Expanding the pathologic spectrum of immunoglobulin light chain proximal tubulopathy.

CONTEXT: In plasma cell dyscrasias, involvement of the distal tubules is frequent and well characterized. In contrast, proximal tubules have only rarely been reported to show diagnostic pathology such as intracytoplasmic crystals. OBJECTIVE: To look for additional morphologic features that might be helpful in the diagnosis of proximal tubulopathy associated with an underlying plasma cell dyscrasia. DESIGN: We examined patients presenting with nonspecific renal symptoms who were found to have light chain restriction limited to proximal tubular epithelium by immunofluorescence. We correlated these results with light microscopy, electron microscopy, and the clinical findings. RESULTS: By immunofluorescence, 5 patients had light chain restriction in proximal tubular epithelium. By light microscopy, only 1 patient had focal rhomboid crystals in the proximal tubular epithelium; all other biopsies failed to show any discernible pathology within the proximal tubules or elsewhere in the kidney. By electron microscopy, proximal tubules from 2 patients showed crystals with a latticelike structure, whereas the remaining 3 patients had only prominent phagolysosomes. However, by immunoelectron microscopy, the lysosomal content showed light chain restriction (in 2 cases studied). Post-kidney biopsy, all patients were diagnosed with multiple myeloma or plasma cell dyscrasia. One patient developed renal failure and had recurrence of crystals in the allograft. CONCLUSIONS: Light chain proximal tubulopathy may be associated with the presence of crystals or with the presence of phagolysosomes with light chain restriction as the sole abnormality. Both kappa and lambda light chains may be involved. The prognosis is variable and the pathology may recur in transplants.

Spindle cell tumors of the pleura: differential diagnosis.

Spindle cell tumors that arise in or metastasize to the pleura must be thoroughly evaluated to arrive at a definitive diagnosis. Malignant mesothelioma is the most common tumor arising in the pleura, but metastatic tumors to the pleura occur more frequently. Additionally, many tumors arising in the lung and surrounding tissues involve the pleura. It is crucial to arrive at a correct diagnosis since many of these neoplasms show different prognoses and require varying treatment modalities. Sarcomatoid malignant mesothelioma is a rare tumor that arises in the pleura, and can be confused with numerous tumors arising in or metastasizing to the pleura, including synovial sarcoma, metastatic sarcomatoid carcinoma, metastatic melanoma, thymoma, renal cell carcinoma, localized fibrous tumor, leiomyosarcoma, and other types of sarcoma. Desmoplastic malignant mesothelioma is a fibrous sarcomatoid variant of malignant mesothelioma, and is occasionally mistaken for chronic fibrous pleurisy. Here, we review morphological, clinical, histological, immunohistochemical, ultrastructural, and molecular methods that aid in the diagnosis of spindle cell tumors of the pleura, and we provide specific examples of patients in which this multi-modal approach proved to be helpful.

Diminished induction of skin fibrosis in mice with MCP-1 deficiency.

Scar and fibrosis are often the end result of mechanical injury and inflammatory diseases. One chemokine that is repeatedly linked to fibrotic responses is monocyte chemoattractant protein-1 (MCP-1). We utilized a murine fibrosis model that produces dermal lesions similar to scleroderma to evaluate collagen fibrillogenesis in the absence of MCP-1. Dermal fibrosis was induced by subcutaneous injection of bleomycin into the dorsal skin of MCP-1-/- and wild-type C57BL/6 mice. After 4 weeks of daily injections, bleomycin treatment led to thickened collagen bundles with robust inflammation in the lesional dermis of wild-type mice. In contrast, the lesional skin of MCP-1-/- mice exhibited a dermal architecture similar to phosphate-buffered saline (PBS)-injected control and normal skin, with few inflammatory cells. Ultrastructural analysis of the lesional dermis from bleomycin-injected wild-type mice revealed markedly abnormal arrangement of collagen fibrils, with normal large diameter collagen fibrils replaced by small collagen fibrils of 41.5 nm. In comparison, the dermis of bleomycin-injected MCP-1-/- mice displayed a uniform pattern of fibril diameters that was similar to normal skin (average diameter 76.7 nm). The findings implicate MCP-1 as a key determinant in the development of skin fibrosis induced by bleomycin, and suggest that MCP-1 may influence collagen fiber formation in vivo.

Metastatic juxtaglomerular cell tumor in a 52-year-old man.

Juxtaglomerular cell tumor is a rare renal neoplasm arising from the juxtaglomerular apparatus. Approximately 70 cases have been reported in the English literature since it was first described by Robertson et al in 1967. This tumor has been considered benign and resection has so far been curative. In this paper, we report the first metastatic juxtaglomerular cell tumor. The 15-cm tumor occurred in the right kidney of a 46-year-old man. It invaded the renal vein, and was treated by radical nephrectomy in 1995. The diagnosis at that time was renal cell carcinoma. The patient was well for 6 years and then developed bilateral lung masses, which were resected. Microscopically, the tumors from the kidney and the lungs were similar, consisting of solid sheets of uniformly round-to-polygonal cells intermixed with abundant delicate vasculature. Both renal and pulmonary tumors were positive for vimentin, renin, and only focally to CD34. Electron microscopic studies performed on the paraffin-embedded renal tumor and formalin-fixed lung tumor revealed the typical rhomboid crystals of proto-renin. In consideration of the characteristic morphologic features, immunohistochemistry, and the presence of rhomboid crystals of proto-renin, the diagnosis was modified to malignant juxtaglomerular cell tumor.

Heart transplantation in a patient with chloroquine-induced cardiomyopathy.

We present the first report of a patient who underwent heart transplantation (HT) after endomyocardial biopsy (EMB) and revealed chloroquine-induced cardiomyopathy (CIC). This patient, who was treated with chloroquine for 6 years, developed a restrictive cardiomyopathy that progressed to congestive heart failure (CHF) resistant to medical management.

Molecular analyses, morphology and immunohistochemistry together differentiate pleural synovial sarcomas from mesotheliomas: clinical implications.

BACKGROUND: Only recently pleural synovial sarcomas (SS) have been definitively identified because of the presence of a characteristic X;18 translocation. SS are sarcomatoid or biphasic malignancies morphologically almost indistinguishable from sarcomatoid or biphasic malignant mesotheliomas (MM). PATIENT AND METHODS: We demonstrated a primary pleural biphasic SS in a patient referred to us has having a biphasic MM. RESULTS: Histology showed a spindle cell tumor with focal epithelioid differentiation, microcalcifications, and a hemangiopericytomatous vascular pattern. Ultrastructurally, the epithelioid tumor cells had few blunt microvilli and occasional intercellular junctions. Immunohistochemically the tumor cells were positive for BCL-2, CD99, CD56, and focally for BerEp4, Pancytokeratin and cytokeratin 5/6. These findings suggested the possibility of SS rather than MM. Detection of the t(X:18) translocation using RT-PCR, Southern blot, and DNA sequencing definitively confirmed the diagnosis of SS. CONCLUSION: The differential between pleural SS and MM requires a high degree of suspicion and molecular analyses because morphology (histology, immunohistochemistry and electron microscopy) is insufficient to definitively distinguish between these two malignancies. This differential is critical because patients with pleural SS can be susceptible to chemotherapy, and accordingly are treated, while patients with sarcomatoid MM are resistant to chemotherapy and accordingly are not treated.