Marcel W. Seiler

Ultrastructural markers of colonic adenocarcinoma

A mixed population of 96 adenocarcinomas was examined by electron microscopy to establish the presence of organ specific features. This resulted in the identification of fine structural characteristics, occurring consistently in colorectal adenocarcinomas but not in other epithelial tumors. The colorectal “ultrastructural profile” consists of microvilli with dense cores of microfilaments extending as long rootlets into a clear zone of apical cytoplasm, apical electron dense bodies, and abundant glycocalyceal bodies. Of these features, the long rootlets constitute the best morphologic marker for large intestinal type adenocarcinoma. Using these characteristics in another series of 58 adenocarcinomas studied in a double‐blind manner, it was possible to distinguish colorectal adenocarcinomas from other carcinomas on ultrastructural grounds alone.

Pulmonary hamartoma. An ultrastructural study

Three so‐called pulmonary hamartomas were studied by electron microscopy. Histologically, the hamartomas included one case with mainly mature cartilage (chondroma), one with loose myxoid fibrous tissue and rare areas of mature cartilage, and one with only loose myxoid fibrous tissue. Ultrastructurally, a common feature in all three cases was the presence of stellate, undifferentiated mesenchymal cells. These cells were sparse in the chondroma, and abundant in the other two cases. Areas of transition between undifferentiated mesenchyme and cartilage were present in two cases (the condroma and the myxoid fibrous tumor with areas of mature cartilage). Unusual stellate smooth muscle cells were present in areas of loose myxoid tissue. The epithelial components revealed continuity and morphologic identity to terminal bronchiolar and alveolar epithelium. A distinct basement membrane was always present. These observations support the concept that pulmonary hamartomas represent a histologic spectrum of benign mesenchymal neoplasms, which originate in peribronchial connective tissue and incorporate respiratory epithelium as they expand.

Sarcomatoid Renal Cell Carcinoma Metastatic to the Heart: Report of a Case

An unusual case of metastatic sarcomatoid renal cell carcinoma is presented. Fifteen months after nephrectomy for a typical clear cell carcinoma, a 63-year-old man presented with bilateral pleural effusions, cardiomegaly, and tamponade. A pericardial biopsy showed an anaplastic spindle cell tumor that was strongly keratin positive and showed desmosomes ultrastructurally. The patient died shortly thereafter, and the autopsy revealed massive tumor infiltration of the heart, pulmonary and adrenal metastases, and tumor nodules at the incision site of his nephrectomy. The differential diagnosis of sarcomatoid renal cell carcinoma is discussed.

Extratubular Tamm-Horsfall protein deposits induced by ureteral obstruction in mice

The effects of unilateral ureteral obstruction were studied in mice. Obstruction for 24 hr led to the formation of extratubular Tamm-Horsfall protein (TH) aggregates within the renal interstitium and at the base of distal convoluted tubular (DCT) cells. These DCT deposits were shown by ultrastructural analysis to be entirely extracellular. They had the fibrillar substructure characteristic of TH and had not been seen after urinary obstruction in other species. As a consequence of retrograde flow of urine to glomeruli, obstruction also caused TH aggregates to form within Bowmans spaces. These glomerular casts of TH were detected throughout the 3-week period of study after the release of unilateral obstruction. High serum titers of IgG antibodies to TH developed in mice intradermally immunized with TH but were not observed after obstruction alone. Circulating anti-TH antibodies combined with TH present on the basal surfaces of the thick ascending limb of the loop of Henle cells and DCT cells to form immune complexes in situ. Interstitial inflammation in the areas surrounding subepithelial tubular immune deposits was not present in the kidneys of immunized mice and was not selectively induced by temporary obstruction. However, foci of inflammation were seen in all obstructed kidneys. At later times, inflammatory foci in previously obstructed kidneys were associated with progressive scarring, primarily in polar regions. The location and severity of these changes within kidneys produced by obstruction in immunized mice did not differ from those in unimmunized mice. The titers of anti-TH antibodies in immunized mice were not enhanced or depressed as a consequence of unilateral ureteral obstruction. These studies demonstrate that complete obstruction of urinary flow in the mouse for periods as short as 24 hr may lead to progressive segmental renal scarring. These studies further indicate that increasing the quantities of extracellular TH by obstruction does not facilitate inflammatory responses to TH immune complexes formed in situ. While exposure of renal tissue to highly toxic components of extravasated urine may play a crucial role in inflammatory responses, autoimmunity to TH was not implicated as a contributing factor by the present studies in mice.

Aorticopulmonary Paraganglioma (Aortic Body Tumor): Report of a Case

A case of aorticopulmonary paraganglioma in a 57-year-old man is described. The tumor comprised nests of uniform cells in a fibrovascular stroma. Electron microscopy revealed abundant neurosecretory granules, and S-100 protein staining demonstrated scattered sustentacular cells at the periphery of typical zellballen. The findings in this case correlated with those of studies on the prognosis for extraadrenal paragangliomas.

Autoimmunity to Tamm-Horsfall Protein

Although interstitial inflammation and fibrosis, and tubular damage are prominent pathologic features in a variety of renal diseases, the pathogenesis of these lesions has received much less attention than have mechanisms of glomerular injury. Recently, clinical and experimental studies have shown that, in addition to well-established roles of immunologic mechanisms in glomerulonephritis, such immune mechanisms can cause tubulointerstitial nephritis also. Primary antibody-mediated tubular and interstitial lesions may be caused by either antibodies to tubular basement membranes (TBM) or by immune complexes. Anti-TBM-mediated nephritis is characterized by a smooth linear pattern of immunoglobulin fixed along the TBM, and the pathogenesis of these lesions has been discussed in detail (McCluskey and Colvin, 1978). In this discussion, features of tubulointerstitial nephritis mediated by immune complexes and having a granular staining pattern will be presented with emphasis on the pathogenesis of renal lesions produced by antibodies to Tamm-Horsfall protein (TH), a urinary glycoprotein of renal origin.