Two case reports of fulminant giant cell myocarditis treated with rabbit anti-thymocyte globulin.

Background: Giant cell myocarditis (GCM) is an inflammatory form of acute heart failure with high rates of cardiac transplantation or death. Standard acute treatment includes multi-drug immunosuppressive regimens. There is a small but growing number of case reports utilizing rabbit anti-thymocyte globulin in severe cases. Case summary: Two cases are presented with similar presentations and clinical courses. Both are middle-aged patients with no significant past medical history, who presented with new acute decompensated heart failure that quickly progressed to cardiogenic shock requiring inotropic and mechanical circulatory support. Both underwent endomyocardial biopsies that diagnosed GCM. Both were treated with a multi-agent immunosuppressive regimen, notably including rabbit anti-thymocyte globulin, with subsequent resolution of shock and recovery of left ventricular ejection fraction. Both remain transplant-free and without ventricular arrhythmias at 7 months and 26 months, respectively. Discussion: In aggregate, these cases are typical of GCM. They add to growing observational data that upfront rabbit anti-thymocyte globulin may reduce morbidity and mortality in GCM, including potentially preventing the need for complex interventions like orthotopic heart transplantation.

Glottic myxoma presenting as chronic dysphonia: a case report and review of the literature.

Myxomas of the vocal fold are rare benign tumors often presenting with chronic dysphonia and less frequently with airway obstruction. The current consensus is that all laryngeal myxomas should be totally excised with clear margins to prevent recurrences. The recommendation for complete excision, however, has to be balanced with consideration of preserving vocal fold phonatory and sphincteric function. We report a case of vocal fold myxoma recurring twice after subtotal excision via two surgical approaches. This case illustrates a benign lesion with potential for recurrence and the need for a balanced treatment approach.

The coccidioidomycosis conundrum: a rare parotid mass.

A man, age 62 years, presented to the clinic with a 2-week history of increased nontender, nonerythematous, indurated right-sided parotid swelling. A 4 × 6-cm firm, well-circumscribed mass was palpated in the right parotid gland. A fine-needle aspiration biopsy was performed on the parotid mass with aspiration of 0.5 cc of purulent fluid with some blood. Cultures from the aspirate revealed Coccidioides immitis confirmed by DNA probe. Pathology slides revealed fungal spores. The patient was treated with 800 mg of fluconazole every day for 3 months with resolution of the parotid swelling. However, persistent cervical adenopathy remains.Although this is a rare case of acute parotid swelling, Coccidioides immitis should be considered in the differential diagnosis of parotid masses in a patient with previous coccidioidomycosis. There may be a potential for an increase in frequency and variety of atypical extrapulmonary manifestations of coccidioidomycosis that parallels the increase in coccidioidomycotic pulmonary infections. Long-term antifungal therapy appears essential for control.

A novel sarcoma with dual differentiation: clinicopathologic and molecular characterization of a combined synovial sarcoma and extraskeletal myxoid chondrosarcoma.

We report on an unusual case of a 43-year-old woman who developed a malignant soft tissue tumor of the arm with overlapping morphology between synovial sarcoma (SS) and extraskeletal myxoid chondrosarcoma (EMC). The tumor recurred 7 years after the initial diagnosis and continued to demonstrate both SS and EMC histology. Immunophenotypically, the primary and recurrent tumors were both positive, focally, for cytokeratin, S-100, bcl-2, and epithelial membrane antigen. At the time of recurrence, the primary and recurrent tumors were further characterized for genetic and molecular abnormalities. Intriguingly, fluorescence in situ hybridization of the primary tumor revealed rearrangements of both the SS18 and EWSR1 genes. Furthermore, reverse transcriptase-polymerase chain reaction studies of both the primary tumor and the recurrence confirmed the presence of both SS18-SSX2 and EWSR1-NR4A3 (exon 3) gene fusions, characteristic of SS and EMC, respectively. This is the first reported case of a remarkable soft tissue sarcoma that exhibits overlapping morphologic features between SS and EMC and that also harbors a combination of SS18-SSX2 and EWS-NR4A3 gene fusions. This case supports the fact that specific, reproducible gene fusions frequently direct, cooperatively or competitively, basic histogenetic processes to produce tumor phenotypes.

Mammographic density and risk of second breast cancer after ductal carcinoma in situ.

BACKGROUND: We examined whether mammographic density predicts risk of second breast cancers among patients with ductal carcinoma in situ (DCIS). METHODS: The study included DCIS patients diagnosed during 1990 to 1997 and treated with breast-conserving surgery at Kaiser Permanente Northern California. Medical records were reviewed for clinical factors and subsequent breast cancers (DCIS and invasive). Ipsilateral mammograms from the index DCIS were assessed for density without knowledge of subsequent cancer status. Cox regression modeling was used to examine the association between mammographic density and risk of breast cancer events. RESULTS: Of the 935 eligible DCIS patients, 164 (18%) had a subsequent ipsilateral breast cancer, and 59 (6%) had a new primary cancer in the contralateral breast during follow-up (median, 103 mo). Those with the greatest total area of density (upper 20% of values) were at increased risk for invasive disease in either breast [hazard ratio (HR), 2.1; 95% confidence interval (95% CI), 1.2-3.8] or any cancer (DCIS or invasive) in the ipsilateral (HR, 1.7; 95% CI, 1.0-2.9) or contralateral (HR, 3.0; 95% CI, 1.3-6.9) breast compared with those with the smallest area of density (bottom 20%). HRs for these same end points comparing those in the highest with those in the lowest American College of Radiology Breast Imaging Reporting and Data System category were 1.6 (95% CI, 0.7-3.6), 1.3 (95% CI, 0.7-2.6), and 5.0 (95% CI, 1.4-17.9), respectively. There was a suggestion of increasing risk of contralateral, but not ipsilateral, cancer with increasing percent density. CONCLUSIONS: Women with mammographically dense breasts may be at higher risk of subsequent breast cancer, especially in the contralateral breast. IMPACT: Information about mammographic density may help with DCIS treatment decisions.

Relationship between clinical and pathologic features of ductal carcinoma in situ and patient age: an analysis of 657 patients.

Prior studies have shown that young patient age at diagnosis is associated with an increased risk of local recurrence among women with ductal carcinoma in situ (DCIS) treated with breast-conserving therapy. Whether this can be explained by differences in clinical or pathologic features of DCIS according to age is an unresolved issue. We compared clinical and pathologic features of DCIS among 657 women in 4 age groups: <45 years (n=111), 45 to 54 years (n=191), 55 to 64 years (n=160), and 65+ years (n=195). DCIS presented as a mammographic abnormality less often in younger than in older women (68%, 82%, 81%, and 86% for women <45, 45 to 54, 55 to 64, and 65+ y, respectively; P=0.003). Among the pathologic features analyzed, DCIS extent as determined by the number of low power fields was greater in younger than in older women (mean number of low power fields were 18.6, 14.2, 10.8, and 11.3 in women <45, 45 to 54, 55 to 64 and 65+ y; P<0.001). In addition, cancerization of lobules was present more often in younger than in older women (77%, 73%, 66%, and 50% for women <45, 45 to 54, 55 to 64 and 65+ y, respectively; P<0.0001). Of note, we found no statistically significant relationship between age and DCIS architectural pattern, nuclear grade, comedo necrosis or expression of estrogen receptor, progesterone receptor or human epidermal growth factor receptor 2. We conclude that DCIS in younger women is more often symptomatic, is more extensive, and more often shows cancerization of lobules than DCIS in older women. Whether these features contribute to the higher local recurrence risk in young women with DCIS treated with the breast-conserving therapy requires further study.

Declining recurrence among ductal carcinoma in situ patients treated with breast-conserving surgery in the community setting.

INTRODUCTION: Randomized trials indicate that adjuvant radiotherapy plus tamoxifen decrease the five-year risk of recurrence among ductal carcinoma in situ patients treated with breast-conserving surgery from about 20% to 8%. The aims of this study were to examine the use and impact of these therapies on risk of recurrence among ductal carcinoma in situ patients diagnosed and treated in the community setting. METHODS: We identified 2,995 patients diagnosed with ductal carcinoma in situ between 1990 and 2001 and treated with breast-conserving surgery at three large health plans. Medical charts were reviewed to confirm diagnosis and treatment and to obtain information on subsequent breast cancers. On a subset of patients, slides from the index ductal carcinoma in situ were reviewed for histopathologic features. Cumulative incidence curves were generated and Cox regression was used to examine changes in five-year risk of recurrence across diagnosis years, with and without adjusting for trends in use of adjuvant therapies. RESULTS: Use of radiotherapy increased from 25.8% in 1990-1991 to 61.3% in 2000-2001; tamoxifen increased from 2.3% to 34.4%. A total of 245 patients had a local recurrence within five years of their index ductal carcinoma in situ. The five-year risk of any local recurrence decreased from 14.3% (95% confidence interval 9.8 to 18.7) for patients diagnosed in 1990-1991 to 7.7% (95% confidence interval 5.5 to 9.9) for patients diagnosed in 1998-1999; invasive recurrence decreased from 7.0% (95% confidence interval 3.8 to 10.3) to 3.1% (95% confidence interval 1.7 to 4.6). In Cox models, the association between diagnosis year and risk of recurrence was modestly attenuated after accounting for use of adjuvant therapy. Between 1990-1991 and 2000-2001, the proportion of patients with tumors with high nuclear grade decreased from 46% to 32% (P = 0.03) and those with involved surgical margins dropped from 15% to 0% (P = 0.03). CONCLUSIONS: The marked increase in the 1990s in the use of adjuvant therapy for ductal carcinoma in situ patients treated with breast-conserving surgery in the community setting only partially explains the 50% decline in risk of recurrence. Changes in pathology factors have likely also contributed to this decline.

Multiple proinsulin-secreting tumors of the pancreas treated by laparoscopic distal pancreatectomy and splenectomy.

BACKGROUND: Patients with pancreatic tumors that induce hypoglycemia present with a myriad of symptoms. Laboratory testing can frequently result in data challenging to the clinician to confirm the biochemical diagnosis. Proinsulin, in addition to insulin levels, may be essential in evaluating and diagnosing an insulinoma. METHODS: The objective of this case report is to demonstrate the potential importance of proinsulin levels in the evaluation of tumor-induced hypoglycemia. We report a 49-year-old woman with an unusual clinical presentation. Unlike many patients with tumor-induced hypoglycemia, her fasting glucose levels were fairly unimpressive, her insulin levels were undetectable during a prolonged fast, and she had elevated proinsulin levels. RESULTS: The inpatient fast was remarkable for levels of serum glucose 53 mg/dl or higher, a serum insulin <2 uIU/ml, C-peptide 0.7-1.1 (nl 0.8-3.1 ng/ml), and proinsulin 29.2-36.8 pmol/l (nl < or = 18.8 pmol/l). CT scanning of the abdomen revealed multiple pancreatic lesions. A laparoscopic distal pancreatectomy led to the removal of multiple neuroendocrine tumors, which stained only for proinsulin and not for other pancreatic tumor markers. Postoperatively, she normalized her biochemical serum studies and has remained symptom-free 2 years later. CONCLUSIONS: The measurement of proinsulin plays an important part in the diagnostic workup of neuroendocrine tumors causing hypoglycemia. These potentially malignant tumors can be treated adequately with minimally invasive surgery.

Clinical and pathologic features of ductal carcinoma in situ associated with the presence of flat epithelial atypia: an analysis of 543 patients.

Flat epithelial atypia is an alteration of mammary terminal duct lobular units that is considered to be a precursor to, or early stage in, the development of some forms of ductal carcinoma in situ. No prior study has systematically evaluated the relationship between various clinico-pathologic features of ductal carcinoma in situ and the presence of coexistent flat epithelial atypia. An understanding of such relationships could provide insight into the connection between flat epithelial atypia and ductal carcinoma in situ. We reviewed slides from 543 ductal carcinoma in situ patients enrolled in a case-control study assessing epidemiologic and pathologic risk factors for local recurrence. We examined the association between the presence of flat epithelial atypia and various clinical factors, pathologic features of the ductal carcinoma in situ, and the presence of coexistent atypical ductal hyperplasia, lobular neoplasia, and non-atypical columnar cell lesions. In univariate analysis, the presence of flat epithelial atypia was significantly related to ductal carcinoma in situ nuclear grade (most common in low grade, least common in high grade; P<0.0001), architectural pattern (most common in micropapillary and cribriform, least common in comedo; P<0.0001), absence of comedo necrosis (P<0.001), absence of stromal desmoplasia (P=0.02) and absence of stromal inflammation (P=0.03). In multivariable analysis, features of ductal carcinoma in situ independently associated with flat epithelial atypia were micropapillary and cribriform patterns and absence of comedo necrosis. Additionally, flat epithelial atypia was significantly associated with the presence of atypical ductal hyperplasia, lobular neoplasia, and columnar cell lesions in both univariate and multivariable analyses. These observations provide support for a precursor-product relationship between flat epithelial atypia and ductal carcinoma in situ lesions that exhibit particular features such as micropapillary and cribriform patterns and absence of comedo necrosis.

Comparison of ThinPrep versus conventional smear cytopreparatory techniques for fine-needle aspiration specimens of head and neck masses.

OBJECTIVES: Diagnostic accuracy of the ThinPrep process (Cytyc, Boxborough, MA) was compared with that of conventional (smear) cytopreparation for fine-needle aspiration (FNA) of head and neck masses. METHODS: In a prospective, randomized, single-blinded study, 209 patients served as their own controls and underwent 236 FNAs using ThinPrep and conventional (smear) cytopreparatory techniques. RESULTS: ThinPrep produced less air-drying artifact and less mechanical distortion than the conventional method. The conventional technique was diagnostic in 63% of samples; the ThinPrep technique was diagnostic in 55% of samples. When all results were combined, pathologists subjectively preferred the conventional technique but accepted use of ThinPrep as the only cytopreparatory technique for most head and neck masses. CONCLUSIONS: For adequately experienced cytopathologists, ThinPrep is acceptable for FNA of salivary masses, neck cysts, metastatic lymph nodes, and thyroid lesions. Conventional smear technique should be used for FNA of nonmetastatic lymphoid lesions. Use of ThinPrep can complement use of the conventional (smear) cytopreparatory technique when aspirate is nondiagnostic or bloody, when the patient has a blood-borne infectious disease, when the clinician is inexperienced, or when aspirate has entered the syringe.

CagA status of Helicobacter pylori infection and p53 gene mutations in gastric adenocarcinoma.

Infection with Helicobacter pylori (H. pylori) increases stomach cancer risk. Helicobacter pylori strains with the cag pathogenicity island (PAI) induce more severe inflammation in the gastric epithelium and are more strongly associated with stomach cancer risk than strains lacking the PAI. We examined whether the prevalence of somatic p53 mutation in gastric adenocarcinoma differed between subjects with and without infection with CagA(+) (a marker for the PAI) H. pylori strains. DNA from 105 microdissected tumor specimens was analyzed for mutation in exons 5-8 of the p53 gene by polymerase chain reaction-based single-strand conformation polymorphism followed by direct DNA sequencing. Enzyme-linked immunosorbent assays for IgG antibodies against H. pylori and CagA were performed on sera collected 2-31 years prior to cancer diagnosis. Tumors from CagA(+) subjects were significantly more likely to have p53 mutations than tumors from CagA(-) subjects (including H. pylori- and H. pylori(+)/CagA(-)): odds ratio = 3.72; 95% confidence interval, 1.06-13.07 after adjustment for histologic type and anatomic subsite of tumor and age at diagnosis and sex of subjects. Mutations were predominantly insertions and deletions (43%) as well as transition mutations at CpG dinucleotides (33%). The data suggest that CagA(+) H. pylori infection, when compared with CagA(-) infection or the absence of H. pylori infection, is associated with a higher prevalence of p53 mutation in gastric adenocarcinoma.