Robin H. Amirkhan

The diagnostic accuracy of mammography in the evaluation of male breast disease

BACKGROUND The role of mammography in the evaluation of male patients presenting with breast disease is controversial. This controversy is a function of the lack of specific data concerning the diagnostic accuracy of mammography when used in this clinical setting. The purpose of this study was to define the diagnostic accuracy of mammography in the evaluation of male breast disease. METHODS One hundred and four prebiopsy mammograms from 100 patients with tissue diagnoses were read blindly by two independent radiologists, and placed into one of five predetermined categories: definitely malignant, possibly malignant, gynecomastia, benign mass, and normal. Radiologic/pathologic correlation was performed and the sensitivity (Sn), specificity (Sp), positive (Ppv) and negative predictive value (Npv), and accuracy (Ac) for each of the mammographic diagnostic category determined. RESULTS The pathologic diagnoses were 12 cancers, including 1 patient with bilateral breast cancer, 70 cases of gynecomastia, 16 benign masses, and 6 normals. The accuracy data for the mammographic diagnostic categories are as follows: malignant (combined definitely and possibly malignant), Sn 92%, Sp 90%, Ppv 55%, Npv 99%, Ac 90%; and overall benignity (combined gynecomastia, benign mass, and normal), Sn 90%, Sp 92%, Ppv 99%, Npv 55%, Ac 90%. Six cancers (50%) coexisted with gynecomastia. CONCLUSIONS Mammography can accurately distinguish between malignant and benign male breast disease. Although not a replacement for clinical examination, its routine use could substantially reduce the need for biopsy in patients whose mammograms and clinical examination suggest benign disease.

Inhibin alpha distinguishes hemangioblastoma from clear cell renal cell carcinoma.

Inhibin alpha subunit (inhibin A) expression in hemangioblastomas has not been previously reported in the literature. We analyzed the expression of inhibin A in 25 hemangioblastomas from 22 patients. Eleven cases were from 8 patients with von Hippel-Lindau disease, and these tumors were multicentric and/or recurrent. The remaining 14 cases from 14 patients were sporadic. The male-to-female ratio was 8:3, and the age at presentation ranged from 19 to 78 years (mean 35 years; median 45 years). Eighteen tumors were located in the cerebellum/posterior fossa, 1 in the medulla, 1 in the occipital lobe, and 5 in the spinal cord. Four metastatic renal cell carcinomas in brain, 10 renal cell carcinomas from 8 patients with von Hippel-Lindau disease, and 5 sporadic clear cell renal cell carcinomas were also included. Two patients with von Hippel-Lindau disease had both renal cell carcinoma and hemangioblastoma. The stromal cells of all 25 cases of hemangioblastoma expressed inhibin A. Strong, moderate, and weak cytoplasmic immunoreactivity was noted in 17, 5, and 3 cases, respectively. In contrast, none of the 19 renal cell carcinomas, primary as well as metastatic, expressed inhibin A. There was no difference in the inhibin A staining pattern between the sporadic hemangioblastoma and those associated with VHL. These findings demonstrate inhibin A to be a useful marker in distinguishing hemangioblastoma from metastatic clear cell renal cell carcinoma. While the diagnostic importance is evident, the pathophysiology of inhibin A expression by the stromal cells of hemangioblastoma remains unknown and further investigation is required.

Malignant Melanoma With a Rhabdoid Phenotype: Histologic, Immunohistochemical, and Ultrastructural Study of a Case and Review of the Literature

Malignant melanoma is known to display tremendous histologic diversity. One rare variant is the rhabdoid phenotype, so called because of the appearance of cells resembling rhabdomyoblasts seen in malignant rhabdoid tumors of the kidney. We present the histologic, immunohistochemical, and ultrastructural features of a malignant melanoma composed entirely of rhabdoid cells. A 62-year-old man presented with a 6.5-cm lung mass. Although presumed to be a metastatic lesion, extensive workup failed to reveal a primary tumor site. Histologic sections showed a mass composed entirely of polygonal neoplastic cells with prominent nucleoli and large hyaline cytoplasmic inclusions. The tumor cells were strongly immunoreactive with S100 protein, vimentin, and CD56, and were focally reactive with Mart-1. Tumor cells were negative for Melan-A, tyrosinase, HMB-45, AE1/AE3, cytokeratin (CK) 7, CK8/ 18, CK20, CK903, CAM 5.2, epithelial membrane antigen, smooth muscle actin, desmin, leukocyte common antigen, Bcl-2, CD3, CD20, CD30, CD138, kappa and lambda light chains, CD68, CD34, factor VIII, synaptophysin, and glial fibrillary acidic protein. Electron microscopy showed cytoplasmic whorls of intermediate filaments containing entrapped rough endoplasmic reticulum, mitochondria, and lipid. Recognition of this rare variant of malignant melanoma is important in the evaluation of tumors with rhabdoid morphology.

Cystic Sebaceous Neoplasms in Muir-Torre Syndrome

Cystic sebaceous neoplasms have been seen only in patients with Muir-Torre syndrome (MTS) and have recently been characterized as marker lesions of MTS. Histologically, these lesions form a spectrum of tumors ranging from benign cystic adenomas to proliferative cystic sebaceous tumors. We describe 2 proliferative cystic sebaceous tumors in a 53-year-old man whose workup revealed colonic adenocarcinoma and other sebaceous tumors consistent with MTS. Both the chest wall and the left thigh masses were grossly cystic, measuring 1.0 and 1.5 cm, respectively. Histologic sections demonstrated well-circumscribed cystic neoplasms located in the deep dermis and subcutaneous tissue. Each had a focally infolded cyst wall composed of immature basaloid cells with prominent nucleoli and mitoses, consistent with a proliferative cystic sebaceous tumor. Recognition of cystic sebaceous neoplasm by pathologists and communication to clinicians of its strong association with MTS is of diagnostic importance.

Survival in small cell lung carcinoma is independent of Bcl-2 expression.

Bcl-2 overexpression is a common event in small cell carcinomas (SCLC). The bcl-2 oncoprotein has a unique oncogenic role by inhibiting programmed cell death (apoptosis), resulting in tumorigenesis and chemoresistance. Forty-two cases of SCLC were stained immunohistochemically with bcl-2 monoclonal antibody (Biogenex, San Ramon, CA) after using an antigen retrieval step with citrate buffer. bcl-2 positivity was determined as detection of the oncoprotein in greater than 10% of noncrushed neoplastic cells. Twenty-five of 42 (60%) patients had extensive disease at presentation, 10 of 42 (24%) had limited disease, and 7 of 42 (16%) had disease localized to the lung. Twenty-four of 42 (57%) tumors were bcl-2 positive, and 18 of 42 (43%) tumors were bcl-2 negative. Follow-up in patients ranged from 7 days to 96 months (mean follow-up, 20 months). The median survival of patients with bcl-2-positive tumors was 11 months, as opposed to 13 months for bcl-2-negative tumors. There was no significant difference in median survival between bcl-2-positive and bcl-2-negative SCLC (log rank test, P = .2256). Using Coxs proportional hazards model, median survival in SCLC was determined to be independent of age at diagnosis, stage at presentation, therapeutic modality, and bcl-2 expression. bcl-2 expression does not significantly influence survival in SCLC.

Rosette formation within a proliferative nodule of an atypical combined melanocytic nevus in an adult.

&NA; Rosette formation is a feature that has not been described as occurring in melanocytic neoplasms. We present such a unique case. A 59‐year‐old man presented with an asymptomatic, soft, hairy 3.0 × 2.0‐cm pigmented lesion that had been present for many years in the right external ear, extending from the conchal bowl onto the antitragus area. Examination of histologic sections showed a proliferation of nonatypical and heavily pigmented melanocytes in the superficial dermis and around deep adnexal structures, characteristic of a congenital nevus. In other areas, pigmented spindled and dendritic cells infiltrated thickened collagen bundles in a pattern of a blue nevus. A nodular proliferation of epithelioid melanocytes was seen within the deep dermis and subcutaneous tissue. The periphery of the nodule merged with the surrounding nevus cells. Neoplastic cells with nuclear atypia, melanin pigment, pseudonuclear inclusions, and balloon cell change were present. In addition, there was rosette formation by the tumor cells, with a central aggregate of coarse cell processes. Neuroid cords were also noted. No prominent mitotic figures, necrosis, or significant inflammatory infiltrate were noted. The neoplastic cells were positive for S‐100 protein, Mart‐1, tyrosinase, neuron‐specific enolase, and vimentin. HMB‐45 and Ki‐67 (MIB‐1) labeled only rare neoplastic cells within the proliferative nodule. The tumor cells were negative for synaptophysin, protein gene product 9.5, CD57, epithelial membrane antigen, CD31, and CD34. The central cell processes of the rosettes were negative for trichome, type IV collagen, neurofilament protein, glial fibrillary acidic protein, and tyrosine hydroxylase. We also retrospectively examined 78 congenital nevi of 65 pediatric patients at our institution. Rosette formation was not seen in any of these cases.

Phosphorylated histone H3, Ki-67, p21, fatty acid synthase, and cleaved caspase-3 expression in benign and atypical granular cell tumors.

CONTEXT Granular cell tumors (GCTs) are classified as benign when none of the following features is present: spindling of the tumor cells, necrosis, diffuse pleomorphism, prominent nucleoli, high nuclear-cytoplasmic ratio, and mitotic rate >2 per 10 high-power fields. It has been suggested that a GCT be classified as atypical when 1 or 2 of these features are seen and as malignant when 3 or more of these are present. In our practice, we do not classify GCTs as malignant in the absence of metastasis. OBJECTIVE To compare immunohistochemical staining for phosphorylated histone H3 (PHH3), Ki-67 (MIB-1), p21, fatty acid synthase, and cleaved caspase-3 in histologically classified benign and atypical GCTs. DESIGN We reviewed 25 cases of GCT from our archives and classified 14 as atypical based on histologic features. Immunohistochemical staining for PHH3, Ki-67, p21, fatty acid synthase, and cleaved caspase-3 was performed using standard methods. The number of positive cells for Ki-67, p21, and PHH3 was calculated in 10 consecutive high-power fields in a hot spot. Fatty acid synthase and cleaved caspase-3 cytoplasmic expression was graded from 1 to 3. RESULTS Ki-67 and PHH3 scores were significantly higher in atypical GCTs. The expression of p21, fatty acid synthase, and cleaved caspase-3 was not significantly different between atypical and benign GCTs. CONCLUSIONS This study shows that histologic features are reliable in identifying GCTs that have a higher proliferative potential as shown by higher immunoreactivity for Ki-67 and PHH3. These immunostains may help in classifying GCTs in cases where a thorough histologic evaluation is precluded by the small size of a biopsy specimen.

Impact of Inadequate Empiric Antimicrobial Therapy on Clinical Outcomes of Patients With Escherichia coli or Klebsiella Species Bacteremia

This study was conducted to evaluate the effect of inadequate empiric antimicrobial therapy (IEAT) on mortality of patients with Escherichia coli or Klebsiella species bacteremia. Patients with E coli or Klebsiella species bacteremia were retrospectively analyzed to determine the effect of IEAT on 14-day mortality. IEAT of bacteremia was defined as administration of an antimicrobial agent to which the microorganism responsible for the bacteremia was resistant. IEAT was significantly associated with central venous catheter placement, Klebsiella species, and antimicrobial resistance among the 135 patients with E coli or Klebsiella species bacteremia (110 adequate, 25 inadequate). IEAT significantly increased 14-day mortality (32% vs 19%; P = .019). The increased 14-day mortality associated with IEAT was consistent among patients infected with E coli (33% vs 11%) or Klebsiella species (31% vs 15%). Independent risk factors for 14-day mortality in the multivariate analysis included Acute Physiology and Chronic Health Evaluation II (APACHE II) score (odds ratio [OR] 1.16; 95% confidence interval [CI] = 1.07-1.27), IEAT (OR 9.4; 95% CI = 1.36-65.14), and initial imipenem therapy (OR 20.66; 95% CI = 1.48-287.74). Of the 6 patients receiving empiric imipenem/cilastatin, 3 had APACHE II scores ≥ 30 (all 3 of these patients died). The 14-day mortality rate was similar for patients who received IEAT, regardless of whether their therapy was changed (32%) or not (33%). Based on these results and previous studies, greater efforts should be made to identify patients at risk for resistant pathogens before initiating antimicrobial therapy.

Eosinophilic lung disease associated with non-Hodgkin lymphoma: A case report and review of the literature

Eosinophilic lung diseases have many causes but are not often the result of neoplastic disease. We describe a patient with subacute dyspnea due to eosinophilic lung disease who also had a peripheral T-cell lymphoma. The diagnosis was made by imaging and transbronchial biopsies of the lungs along with an excisional biopsy of a palpable epitrochlear lymph node. There is a rare association between eosinophilic pneumonias and non-Hodgkin lymphomas. This is the third known case of a peripheral T-cell lymphoma associated with eosinophilic lung disease. This report highlights the association, discusses theorized mechanisms involved, and emphasizes the importance of searching for underlying etiologies for eosinophilic lung disease.

A case of gastrointestinal zygomycosis in a patient with gastric adenocarcinoma

Abstract: Zygomycosis, in particular, infection due to fungi of the order Mucorales, is typically found in patients with diabetes, solid organ transplants, hematologic malignancies, or those treated with deferoxamine. Recently, with increased myleosuppressive chemotherapy regimens, more cases of pulmonary or disseminated zygomycosis have been reported in neutropenic patients than in the past. We present a white man diagnosed with gastric adenocarcinoma who presented with a small bowel perforation due to gastrointestinal zygomycosis. He was not significantly neutropenic, however, his risk for development of this unusual fungal infection was malnutrition, acidosis, and leukopenia.