High grade phyllodes tumor with osteosarcomatous differentiation: Case report and review of the literature.

Phyllodes tumors (PTs) are rare fibroepithelial malignancies of the breast, accounting for less than 1% of malignant breast tumors. PTs are usually solitary tumors but can be associated with other malignancies, such as DCIS or invasive carcinomas and sarcomas. Osteosarcomatous differentiation of a malignant phyllodes tumor is rare, and differentiation of this rare breast tumor from other entities is of vital importance to clinicians due for appropriate treatment and prognosis. We present a case of rare high-grade phyllodes tumor with osteosarcomatous differentiation presenting on mammogram as a calcified lobulated mass; ultrasound revealed a 1.5 cm irregularly calcified mass, suggestive of bone. An ultrasound-guided core biopsy and subsequent lumpectomy revealed a cellular stroma with osteoid stromal matrix and cytologic atypia with bone formation. At 18 months postprocedure, a recurrence was identified at the previous surgical site, and the patient underwent a mastectomy. Here we present a single case of high-grade PT with osteosarcomatous differentiation and a comprehensive literature review, highlighting the mammographic and histologic characteristics of this rare presentation.

Role of SIRT1 and Progesterone Resistance in Normal and Abnormal Endometrium.

CONTEXT: Progesterone resistance, a known pathologic condition associated with a reduced cellular response to progesterone and heightened estrogen responses, appears to have a normal physiologic role in mammalian reproduction. The molecular mechanism responsible for progesterone resistance in normal and abnormal endometrium remains unclear. OBJECTIVE: To examine the roles of sirtuin-1 (SIRT1) in normal endometrium as well as endometrium associated with infertility and endometriosis, as an epigenetic modulator associated with progesterone resistance. METHODS: SIRT1 expression was examined by Western blot, quantitative real-time polymerase chain reaction, and immunohistochemistry in mouse uterus and human endometrium. Mice with uterine specific Sirt1 overexpression were developed to examine SIRT1's role in endometrial function and endometriosis development. EX-527, a SIRT1 inhibitor, and SRT1720, a SIRT1 agonist, were also used to evaluate SIRT1 effect on endometriosis. RESULTS: In normal healthy women, endometrial SIRT1 is expressed only during menses. SIRT1 was dramatically overexpressed in the endometrium from women with endometriosis in both the epithelium and stroma. In mice, SIRT1 is expressed at the time of implantation between day 4.5 and 5.5 of pregnancy. Overexpression of SIRT1 in the mouse uterus leads to subfertility due to implantation failure, decidualization defects and progesterone resistance. SIRT1 overexpression in endometriotic lesions promotes worsening endometriosis development. EX-527 significantly reduced the number of endometriotic lesions in the mouse endometriosis model. CONCLUSIONS: SIRT1 expression and progesterone resistance appears to play roles in normal endometrial functions. Aberrant SIRT1 expression contributes to progesterone resistance and may participate in the pathophysiology of endometriosis. SIRT1 is a novel and targetable protein for the diagnosis as well as treatment of endometriosis and the associated infertility seen in this disease.

Evaluation of BCL6 and SIRT1 as Non-Invasive Diagnostic Markers of Endometriosis.

(1) Background: Endometriosis is characterized by the presence of endometrial glands and stroma outside of the uterus and is often associated with severe pelvic pain and infertility. Our study explored the utilization of B-Cell Lymphoma 6 (BCL6) and Sirtuin 1 (SIRT1) as potential biomarkers in serum, plasma, urine, and cervical mucus for a non-invasive diagnostic test for endometriosis. BCL6 was chosen based on its previously reported elevated expression in endometrial biopsies, and SIRT1 is co-expressed and upregulated in the endometrium of women with endometriosis. (2) Methods: BCL6 and SIRT1 levels were measured using enzyme-linked immunoassay (ELISA) in samples from 20 women with endometriosis (ten with stages I/II and ten with stages III/IV) and ten women without endometriosis. (3) Results: Levels of SIRT1 in sera showed a statistically significant elevation in advanced stages III/IV compared to controls and stages I/II. No significant differences were found in other bodily fluids for SIRT1 or any bodily fluids tested for BCL6. (4) Conclusions: These results suggest some potential of SIRT1 expression within serum as a predictor of advanced asymptomatic stages of endometriosis. Using immunohistochemistry (IHC) staining and H-SCORE values for the elevated BCL6 (and potentially SIRT1) levels in endometrial biopsy samples seems to have higher diagnostic potential based on the previously published studies.

Differential Expression of KRAS and SIRT1 in Ovarian Cancers with and Without Endometriosis.

Accumulating research shows that ovarian cancer progression can be influenced by both gene mutations and endometriosis. However, the exact mechanism at hand is poorly understood. In the current study, we explored the expression of KRAS and SIRT1, two genes previously identified as altered in endometriosis and ovarian cancer. Human endometrial samples were obtained from regularly cycling women with endometriosis, ovarian cancer, and endometriosis-associated ovarian cancer between 18 and 50 of age undergoing hysterectomy, and immunohistochemical analyses were performed. The cytoplasmic expression of KRAS was low in eutopic endometrium from women without endometriosis or ovarian cancer; however, it was elevated in those who have been diagnosed with endometriosis, as well as ovarian cancer with or without the presence of endometriosis. Nuclear and cytoplasmic SIRT1 expression was also low within endometrium without either disease. However, nuclear SIRT1 expression was increased in those with endometriosis and ovarian cancer associated with endometriosis. Nuclear but not the cytoplasmic expression of SIRT1 correlated with KRAS expression in ovarian cancers associated with endometriosis. These results suggest roles of KRAS and SIRT1 in endometriosis and endometriosis-associated ovarian cancer. Cytoplasmic KRAS expression proves to be a key biomarker in both diseases, while nuclear SIRT1 may be a new biomarker specific to those with endometriosis and those with both endometriosis and ovarian cancer. Further research of these genes could aid in determining the pathogenesis of both diseases and help in clarifying the development of endometriosis-associated ovarian cancer.

Unexplained recurrent pregnancy loss and unexplained infertility: twins in disguise.

STUDY QUESTION: Is B-cell CLL/lymphoma 6 (BCL6) endometrial expression, a surrogate biomarker of endometriosis, elevated in women with unexplained recurrent pregnancy loss (uRPL) and unexplained infertility (UI) compared to fertile subjects? SUMMARY ANSWER: Endometrial BCL6 expression is elevated to a similar degree in women with uRPL and UI compared to fertile controls. WHAT IS KNOWN ALREADY: Endometriosis has been linked to the genesis of endometrial progesterone resistance and to specific nuclear proteins, including endometrial BCL6. BCL6 overexpression (immune histologic score > 1.4) has been strongly associated with poor reproductive outcomes in IVF cycles in women with UI. Our previous data have demonstrated an accuracy of 94% for diagnosing endometriosis, and BCL6 protein is elevated in the decidua of women with uRPL. STUDY DESIGN SIZE DURATION: In this case-control study, at a tertiary university teaching hospital, 110 samples (control n = 28; uRPL n = 29; UI n = 53) from pathological archives were analyzed. Timed endometrial biopsies were obtained between 2 January 2002 and 31 December 2016. PARTICIPANTS/MATERIALS SETTING METHOD: LH-timed endometrial biopsies were obtained from women with UI, uRPL (two or more consecutive losses) and normal fertile subjects during the mid-secretory phase of the menstrual cycle. Endometrial BCL6 protein levels were compared in women with UI and uRPL and fertile controls using western blot analysis and immunohistochemistry (HSCORE). MAIN RESULTS AND THE ROLE OF CHANCE: The mean age of the uRPL group was significantly higher than the others [mean (SD)] control = 32.7 (2.6); uRPL = 35.8 (3.7); UI = 32.7 (4.4); P = 0.002, ANOVA]. Seventy-nine percent of women in both subfertile groups (uRPL and UI, 65 out of 82) displayed elevated BCL6 protein levels. From these, a subset of cases with abnormal BCL6 went to laparoscopy and endometriosis was found in 9 out of 11 cases of uRPL and in 20 out of 21 cases of UI. Median BCL6 HSCORE for controls versus uRPL and UI was significantly different [median (interquartile); control = 0.3 (0.02 to 0.5); uRPL = 3 (1.9 to 3.6); UI = 2.9 (1.6 to 3.1); P < 0.0001, Kruskal-Wallis]. A significant trend in the association between the degree of infertility (fertile, uRPL and UI) and the HSCORE level (negative, medium and high) was found (P < 0.001; x 2 for trend). Western blot of representative samples from each group demonstrated similar findings based on protein levels in the whole endometrium. After running ANCOVA analysis for age difference, the BCL6 difference among groups was still significant (P-value < 0.0001). LIMITATIONS REASONS FOR CAUTION: We studied subjects with two consecutive pregnancy losses rather than the definition adopted in Europe of three losses. The findings may lack external validity in other clinical settings (e.g. low prevalence of endometriosis). WIDER IMPLICATIONS OF THE FINDINGS: Based on the data presented here, we postulate that the degree of BCL6 expression may represent a continuum of progesterone resistance and response to inflammation that occurs in women with endometriosis, yielding different degrees of infertility, from uRPL to UI. STUDY FUNDING/COMPETING INTERESTS: This study was supported by NICHD/NIH R01 HD067721 (SLY and BAL), by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior: Grant 99999.003035/2015-08 (BAL) and by CAPES/PROAP (RFS). Two authors (BAL, SLY) have licensed intellectual property for the detection of endometriosis. Dr Bruce Lessey is an unpaid scientific Advisor for CiceroDx. The other authors report no conflict of interest.

GIST identified during bariatric surgery: to treat or not to treat?

BACKGROUND: Gastrointestinal stromal tumors (GIST) are rare GI tumors that compose 1% of GI tumors. With the rise in obesity, bariatric surgery is becoming an increasingly common procedure and the incidental GISTs in this population have been noted more often than in the general population. OBJECTIVE: We evaluated and characterized the incidental GISTs in our bariatric surgical population. SETTING: The study was completed at a Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program-accredited academic hospital system. METHODS: All GISTs identified during Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy between January 1, 2005 and December 31, 2016 were evaluated. Typical demographic, clinicopathologic, treatment, follow-up, and outcome data were recorded. RESULTS: Within the 2655 bariatric surgeries at our institution, 17 GISTs were identified (.64%). Mean age was 54 years; 94% of lesions were identified intraoperatively. Lesions were identified in the fundus (29.4%) or body (70.6%), were unifocal, and <1 cm; 94.1% of resections had clear margins. Histology revealed 88.2% spindle cell and 11.8% mixed histology with <5 mitoses/50 fields, portending a low malignancy potential. Follow-up included the bariatric surgeon and oncology consult; 17.6% were recommended by oncology for computed tomography surveillance. No recurrences were recorded. CONCLUSION: We present the largest cohort to date of incidental GISTs in a bariatric population. A diligent intraoperative examination of the serosa in the left-behind portion of the remnant in bypass and the discarded remnant in sleeves allows the bariatric surgeon the opportunity to leave the patient cancer-free after removal of incidental tumor.

Primary undifferentiated sarcoma of the meninges: A case report and comprehensive review of the literature.

BACKGROUND AND IMPORTANCE: Sarcomas make up 1% of all cases of adult cancer, with 5-10% of those classified as undifferentiated pleomorphic sarcomas (UPS/PUS) and 0.1-4.3% primary intracranial sarcomas. Intracranial undifferentiated sarcoma is characterized by an earlier age of onset and generally poorer prognosis compared to extracranial undifferentiated sarcomas. Current therapies involve surgical excision with wide margins and radiotherapy, with minimal data available regarding the efficacy of chemotherapy. CASE DESCRIPTION: A 79-year-old man with a history of remote superficial bladder cancer presented with a large frontal scalp lesion. A biopsy was initially attempted by a dermatologist in the outpatient setting, but a follow-up CT scan revealed a skull-eroding, enhancing soft tissue lesion. Neurosurgical treatment revealed an undifferentiated sarcoma. The patient underwent adjuvant radiation therapy of 59.4 Gy fractionated over 45 days following surgery. Follow-up brain MRIs at 1-, 6-, 9-, 12-, 15-, 21-, and 27 months after surgery have not shown any indications of local recurrence or tumor metastasis. Despite the high propensity that undifferentiated sarcomas have for recurrence and metastasis and the patient's advanced age, this patient remains uniquely disease-free. CONCLUSION: We provide a description of an unusual case and comprehensive literature review of UPS to clarify the hallmarks of the disease, identify the difficulties in diagnosis, and provide a summary of therapies employed in the literature with their corresponding patient outcomes.

Mutational analysis of selected high-grade malignancies in a premenopausal gynecologic cancer population: a potential for targeted therapies?

Background: In 2017, there will be 107,000 cases of gynecologic cancer diagnosed in the US with an overall survival of around 70%-most occurring in post-menopausal individuals. In this study, we have examined a younger (≤ 40 years of age) subpopulation of these women with high grade/ high stage gynecologic malignancies, attempting to identify unique genetic abnormalities or combinations thereof through tissue block specimens. This information was then analyzed in light of known target therapies to see if genetic analysis in this setting would yield significant therapeutic advantage. Methods: We retrospectively evaluated patients with high grade/high stage gynecologic cancers (≤ 40 years of age), examined the presence and status of 400 oncogenes and tumors suppressor genes from Formalin-fixed, Paraffin-embedded (FFPE) tissue and functionally classified mutations by SIFT and Polyphen. Results: Twenty women were identified and stratified into positive and negative outcomes. No demographic, clinicopathologic or treatment factors were significant between these groups. Of the 400 genes evaluated, twelve mutations were significant between the groups, six with targeted therapies. Mutations associated with negative outcomes within histologies/locations were evaluated: ERBB3 in epithelial (ovarian), ALK/GPR124/KMT2D in neuroendocrine (ovarian/endometrial), ROS1/EGFR, ROS1/ERBB3/KMT2D/NIRK1 and GPR124 in sarcoma. All negative outcomes were void of mutations in APC/ABL2. A predictive model for negative outcomes in our cohort was developed from these data: AKAP9-/MBD1-/APC-/ABL2- with a mutation load of > 20.5. Conclusions: Unique multi-gene and mutational outcome correlations were identified in our cohort. Resulting complex mutational profiles in distinctly aggressive gynecologic cancers suggested potential for novel therapeutic treatment. Future larger scale studies will be needed to correlate the genotypic and phenotypic features identified here (AU)

KRAS Activation and over-expression of SIRT1/BCL6 Contributes to the Pathogenesis of Endometriosis and Progesterone Resistance.

Endometriosis is an inflammatory condition that is associated with progesterone resistance and cell proliferation, resulting in pain, infertility and pregnancy loss. We previously demonstrated phosphorylation of STAT3 in eutopic endometrium of infertile women with this disorder leading to over-expression of the oncogene BCL6 and stabilization of hypoxia-induced factor 1 alpha (HIF-1α). Here we report coordinated activation of KRAS and over-expression of Sirtuin 1 (SIRT1), a histone deacetylase and gene silencer, in the eutopic endometrium from women with endometriosis throughout the menstrual cycle. The mice with conditional activation of KRAS in the PGR positive cells reveal an increase of SIRT1 expression in the endometrium compared to control mice. The expression of progesterone receptor target genes including the Indian Hedgehog pathway genes are significantly down-regulated in the mutant mice. SIRT1 co-localizes with BCL6 in the nuclei of affected individuals and both proteins bind to and suppress the promoter of GLI1, a critical mediator of progesterone action in the Indian Hedgehog pathway, by ChIP analysis. In eutopic endometrium, GLI1 expression is reduced in women with endometriosis. Together, these data suggest that KRAS, SIRT1 and BCL6 are coordinately over-expressed in eutopic endometrium of women with endometriosis and likely participate in the pathogenesis of endometriosis.

The impact of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial: An institutional review.

BACKGROUND: Axillary dissection (AD) was historically recommended for all patients with breast tumor involvement discovered by sentinel lymph node biopsy (+SLNB). However, after the ACOSOG Z0011 trial, omission of AD became the recommendation for selected patients with a +SLNB. We report the impact of ACOSOG Z0011 on the completion AD rate in patients with +SLNB at our institution. METHODS: We retrospectively reviewed all patients diagnosed with breast cancer between March 2009 and February 2013 (n = 1781). This cohort was divided into two groups: 1) those diagnosed BEFORE Z0011 and 2) those diagnosed AFTER Z0011. We calculated both the percentage of patients with a +SNLB who underwent AD and, from those patients, the percentage who did and did not meet the Z0011 criteria. RESULTS: The BEFORE group contained 849 patients; 144 had +SLNB and from those 113 underwent AD. The AFTER group contained 932 patients: 139 had +SLNB and from those 73 underwent AD. The completion AD rate in the BEFORE group was 78.5%, compared to 52.5% in the AFTER group (p < 0.001). From the patients who met the Z0011 criteria, 75.6% of the BEFORE patients underwent AD, compared to only 2.2%% in the AFTER group (p < 0.001). Among those who did not meet the Z0011 criteria, a similar percentage of patients underwent AD in each group (BEFORE 79.8%, AFTER 74.4%, p = 0.384). CONCLUSION: Following the publication of the ACOSOG Z0011 trial, we experienced a significant decrease in the completion AD rate among patients with a +SLNB who met the Z0011 inclusion criteria.

Endometrial BCL6 Overexpression in Eutopic Endometrium of Women With Endometriosis.

The objective of this study was to examine B-cell CLL/lymphoma 6 (BCL6) expression in human eutopic endometrium across the menstrual cycle in women with and without endometriosis and to establish a cutoff for future studies. This design was a series of case-control studies in tertiary University teaching hospitals. We examined BCL6 expression by messenger RNA and immunohistochemically in prospectively collected samples in both the proliferative (P) and the secretory phases. BCL6 is minimally increased in the mid-secretory phase of the menstrual cycle compared to the P phase in normal patients. BCL6 protein expression was significantly higher in the secretory phase of patients with endometriosis (n = 29) versus fertile controls without endometriosis at laparoscopy (n = 20; P < .0001). Normal fertile controls (n = 28) recruited for endometrial biopsy also had low levels of secretory phase BCL6 expression compared to women with unexplained infertility (UI; n = 119). A receiving-operator characteristic analysis of these data revealed an area under the curve of 94% (95% confidence interval 85%-100%; P < .0001) with an HSCORE cutoff of 1.4 to differentiate cases with and without endometriosis. Using this cutoff value, BCL6 was positive in 88% of cases with UI. Laparoscopic examination of a subset of 65 patients confirmed abnormalities in 98% of cases; 61 (93.8%) were found to have endometriosis, 3 (4.6%) with hydrosalpinx, and 1 (1.5%) with a normal pelvis. These data suggest that BCL6 is a promising candidate as a single diagnostic biomarker for detection of endometriosis in women with otherwise UI and may be associated with endometrial dysfunction, including progesterone resistance.

Management of periampullary adenocarcinoma by pancreaticoduodenectomy at a regional teaching hospital.

BACKGROUND: Periampullary adenocarcinoma (PA) includes: pancreatic, duodenal and ampullary adenocarcinoma; and cholangiocarcinoma. Pancreaticoduodenectomy (PD) is required for cure of PA. Previous studies demonstrated the likelihood of cure increases when a microscopically negative (R0) margin is achieved. Clearance of the superior mesenteric artery (SMA) margin has been identified as the most critical margin in PD. Some authors have emphasized the importance of certain techniques to clear the SMA margin. Neither the degree to which these techniques have been incorporated nor their impact on margin status and survival has been described. We hypothesized that use of techniques focusing on clearing the SMA margin would result in higher R0 resection rates and improved survival after PD in patients with PA. METHODS: A retrospective study was performed on patients from 1/1/1985 until 7/31/2007. Data on patient demographics, clinical presentation, preoperative treatment, operative technique, margins, and postoperative outcomes were collected. Ninety-three patients were identified for inclusion in the study. Three approximately equal groups were created for analysis. RESULTS: The overall survival (OS) for the entire cohort was 19 months and was not different among the groups studied. Margins were microscopically negative in 81% of cases. The percentage of node-positive cases increased during the time period, as did the number of lymph nodes (LNs) examined (P=0.017). The use of pylorus-preserving PD decreased (P=0.001) while resection of the superior mesenteric/portal vein (SMV/PV) increased during the study period. We observed an increase in descriptions of the clearance of the anterior aspect of the aorta and inferior vena cava (IVC), dissection to the right side of the SMA, dissection to the origin of the SMA and intra-operative identification of the SMA margin. Dissecting to the SMA did not change the likelihood of achieving an R0 margin. OS was improved after R0 resections (R0: 21 months vs. R1/2: 10 months) but this difference was not statistically significant (P=0.099). There was no association between margin status and OS. Changes in the pathology reporting of margins were observed, with statistically significant increases in the percentage of cases in which the SMA, common bile duct and pancreatic neck margins were separately reported. However, the SMA margin was separately reported in only 26% of pathology reports. CONCLUSIONS: The operative techniques used in PD at this institution have changed over time. The increasing frequency of dissection to the SMA and identification of the SMA margin by both surgeon and pathologist suggest an increased attention to the SMA margin. This shift did not result in significant improvements in survival or margin status, but it is consistent with the recognition of the importance of the SMA margin. Our analysis has also identified areas of potential improvement in the ways in which operative and pathology reports for PD are generated.

Prospective assessment of midsecretory endometrial leukemia inhibitor factor expression versus ανß3 testing in women with unexplained infertility.

OBJECTIVE: To evaluate endometrial leukemia inhibitor factor (LIF) expression as a marker of endometrial receptivity in women with unexplained infertility (UI). DESIGN: Prospective case-control study. SETTING: University-associated infertility clinics. PATIENT(S): Women with UI for more than 1 year and healthy control women. INTERVENTION(S): Endometrial biopsy. MAIN OUTCOME MEASURE(S): Time to pregnancy was compared between patients with UI who were evaluated for endometrial LIF protein as well as ανß3 integrin expression. Endometrium was evaluated using immunohistochemistry (IHC) and messenger RNA by real time reverse transcriptase-polymerase chain reaction (PCR) (quantitative real-time reverse transcriptase-PCR) in samples from women with UI as well as healthy control women. RESULT(S): Leukemia inhibitor factor was expressed in epithelial cells in a cyclic fashion in controls, and overall expression in the secretory phase was similar between controls and women with UI, whereas ανß3 integrin expression was reduced. However, using quantitative real-time PCR, LIF messenger RNA abundance was 4.4-fold lower in women with low levels of ανß3 integrin expression compared with samples with normal integrins. By immunohistochemistry, ανß3 integrin expression was always lacking when the histology was out of phase, whereas LIF expression was only negative in a subset of those samples. Reduced endometrial LIF expression was strongly associated with poor reproductive outcomes. CONCLUSION(S): Endometrial LIF expression peaks in the midsecretory phase and is reduced in some women with UI. The use of LIF in combination with ανß3 integrin as biomarkers appears to be superior to integrin testing alone when evaluating endometrial receptivity, primarily because of its earlier pattern of expression during the secretory phase.

Use of positron emission tomography in initial staging of nonsmall cell lung carcinoma: a regional teaching hospital experience.

The ability to accurately diagnose mediastinal lymph node involvement is significantly important in patients with nonsmall cell lung cancer (NSCLC). Positron emission tomography (PET) imaging has become a standard technique to assess lymph node involvement in patients with NSCLC. The purpose of this study is to evaluate the accuracy of PET scan imaging as a mediastinal staging tool in patients with NSCLC at our regional teaching institution. We performed a single-institution, retrospective review of patients diagnosed with NSCLC from January 1, 2006, through December 31, 2007. We included only those patients who underwent computed tomography (CT), PET, and pathologic assessment of mediastinal lymph nodes. Using pathologic assessment as the criterion standard, the overall accuracy, sensitivity, specificity, and positive and negative predictive values of CT and PET were calculated. One hundred seventeen patients were identified for inclusion in the study. The overall accuracy was 81.2 per cent for CT and 91.5 per cent for PET. Sensitivity was 42.1 per cent for CT and 52.6 per cent for PET. Specificity was 88.8 per cent for CT and 99.0 per cent for PET. Positive predictive values were 42.1 per cent for CT and 90.9 per cent for PET; negative predictive values were 88.8 per cent for CT and 91.5 per cent for PET. False-negative result rates were 9.4 per cent for CT and 7.7 per cent for PET; false-positive result rates were 9.4 per cent for CT and 0.9 per cent for PET. Our analysis confirms the use of PET scan imaging in the staging of patients with NSCLC at a regional teaching institution.

Inflammatory myofibroblastic tumor of the breast.

Three patients developed firm, mobile, nontender masses in their breasts. Two were discovered by the patients and one after mammography. Macroscopically, the nodules were firm, circumscribed, yellow on cut sections, and composed of interlacing cytologically bland spindle cells admixed with chronic inflammatory cells, the latter predominantly of lymphocytes and plasma cells. Immunohistochemistry yielded strong smooth-muscle actin reactivity within the spindle cells; 2 lesions were negative for pankeratin, 1 was focally and weakly positive. No lesions were positive for anaplastic lymphoma kinase-1, desmin, S-100, CD34, CD21, or CD35. In each case, a diagnosis of inflammatory myofibroblastic tumor was made (aka, inflammatory pseudotumor). After conservative excision with apparently negative margins, there have been no recurrences, except in one patient who developed a recurrence after 3 months. The latter recurrence was managed successfully with a second excision. We report these patients to emphasize the diagnostic features of inflammatory myofibroblastic tumor of the breast and discuss how they can be distinguished from other spindle-cell breast lesions with which they can be confused, especially spindle-cell carcinoma.