysis were: gender, T stage, N stage, synchronous neck dissection, microsurgical reconstruction, lymphatic embolization, neural infiltration, and surgical margins. In a multivariate analysis, T stage (p < 0.001), N stage (p < 0.001), synchronous neck dissection (p = 0.025), microsurgical reconstruction (p < 0.001), lymphatic embolization (p = 0.023), and neural infiltration (p < 0.001) remained significant. Regression trees show a significant impact of free flaps in T3/T4 primary tumors. Use of microsurgical flaps provides a significant improvement in local recurrence and survival in patients with T3–T4a primary tumors. It also reduces the interval between surgery and radiotherapy.

Pathological Findings at Radical Prostatectomy in Japanese Prospective Active Surveillance Cohort

The present study was carried out to analyze pathological features of prostatectomy specimens performed at different timing and trigger during active surveillance. One hundred and thirty-four patients that fit a selection condition similar to the so-called Hopkins' criteria were enrolled into the present study between January 2002 and December 2003. Patients were recommended to start curable treatment when they showed prostate-specific antigen-doubling time of 2 years or shorter or pathological progression at 1-year re-biopsy. Median observation period was 61 months. Fourteen patients underwent radical prostatectomy immediately after enrollment (Group A) whereas 28 patients underwent radical prostatectomy after substantial periods of active surveillance (Group B). Of the 28 Group B, trigger of radical prostatectomy was on protocol in 17 patients (Group B1) whereas 11 patients underwent radical prostatectomy by their preference (Group B2). Upgrade from initial biopsy was observed in 43% of Group A and 68% of Group B. Upgrade was more frequently observed in Group B1 than B2 with border line significance (P = 0.075). Perineural infiltration and positive surgical margin rates of Group B1 were significantly higher than those of B2 (P < 0.05). Unfavorable pathological features of surgical specimens were more frequently observed in patients who underwent radical prostatectomy due to short prostate-specific antigen-doubling time or biopsy findings than those who underwent radical prostatectomy because of other reasons including patients' preference. Rates of unfavorable pathological features at radical prostatectomy that deviate initial selection criteria was high enough to support integration of frequent biopsies into active surveillance program.

Abstract 813: Prognostic impact of the expression of cancer stem cell markers CD166, CD44, EpCAM, ALDH1 and CD133 in colorectal cancer

Abstract Background: The aim of this study was to elucidate the prognostic impact of the putative cancer stem cell (CSC) markers CD166, CD44s, EpCAM, ALDH1 and CD133 by immunohistochemistry in colorectal cancer and determine their value as potential biomarkers of clinical outcome. Methods: Using the tissue microarray technique, immunohistochemistry was performed on samples from 1420 primary colorectal cancer patients with full clinico-pathological data and 57 normal tissues. Expression was evaluated semi-quantitatively and receiver operating characteristics (ROC) curve analysis was used to identify reliable cut-off scores for positivity. Prognostic effects were subsequently validated using 101 randomly selected whole tissue sections. Invasive potential was tested using 3 colorectal cancer cell lines. Surgically excised colorectal cancer specimens were enzymatically digested and expression of CD166, CD44s and CD133 on tunour cells was evaluated by flow-cytometry. Cells were then injected in limiting amounts s.c. in NOD/SCID mice and allograft outgrowth was monitored by standard methods. Results: A significant increase in CD166, CD44s and CD133 expression and a decreased expression of EpCAM and ALDH1 was noted in tumour compared to normal mucosa (p&amp;lt;0.001, all markers). Loss of membranous CD166, CD44s and EpCAM expression was associated with features of tumour progression, in particular with an infiltrating tumour border configuration (CD166: p&amp;lt;0.001; CD44s: p=0.002; EpCAM:p=0.005). Loss of CD166 and CD44s had a significant negative impact on survival time (p&amp;lt;0.001), which was further confirmed by evaluating corresponding whole tissue sections (p=0.006). CD44-/CD166- cells from 3 colorectal cancer cell lines exhibited in vitro significantly higher invasive potential than their positive counterparts. On the other hand, the ability of cancer cells to initiate tumours in immunodeficient mice was significantly (p=0.03) correlated with their content in CD133+, but not in CD166+/CD44+ cells. Conclusions: Our findings indicate that loss of expression of CD166 and CD44s is linked to an aggressive tumour phenotype and, particularly, to the presence of an infiltrating tumour margin, possibly implicating these proteins in events at the invasive tumour front. Remarkably, the number of CD133+ cells, while important for tumour initiation in immunodeficient hosts, appears to be prognostically irrelevant in possibly immunocompetent patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 813.

Prognostic factors affecting survival and recurrence after hepatic resection for hepatocellular carcinoma in cirrhotic liver

Hepatic resections for hepatocellular carcinoma (HCC) in cirrhotic liver are characterized by early recurrence and poor survival. In this study, we analyzed several factors affecting both survival and recurrence after hepatic resection. From October 1995 to April 2007, 550 patients underwent hepatic resections, of which, 175 patients had HCC in cirrhotic liver in Gastroenterology Surgical Center, Mansoura University, Egypt. There were 131 males (74.9%) and 44 females (25.1%) with a mean age of 54.8 +/- 9.2 years (ranges from 26 to 75 years). Most of our patients were in Child's Pugh class A (86.9%). Major hepatic resection was done for 65 patients (37.1%), segmentectomy was done for 62 patients (35.4%), and localized resection was done for 48 patients (27.4%). Hospital mortality occurred in 16 (9.1%) patients, while hospital morbidity occurred in 40% of patients. The 1, 3, and 5 years survival were 68.6%, 29.6%, and 10.7%, respectively. The prognostic factors affecting recurrence were multifactorial, and the univariate analysis showed that multifocality of the tumor (p = 0.006), capsule (p = 0.001), staging (p = 0.001), blood transfusion (p = 0.02), infiltration of the cut margin (p = 0.001), vascular invasion (p = 0.006), and lymph nodes infiltration (p = 0.014) affect the recurrence rate, while with multivariate analysis, only cut margin was significantly affecting the recurrence (p = 0.026). Also, factors that significantly predicted survival were preoperative serum albumin (p = 0.005), tumor differentiation (p = 0.008), staging (p = 0.001), tumor's capsule (p = 0.001), cut margin (p = 0.031), vascular invasion (p = 0.049), and operative blood transfusion (p = 0.001). However, tumor differentiation (p = 0.048) was the only independent factor on multivariate analysis affecting long-term survival. In our experience, the prognostic factors after resection for recurrence and survival are different and multifactorial. However, resection of HCC in cirrhotic liver with preserved liver function is the treatment of choice in the present time and can be done with favorable results.

Miniaturized Handheld Confocal Microscopy for Neurosurgery

Recent developments in optical science and image processing have miniaturized the components required for confocal microscopy. Clinical confocal imaging applications have emerged, including assessment of colonic mucosal dysplasia during colonoscopy. We present our initial experience with handheld, miniaturized confocal imaging in a murine brain tumor model. Twelve C57/BL6 mice were implanted intracranially with 10(5) GL261 glioblastoma cells. The brains of 6 anesthetized mice each at 14 and 21 days after implantation were exposed surgically, and the brain surface was imaged using a handheld confocal probe affixed to a stereotactic frame. The probe was moved systematically over regions of normal and tumor-containing tissue. Intravenous fluorescein and topical acriflavine contrast agents were used. Biopsies were obtained at each imaging site beneath the probe and assessed histologically. Mice were killed after imaging. Handheld confocal imaging produced exquisite images, well-correlated with corresponding histologic sections, of cellular shape and tissue architecture in murine brain infiltrated by glial neoplasm. Reproducible patterns of cortical vasculature, as well as normal gray and white matter, were identified. Imaging effectively distinguished between tumor and nontumor tissue, including infiltrative tumor margins. Margins were easily identified by observers without prior neuropathology training after minimum experience with the technology. Miniaturized handheld confocal imaging may assist neurosurgeons in detecting infiltrative brain tumor margins during surgery. It may help to avoid sampling error during biopsy of heterogeneous glial neoplasms, with the potential to supplement conventional intraoperative frozen section pathology. Clinical trials are warranted on the basis of these promising initial results.

Low expression of chemokine receptor CCR5 in human colorectal cancer correlates with lymphatic dissemination and reduced CD8+ T-cell infiltration

Chemokines and their receptors have been proposed to distinctly contribute to tumor growth, dissemination, and local immune escape. The aim of this study was to evaluate the relevance of the chemokine receptor CCR5 expression for the progression of human colorectal cancer. CCR5 expression was assessed by RT-PCR analysis in 103 colorectal cancer patients. Intensity of CCR5 expression was correlated with both tumor and patient characteristics. Infiltration of tumor margins with CD8(+) T cells in the context of CCR5 expression was analyzed by immunohistochemistry in additional 18 colorectal cancer specimens. Human colorectal cancer revealed variable intensities of CCR5 expression ranging from absent (48/103: 47%), weak (30/103: 29%), intermediate (13/103: 13%), to strong (12/103: 12%). Absent or weak CCR5 expression was significantly associated with advanced UICC stages (P=0.02) and lymphatic metastasis (P=0.05). In addition, CCR5 expression positively correlated with CD8(+) T-cell infiltration in tumor margins (P=0.001). In summary, intermediate and strong CCR5 expression was significantly associated with nonmetastatic colorectal cancer and increased CD8(+) T-cell infiltration.

Infiltrating glomus tumor of uncertain malignant potential arising in the kidney

Glomus tumors closely resemble the normal glomus body and have a predilection for skin and subcutaneous tissue. These tumors rarely present in visceral organs. We report a case involving the kidney. This glomus tumor displays typical cytology and immunohistochemical profile of glomus tumors elsewhere. However, this tumor is large, has a deep location and exhibits an infiltrative margin and increased mitotic activity. These features, by current definition, would suggest malignant behavior. However, the rarity of such an entity in the kidney highlights the need for caution and a diagnosis in a continuum between benignity and malignancy. To the best of our knowledge, this report is the first case of infiltrating glomus tumor or glomus tumor of uncertain malignant potential arising in the kidney.

Systematic assessment of the prognostic impact of membranous CD44v6 protein expression in colorectal cancer

To assess systematically the membranous expression of CD44v6 in colorectal cancer by immunohistochemistry to determine its prognostic impact, the differential expression between primary and metastatic tumours and expression differences between the tumour centre and invasive front. Immunohistochemistry was performed for CD44v6 on two tissue microarrays. The first included 1279 colorectal tumours with full clinicopathological data. The second consisted of 50 matched primary and metastatic tumours sampled from the tumour centre and the invasive margin. A scoring system was tested by multiple observers. Receiver-operating characteristic curve analysis was used for cut-off point determination. Loss of membranous CD44v6 was associated with pT stage (P = 0.016; sensitivity 85.8%, specificity 20.1%), lymph node metastasis (P = 0.015; sensitivity 52.8%, specificity 55%), an infiltrating tumour margin (P < 0.001; sensitivity 71.4%, specificity 40%) and adverse prognosis (P = 0.011; hazard ratio 0.79, 95% confidence interval 0.7, 0.9), but was not an independent prognostic factor on multivariable analysis. Loss of expression occurred at the invasive front in both primary and metastatic lesions (P < 0.001). This study outlines an approach to help standardize the immunohistochemical evaluation of CD44v6 and similar markers in colorectal cancer and highlights a significant role for loss of membranous CD44v6 expression in colorectal cancer progression and prognosis.

Cancer Of The Penis: Case Report

Two patients with penile carcinoma are presented after management at a district hospital in Kenya. Both had undergone ritual circumcision as teenagers and presented late. HR was a 73 year old who presented with a fungating penile mass for which a partial penectomy was performed after wedge biopsy confirmed malignancy. He thereafter declined to have the surgical specimen sent for histology and took the amputated stump for burial in his compound to avoid bad omen. GK was 25 years old and presented with a fungating mass and underwent partial penectomy after a histological diagnosis was made. He absconded from follow-up after being informed of the need for further surgery due to tumour infiltration of the surgical margins. The history and clinical images are presented and we discuss the difficulties of cancer management at a rural district hospital.

Hybrid Schwannoma/Perineurioma

Benign nerve sheath tumors include neurofibromas, schwannomas, and perineuriomas. In recent years, nerve sheath tumors showing discrete areas of more than one histologic type have been described. We have recently recognized tumors showing hybrid features of schwannoma and soft tissue perineurioma. To characterize the clinicopathologic and immunohistochemical features of these lesions, 42 cases received between 1994 and 2008 were retrieved from authors' consult and surgical pathology files. Clinical details and follow-up were obtained from referring pathologists. Hematoxylin and eosin-stained sections were reexamined, and immunohistochemistry was performed. On 10 cases, double labeling with epithelial membrane antigen (EMA) and S100 protein was performed. Twenty-two patients were female and 20 were male (mean age, 38 y; range: 2 to 85; 71% second to fifth decades). Most patients presented with a solitary painless nodule. The tumors arose in a wide distribution: 19 lower limb, 12 upper limb, 6 head and neck, 4 trunk, and 1 colon. None of the patients showed signs of neurofibromatosis. Tumor size ranged from 0.7 to 17.5 cm (mean, 3 cm). Most tumors involved superficial subcutis (11 also dermis); only 3 were intramuscular. Histologically, the tumors were usually well circumscribed but unencapsulated, and composed of spindle cells with plump, tapering nuclei, and palely eosinophilic cytoplasm with indistinct cell borders, arranged in a storiform, whorled, and/or lamellar architecture. Only 1 tumor showed infiltrative margins. One tumor showed a plexiform growth pattern. Antoni A and B zonation and hyaline vessels were absent. Six tumors showed focally myxoid stroma and 11 contained scattered cells with degenerative nuclear atypia. Mitoses ranged from 0 to 4 per 30 high power fields; 32 tumors had no mitoses. All tumors showed staining for S100 protein and EMA; 98% were positive for CD34, 84% for GFAP, and 80% for claudin-1. Fourteen tumors contained rare neurofilament protein-positive axons. Double staining for EMA and S100 protein revealed parallel layers of alternating S100 and EMA-positive cells with no coexpression of antigens by the same cells. Most tumors were composed of approximately 60% to 70% of Schwann cells and 30% to 40% of perineurial cells. After a mean follow-up of 24 months (range, 6 to 60 mo), 1 tumor recurred locally, after incomplete excision. Benign nerve sheath tumors showing predominantly schwannian cytomorphology and perineurioma-like architecture are composed of an admixture of both cell types. These tumors usually arise in the dermis and subcutis and occur over a wide age range and anatomic distribution. Degenerative nuclear atypia (akin to that seen in ancient schwannoma and atypical neurofibroma) is relatively common. Hybrid schwannoma/perineuriomas have no evident association with neurofibromatosis and rarely recur. The pathogenetic basis of the dual pattern of differentiation in these lesions remains poorly understood at this time.

Urokinase-type plasminogen activator is a marker of aggressive phenotype and an independent prognostic factor in mismatch repair-proficient colorectal cancer

The aim of this study was to determine the prognostic significance of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in colorectal cancer stratified by mismatch repair status and to determine their contribution to the aggressive phenotype predicted by loss of E-cadherin and apoptosis protease activating factor-1 (APAF-1). Immunohistochemistry for uPA and uPAR was performed on a tissue microarray comprising 811 mismatch repair-proficient and 164 mismatch repair-deficient colorectal cancers. Immunoreactivity was scored semiquantitatively and the interobserver agreement between multiple pathologists was determined. Optimal cutoff scores for uPA and uPAR positivity were obtained by receiver operating characteristic curve analysis. Agreement between pathologists was excellent for uPA and uPAR. Cutoff scores of 60% for uPA and 75% for uPAR were validated by resampling of the data. In mismatch repair-proficient colorectal cancer, overexpression of uPA and uPAR was associated with advanced pT stage (P = .009, both), an infiltrating margin (P = .009 and P = .033, respectively), and poor prognosis (P = .002 and P < .001, respectively). uPA, but not uPAR, maintained its significant prognostic effect in multivariable analysis (P = .037). In addition to loss of APAF-1 (P = .002) and E-cadherin (P < .001), uPA independently predicted an infiltrating margin (P = .016). Our findings suggest that uPA, but not uPAR, is an independent prognostic factor and that this negative effect on survival is relevant specifically for mismatch repair-proficient colorectal cancers. Moreover, the combination of uPA with E-cadherin and APAF-1 is linked to an aggressive tumor phenotype and highly predictive of an infiltrating growth pattern.

Feline injection-site sarcoma: Recurrence, tumour grading and surgical margin status evaluated using the three-dimensional histological technique

The three-dimensional histology technique is used in human medicine for the evaluation of complete lateral and deep surgical margins. In this study, the technique was applied to 48 excised feline injection-site sarcoma specimens. The predictive value of the histological margin status and tumour grading on local recurrence was investigated. In 32/48 cases, the margins were non-infiltrated, whilst in the remaining 16 cases, they were infiltrated. Overall, 6/32 (19%) tumours with non-infiltrated margins and 11/16 (69%) with infiltrated margins recurred. Tumours with infiltrated margins recurred about 10 times more frequently compared to tumours with non-infiltrated margins (P=0.0011). No statistically significant correlation was observed between grading and recurrence. The assessment of margin status using the 3D histology technique showed a good predictivity for post-surgical tumour recurrence. Extensive application of the 3D histology technique is recommended to standardise the evaluation of histological margins and to allow comparison between results from different laboratories.

Fibromatosis mamaria, diagnóstico diferencial del carcinoma invasor: Reporte de un caso

Breast fibromatosis. Report of one case Desmoid tumors or fibromatosis, a rare lesion of the connective tissue, corresponds to 0.2% of breast tumors. It does not metastasize but has high local recurrence rates due to margin infiltration. The clinical presentation and imaging is almost indistinguishable from breast carcinoma. Diagnosis is histological and the treatment of choice is surgical excision. We report a 31 years old woman consulting for skin retraction in right breast, without previous history of trauma or surgery. Breast ultrasound showed an irregular nodule that extended into the skin. The mammogram showed a discrete retraction of the skin and increased density of adjacent subcutaneous tissue. An ultrasound guided percutaneous biopsy showed stromal fusocelular proliferation, suggesting a phyllodes tumor. A partial mastectomy was performed and the pathological study of the surgical piece showed a mesenchymal proliferation with infiltrative borders, consistent with breast fibromatosis.