Histopathologic findings of small renal tumor biopsies performed immediately after cryoablation therapy: a retrospective study of 50 cases.

OBJECTIVES: To evaluate the histopathology of small renal tumor biopsies following cryoablation. METHODS: We retrospectively evaluated small renal tumor biopsy specimens after cryoablation treatment for renal cell carcinoma and determined the ability to differentiate tumor types, effect on nuclear grading, immunohistochemical staining, and if the number of freeze cycles affected interpretation. RESULTS: Of the biopsy specimens, 66% were diagnostic of tumor and 34% showed normal renal parenchyma. Tumor subtype was determined in 91% of diagnostic cases. Nuclear grading was affected due to freeze effect, complicating the assessment of chromatin pattern and nucleolar details at low magnification. In particular, the distinction between Fuhrman nuclear grades I and II was compromised; these were designated as low nuclear grade. Immunohistochemical staining was retained similar to untreated tumors. Tumor subtyping was not affected after one or two freeze cycles. CONCLUSIONS: Biopsies performed immediately after cryoablation can be used to render an optimal histologic diagnosis.

Microscopic colitis. A review.

Microscopic colitis (MC) is characterized by a triad of watery diarrhea, usually normal colonoscopic findings and typical microscopic findings. Two distinct histological forms of MC have been defined: lymphocytic colitis and collagenous colitis, but overlapping features may be present. The incidence of MC appears to be rising and in some countries it may account for as many as 10-20% of patients with non-bloody watery diarrhea. The cause of MC remains unknown and is likely to be multifactorial. The pathogenesis is poorly defined, and numerous immunological abnormalities have been reported. MC is commonly associated with autoimmune diseases including celiac disease. Use of various medications, most notably non-steroidal anti-inflammatory agents and proton pump inhibitors, have been etiologically implicated but not firmly established as causative. In imperfect trials several agents have been reported to be effective in the treatment of MC; budesonide is the best studied and evidence supporting its effectiveness is the most persuasive. In cases of otherwise unexplained watery, non-bloody diarrhea, MC should be considered and colonic biopsied specimens should be taken of normal-appearing mucosa.

Desmoid-type fibromatosis involving the brachial plexus.

Desmoid-type fibromatosis involving the brachial plexus is a rare and challenging disease. Due to involvement of crucial neurovascular structures, wide local excision of the associated fibromas is rarely feasible and recurrence is common. The authors describe their experience in four surgically treated patients with desmoid-type fibromatosis involving the brachial plexus and review the relevant neurosurgical literature. All tumors were assessed for c-KIT oncogene mutations in hopes of establishing a biological basis for using the tyrosine kinase inhibitor imatimib mesylate as an adjuvant therapy. Three patients experienced tumor recurrence requiring reoperation. Fractionated radiotherapy achieved local control in three patients, and the disease in one patient progressed beyond the treatment field. Single base pair changes at exon 10 of the c-KIT oncogene were identified in three tumors. One tumor with this mutation did not respond to treatment with imatimib mesylate. A review of the literature revealed 17 additional patients in two different case series. Analysis of these cases emphasizes the need for careful resection in patients with desmoid-type fibromatosis and supports the conclusion that without adjuvant radiotherapy a high local recurrence rate can be anticipated. For optimal local disease control, the authors recommend postsurgical radiation therapy regardless of the extent of resection achieved. The mutational status of the c-KIT oncogene remains an intriguing biological marker that in the future may predict which lesions will be responsive to imatimib mesylate; larger series will be necessary to test this hypothesis.

Myoepithelial carcinoma of soft tissue: a case report.

Myoepithelioma of soft tissue is a recently categorized entity and myoepithelial carcinoma is extremely rare. We describe a case of myoepithelial carcinoma of soft tissue in a 30-year-old male patient, who presented with a painless mass located at the back of left leg involving popliteal fossa that was present since childhood. A wide local excision was performed. The distinct histopathological features included infiltrative margins, cytologically moderate to severely atypical epithelioid/spindled cells with prominent nucleoli, 3-4 mitoses/10HPF, tumor necrosis and lymphovascular invasion. No heterologous elements were identified. The myoepithelial origin was confirmed by positive immunohistochemical staining for S100 protein, epithelial membrane antigen and smooth muscle actin. Mib-1 (Ki-67) proliferation index was 20-25%. These carcinomas have variable clinical presentation and can have an indolent course for several years. Recognition of myoepithelial carcinoma is clinically significant because compared to its benign counterpart, this has increased frequency of local recurrences and metastases that warrants a close clinical follow-up.

Desmoid-type fibromatoses involving the brachial plexus: treatment options and assessment of c-KIT mutational status.

OBJECT: Desmoid-type fibromatoses are a locally invasive soft-tissue lesion that is most commonly encountered in abdominal sites. The tumor also affects head and neck areas, particularly the supraclavicular region, where it may encase and distort the brachial plexus and compromise neurovascular structures. Neurosurgeons may be called on to treat desmoid-type fibromatoses in these sites. The authors describe their experience in treating four patients with desmoid-type fibromatoses involving the brachial plexus and report the results of immunohistochemical analysis of the tumors. METHODS: Gross-total excision with nerve sparing was the first-line therapy of choice, although the surgery was challenging. Intraoperative identification of the site of tumor origin from musculoaponeurotic tissues by the neurosurgeon was necessary in two of the four cases to achieve a correct frozen section or final pathological diagnosis. Immunostaining for c-KIT (CD117) was undertaken in all cases in light of a previous report of positive CD117 immunoreactivity in abdominal desmoid-type fibromatoses. All four tumors manifested weak focal immunostaining for c-KIT. One of the patients was given adjuvant imatinib mesylate therapy, with limited success. Subsequent polymerase chain reaction testing revealed that three of the four tumors manifested a single base pair change in exon 10 of the c-KIT gene (A to C in two cases and A to G in one case). There was local recurrence in three patients, despite gross-total excision. With the combination of surgery and radiation therapy, local disease control was achieved in three of the four patients. CONCLUSIONS: This represents the first report of c-KIT sequencing in desmoid-type fibromatoses and suggests a possible biological basis for continuing to explore the use of adjuvant imatinib mesylate therapy.

Sarcoidois and pulmonary hypertension--a case report.

We report a case of severe pulmonary hypertension associated with sarcoidosis with a unique histopathological presentation. This 43-year old obese patient first presented eight years ago with complaint of dyspnea on exertion for four years and was diagnosed as primary pulmonary hypertension. Six years later, a skin biopsy performed on her left cheek to rule out squamous cell carcinoma revealed sarcoidosis. The patient was then put on steroid therapy and subsequently, the oxygen saturation improved transiently, although the mean pulmonary arterial pressure did not show improvement. The patient was then started on prostacyclin infusion and was hemodynamically stable, but the pulmonary artery pressures worsened. The patient died from complications subsequent to a diagnostic procedure. An autopsy limited to the lungs was performed and routinely prepared hematoxylin and eosin stained sections were examined. Immunohistochemical stains for CD31, factor VIII-related antigen and muscle-specific actin were performed on selected sections. The diagnosis of sarcoidosis was confirmed. However, pulmonary fibrosis was not seen. The granulomas surrounded medium- and small-sized pulmonary arteries, but did not destroy the vessel wall. Plexiform lesions indicating severe pulmonary hypertension were identified in pulmonary arteries, which were not involved by granulomas.

C-kit expression in dedifferentiated and well-differentiated liposarcomas; immunohistochemistry and genetic analysis.

BACKGROUND: c-kit expression by immunohistochemistry has been utilized to identify cancer patients who can be treated with imatinib-mesylate. In gastrointestinal stromal tumors (GISTs), an activating mutation in c-kit predicts treatment response; its presence in other soft tissue tumors is unexplored. MATERIALS AND METHODS: We evaluated seven cases of dedifferentiated liposarcomas (DDLS) and compared those with seven well-differentiated liposarcomas (WDLS). Immunohistochemical staining for c-kit was performed using a polyclonal antibody. Using PCR, exons 9, 10-11, 12-13 and 17 of c-kit were amplified and direct DNA sequencing performed. RESULTS: Two out of 7 (30%) DDLS showed focal weak immunoreactivity with c-kit; no (0%) WDLS stained with c-kit. Seven out of 7 (100%) DDLS showed an allelic variation in exon 10, with a single base pair substitution (A >C) at codon 541; 3/7 (43%) WDLS showed the same change. CONCLUSION: c-kit immunoreactivity did not correlate with the change in DNA sequence; DDLS showed a consistent allelic variation in c-kit that may have significant prognostic, diagnostic and therapeutic implications.

Endothelial nitric oxide synthase-deficient mice exhibit increased susceptibility to endotoxin-induced acute renal failure.

Acute renal failure (ARF) in septic patients drastically increases the mortality to 50-80%. Nitric oxide (NO) has been shown to be increased in sepsis. Endothelial nitric oxide synthase (eNOS) is one of the major regulators of arterial blood pressure and regional blood flow; however, its in vivo role in septic ARF is still unclear. We hypothesized that eNOS affords a protective effect against the renal vasoconstriction during endotoxemia. Because there are no specific inhibitors for eNOS, the study was therefore undertaken in eNOS knockout mice. There was no significant difference in baseline glomerular filtration rate (GFR) between the wild-type mice and the eNOS knockout mice (140 +/- 10 vs. 157 +/- 18 microl/min, n = 9, P = not significant). However, renal blood flow (RBF) was significantly decreased in eNOS knockout mice compared with the wild-type controls (0.62 +/- 0.05 ml/min, n = 6 vs. 0.98 +/- 0.13 ml/min, n = 8, P < 0.05). Mean arterial pressure (MAP) was significantly higher in eNOS knockout mice than the wild-type controls (109 +/- 5 vs. 80 +/- 1 mmHg, n = 10, P < 0.01). Thus renal vascular resistance (RVR) was much higher in eNOS knockout mice than in the wild-type mice (176 +/- 2, n = 6 vs. 82 +/- 1 mmHg.ml(-1).min(-1), n = 8, P < 0.01). When 1.0 mg/kg LPS was injected, there was no change in MAP in either the wild-type (84 +/- 3 mmHg, n = 10) or the eNOS knockout mice (105 +/- 5 mmHg, n = 10). Although GFR (154 +/- 22 microl/min, n = 8) and RBF (1.19 +/- 0.05 ml/min, n = 9) remained unchanged with the 1.0-mg/kg dose of LPS in the wild-type mice, GFR (83 +/- 18 vs. 140 +/- 10 microl/min, n = 6, P < 0.01) and RBF (0.36 +/- 0.04 vs. 0.62 +/- 0.05 ml/min, n = 6, P < 0.01) decreased significantly in the eNOS knockout mice. Fractional excretion of sodium increased significantly in eNOS knockout mice during endotoxemia (3.61 +/- 0.78, n = 7 vs. 0.95 +/- 0.14, n = 6, P < 0.01), whereas it remained unchanged in the wild-type mice (0.59 +/- 0.16, n = 9 vs. 0.42 +/- 0.05, n = 6, P = not significant). In summary, eNOS knockout mice have increased RVR and are more susceptible to endotoxemic ARF than wild-type mice despite higher MAP.

Vancomycin-associated linear IgA bullous dermatosis mimicking toxic epidermal necrolysis.

Vancomycin is the most frequent trigger of drug-induced linear IgA bullous dermatosis. We describe a fulminant case of linear IgA bullous dermatosis in a 74-year-old man who experienced skin sloughing of 90% of his body surface after receiving vancomycin.