Glomerular injury in uninephrectomized spontaneously hypertensive rats. A consequence of glomerular capillary hypertension.

Micropuncture and/or morphologic studies were performed in intact Wistar-Kyoto rats (WKY) (group 0), intact spontaneously hypertensive rats (SHR) (groups 1 and 5), uninephrectomized (UNX) WKY (groups 2 and 6), and UNX SHR (groups 3 and 4, 7 and 8). UNX was performed when rats were 5 wk of age. Groups 0-4 were observed for 34 wk after which whole kidney clearance and morphologic studies were performed. Groups 5-8 underwent micropuncture study at 10 wk of age. Groups 4 and 8 were fed a diet containing 6% protein. All other rats ingested standard laboratory diet. 5 wk after UNX, normotensive group 6 had higher single nephron glomerular filtration rate (SNGFR) and initial glomerular plasma flow rate (QA) than intact, hypertensive group 5. Glomerular transcapillary hydraulic pressure difference (delta P) was similar in these two groups. Hypertensive group 7 exhibited less elevation in SNGFR and QA than group 6, but delta P was significantly increased. The presence of glomerular capillary hypertension in UNX SHR at 10 wk was associated with the development of significant proteinuria and an increased incidence of mesangial expansion and glomerular sclerosis at 7 mo (group 3) as compared with groups 0, 1, and 2. Protein restriction prevented the development of increased delta P in UNX SHR (group 8) and also conferred long-term protection from increased urinary protein excretion and glomerular injury (group 4). These studies suggest that glomerular capillary hypertension predisposes to glomerular injury in this model of hypertension with reduced renal mass.

Membranes nephropathy associated with renal cell carcinoma. Evidence against a role of renal tubular or tumor antibodies in pathogenesis.

A patient with the nephrotic syndrome due to membranous nephropathy was found to have renal cell carcinoma. Since membranous nephropathy in patients with malignancies has been attributed to a tumor antigen-antibody complex form of glomerulonephritis, an attempt was made to implicate tumor antigens and/or renal tubular epithelial antigens in the pathogenesis of membranous nephropathy in our patient with renal cell carcinoma. Antibodies directed against tumor antigens and renal tubular antigens and renal tubular eipthelial antigens were sought in his serum and in eluates of his glomeruli; no such antibodies were found. The concurrence of the two renal lesions may have been fortuitous in this patient. However, their association temporally suggests that they were related, and our immunologic studies demonstrate that tumor antigen-antibody complexes are not invariably involved in the pathogenesis of malignancy-associated membranous nephropathy.

Breast sarcoma with giant cells and osteoid. A case report and review of the literature.

Breast sarcomas with giant cells and osteoid are rare and usually fatal. They should be distinguished from carcinomas with sarcomatous metaplasia. Our case is presented together with eight similar ones reported in the English literature. Their clinical, radiologic, gross, and histologic characteristics are analyzed. Most patients died within 1 1/2 years of diagnosis, survival apparently being related to the size of the tumor. Diagnosis is delayed because the tumor can be confused clinically and radiologically with a large fibroadenoma. Awareness of this problem, fine-needle aspiration, and computerized tomography may lead to earlier diagnosis and, consequently, improved survival. In our case, immunohistochemical studies supported the notion that the lesion was a primary sarcoma, rather than a carcinoma with sarcomatous metaplasia.

Carcinoma of the prostate with atypical immunohistological features. Clinical and histologic correlates.

In seven patients with undifferentiated carcinoma of the prostate, the immunohistochemical stain for prostate-specific antigen was negative. The stain for prostatic acid phosphatase done on the same tissue samples was diffusely positive in three, focally positive in three, and negative in one. Only the three with diffusely positive immunostaining had elevated serum acid phosphatase levels, although five had evidence of metastatic disease. All seven neoplasms were histologically similar, being composed of large cells with large nuclei, a moderate amount of cytoplasm, and indistinct cell borders. All tumors grew as broad sheets within the prostatic stroma as well as in the prostatic urethra; in six cases. Thus, prostatic carcinoma with this histologic pattern frequently loses prostate-specific antigen immunoreactivity. Awareness of this occurrence should prevent a misdiagnosis of urothelial carcinoma in such cases. The prostatic origin of these neoplasms can usually be verified by prostatic acid phosphatase immunostaining, which proves to be more sensitive in this particular setting.

Primary localized amyloidosis of the nose and paranasal sinuses. A case report with immunohistochemical observations and a review of the literature.

Primary localized amyloidosis of the nose and nasopharynx is a rare disease. We present a case and review seven additional cases from the English literature. The ages of the patients ranged from 8 to 86 years; there was no sex predominance. Symptoms were nasal obstruction, epistaxis, and impaired hearing. Physical examination revealed a nasal mass or glue ears. The lesions were composed of amyloid and chronic inflammatory cells, mainly plasma cells. Ours is the first case of nasal amyloidosis in which the type of amyloid was determined immunohistochemically to be amyloid light chain (AL) lambda. The main treatment was surgical. Recurrences developed. Determination of the biochemical nature of this amyloid clarified its pathogenesis and may influence treatment. Amyloidosis should be considered in the differential diagnosis of nasal obstruction, epistaxis, and glue ears, even in the pediatric age group.

Congenital cystic adenomatoid malformation of the lung in adults.

Congenital cystic adenomatoid malformation of the lung presents mainly in neonates, is rare in children beyond infancy, and has not been reported in adults. Two adult males (aged 24 and 35) had congenital cystic adenomatoid malformation of the right and left lower lobes respectively. A third case, that of a 7-year-old girl, provided the link between the typical neonatal and these adult cases. All three lesions consisted of single or multiple macroscopic cysts, as well as a network of interconnecting spaces (the adenomatoid component). The lining varied from pseudostratified columnar ciliated, to simple mucinous and cuboidal epithelium. Abundant smooth muscle was present in two cases. Cartilage was absent in all three cases. The absence of inflammation is typical of the lesion in neonates. By contrast, all three of our patients had clinical and pathologic evidence of chronic inflammation. We postulate that congenital cystic adenomatoid malformation, when confined to a lobe or segment, may be clinically silent in infancy and may present as pneumonia associated with a cystic lesion on chest x-ray in childhood or later life.

Pathology of dysproteinemia: light chain amyloidosis, non-amyloid immunoglobulin deposition disease, cryoglobulinemia syndromes, and macroglobulinemia of Waldenström.

This review has dealt with four syndromes associated with dysproteinemia, and has emphasized studies of the tissue deposits and forms of tissue injury which occur in such patients. However, similar tissue deposits and tissue damage occasionally occur in the absence of a serum or urine paraprotein, in which case other clinical data are necessary to suggest the need for examination of tissue for Ig heavy and light chain determinants in order to provide a correct diagnosis of dysproteinemia. In such cases, one may speculate that there is a low rate of paraprotein production and secretion, in addition to tissue tropism. Some paraproteins are antibodies, in which case they may circulate and/or deposit as immune complexes, or bind to tissue antigens with immune complex formation in situ. Some paraproteins are also cryoproteins, and clues to this property can also be found in the tissue, particularly at the ultrastructural level. Thus, a wide spectrum of clinical manifestations of a B cell proliferative disorder may be associated with any of a variety of circulating paraproteins and a variety of forms of tissue deposit and injury. Consequently, the best understanding of an individual patient requires correlation of the clinical features of the disorder, the immunochemical characterization of the circulating and excreted paraproteins, and an immunohistochemical analysis of the tissue deposits and associated morphologic abnormalities. This should be correlated with histologic and immunohistologic assessment of bone marrow, looking for overt B cell neoplasia, the more difficult to define "lymphoproliferative disorders," or alterations in kappa to lambda plasma cell ratios which may correlate with the deposited material. Studies of the Ig synthesized by cultured bone marrow plasma cells, and biochemical analyses of the deposited material, have demonstrated structural abnormalities of paraproteins which may be responsible for their tissue deposition.

Relationship of tissue deposits of cryoglobulin to clinical features of mixed cryoglobulinemia.

Two patients with type 2 mixed cryoglobulinemia had tissue deposits of serum cryoproteins. Patient 1, a 72-year-old man, had purpura and glomerulonephritis. The serum cryoglobulin consisted of monoclonal IgM kappa and polyclonal IgG. Renal biopsy revealed diffuse proliferative glomerulonephritis with abundant IgG, IgM, kappa light chain, and complement in glomerular capillary walls. These immunoglobulins, but no complement, were also present in histologically normal cutaneous blood vessels. Ultrastructurally, cutaneous vascular deposits were identical to the renal deposits and to the crystalline mixed IgM-IgG serum cryoprecipitates and renal deposits previously described. Patient 2 was a 68-year-old man with sensorimotor peripheral polyneuropathy and purpura. His serum cryoglobulin consisted of monoclonal IgA lambda and polyclonal IgG. Sural nerve and skin biopsies revealed vasculitis involving small arteries and arterioles. Immunoglobulin A and complement were present in perineurial arteriolar walls of the sural nerve. Cryoprecipitates in both cases had strong rheumatoid factor activity. These findings support the view that in type 2 cryoglobulinemia tissue deposits consist of cryoprotein immune complexes. The presence of these deposits in histologically normal blood vessels in patient 1 suggests that deposition of cryoproteins precedes and may initiate tissue damage.

Glomerulonephritis in congenital cytomegalic inclusion disease.

Except for renal transplant recipients, glomerulonephritis has only very rarely been associated with renal cytomegalovirus (CMV) infection. The kidneys of five infants with congenital cytomegalic inclusion disease, including renal infection, were examined at autopsy. Two of the infants had glomerulonephritis. The younger, a 4-month-old female, had diffuse proliferative and necrotizing glomerulonephritis; virus was present in nuclei and cytoplasm of glomerular endothelial cells and, possibly, in leukocytes as well. There were no electron-dense deposits. The other infant, a 5-month-old male, had diffuse mesangial and focal segmental proliferative and sclerosing glomerulonephritis; electron-dense mesangial deposits were seen ultrastructurally. Three additional infants (a newborn male, a 2-day-old male, a 6-week-old female), all with CMV in tubules and one with a single glomerular inclusion, had only rare glomerular abnormalities, i.e., mesangial proliferation in less than 10 per cent of glomeruli (one infant) and segmental sclerosis in less than 1 per cent of glomeruli (all three infants). Thus, congenital renal CMV infection was associated with proliferative glomerulonephritis in the two infants who survived the longest. The three with shorter survival times had only minor glomerular alterations.

Inflammatory abdominal aortic aneurysm: report of six cases.

Six cases of inflammatory aneurysm of the abdominal aorta are described. All patients were male, aged 59 to 80 years, and five had symptomatic atherosclerotic cerebrovascular or cardiovascular disease. In three the diagnosis of inflammatory aneurysm was suggested preoperatively on the basis of computed tomographic or ultrasonographic scanning. On gross examination the aneurysm wall was about 1 cm thick and included an inner narrow layer of atherosclerotic plaque, which was contiguous with the outer thick fibroinflammatory component. Microscopically, this component consisted of fibroblasts and collagen, which entrapped fat, nerves, and lymph nodes and was infiltrated by lymphocytes and plasma cells. Plasma cells, lymphocytes, and fibroblasts predominated in four patients, while two showed abundant dense collagen with fewer inflammatory cells and fibroblasts. There was associated vasculitis, predominantly phlebitis, in three. Inflammatory aneurysms represent a distinct group of abdominal aortic aneurysms.

Wilms' tumor: a search for the critical lesion.

A Wilms' tumor from a 12-month-old boy showed epithelial and mainly rhabdomyoblastic differentiation. In addition, the kidney contained foci of nephroblastomatosis, a lesion predisposing to the development of nephric tumors. Flow cytometry indicated that the tumor DNA content was in the diploid range with an increased S-phase. Chromosome studies of the cultured tumor cells showed a dominant pattern of 49,XY, +8,9qh+, +12, +12,18q+, without obvious deletion of 11p. A few cells showed additional losses, deletions, or structural rearrangements superimposed on the basic pattern, but no normal metaphases were observed. The DNA from the tumor was probed for several loci on 11p because variations of 11p (deletion or translocation) have been reported in roughly one third of Wilms' tumors, and the critical gene in Wilms' has been localized to 11p13. In this case, 11p genes maintained heterozygosity or showed no detectable alteration in gene dosage when compared with peripheral-blood DNA. Therefore, despite histologic indication of an underlying constitutional defect, no genomic lesion of 11p was identified.

Testicular stromal tumor with myofilaments: ultrastructural comparison with normal gonadal stroma.

The ultrastructural features of two testicular stromal tumors were compared with those of normal gonadal stroma. The two patients with tumor were 28 and 48 years old and had no endocrine abnormalities. No metastases or recurrences occurred after 32 and 12 months of follow-up, respectively. The tumors were composed of bundles of oval to spindle-shaped cells. Ultrastructurally, intracytoplasmic myofilaments were characteristic of the tumor cells, which resembled the contractile peritubular and interfollicular cells of normal testis and ovary. In normal testicular tissue, an intertubular mesenchymal cell may differentiate into a peritubular contractile cell or into an interstitial (Leydig) cell. Therefore, testicular stromal tumors with myofilaments may originate from an intertubular mesenchymal cell that is capable of differentiating into a cell with contractile elements.

Immunophenotypic evaluation of the bone marrow in non-Hodgkin's lymphoma.

Immunophenotypic evaluations of the bone marrow (BM) are reported on 69 aspirates from 58 patients who had non-Hodgkin's lymphoma or chronic lymphocytic leukemia involving the BM. Using flow cytometry and immunofluorescence microscopy on density gradient isolated BM mononuclear cells, the neoplasm could be identified and characterized in 59 aspirates (86%) from 49 patients (84%). Using International Working Formulation guidelines the neoplasms were classified on the basis of prior or subsequent histopathology of lymph node, spleen, skin, or other soft tissue site, or by evaluation of peripheral blood in chronic lymphocytic leukemia. In nine cases the lymphoma could not be completely classified according to International Working Formulation guidelines because only BM was available for evaluation. The neoplasm in the BM was identified and characterized immunophenotypically in all 29 cases of chronic lymphocytic leukemia/well-differentiated lymphocytic lymphoma (WDLL) (100%), in 11 of 12 cases of low-grade lymphoma other than WDLL (92%), in 11 of 15 cases of intermediate-grade lymphoma (73%), and in two of four cases of high-grade lymphoma (50%). Six of the nine cases not classified by International Working Formulation guidelines could be characterized immunophenotypically. In 10 cases immunophenotypic studies revealed negative findings, although the concurrent core biopsy specimens were positive. In two cases immunophenotypic studies with positive findings accompanied a negative core biopsy specimen. A panel of immunohistochemical reagents reactive with fixative/paraffin-resistant antigens was used for a retrospective evaluation of the 69 core biopsy specimens. When compared with the immunophenotypic data obtained from the marrow aspirates these results proved to be only moderately reliable in B-lineage neoplasms and unreliable in T-cell neoplasms. Thus, immunophenotyping of aspirated marrow by flow cytometry was found to be the most reliable method for determining the antigenic profiles of BM-based lymphomas.

A retrospective analysis of breast cancer based on outcome differences.

We reviewed tumors from two groups of patients with breast cancer, distinguished by differences in outcome. One group (85 cases) survived more than 8.5 years without tumor recurrence; the other 85 cases had recurrent disease within 2 years. Histologic and immunocytochemical studies on all cases were performed without patient identifiers and prior to review of clinical prognostic factors. As expected, lymph node and estrogen receptor status differed substantially between the groups, but menopausal status and family history for breast cancer did not. We noted that 27% of node-negative patients died within 5 years, and nine patients with four or more tumor-containing nodes were symptom-free for over 8.5 years. Histologic grade (degree of tubule formation) and nuclear grade (including mitotic rate) differed significantly between the groups, as did vascular invasion, including both lymphatics and blood vessels. Prognostic value attached to tumor border only when fat was invaded without fibroblastic or inflammatory response (P = .012). Subgrouping cases of infiltrating ductal carcinoma (not otherwise specified) was prognostically informative in the B subgroup, 69% of whom were in the rapidly recurrent tumor group. Immunocytochemical staining for c-erbB-2 was positive in 19.3% of cases, but was equally distributed between the two outcome groups. We conclude that traditional histologic parameters are highly informative, and that c-erbB-2 studies do not increase the value of histologic diagnosis.

Calcium carbonate exacerbates glomerular capillary hypertension and injury in rats with desoxycorticosterone-salt hypertension.

To examine the effects of dietary calcium supplementation on systemic and renal hemodynamics and glomerular injury in experimental hypertension, rats with desoxycorticosterone-salt hypertension were fed either standard chow, containing 1% calcium by weight, or chow supplemented with calcium carbonate to achieve a calcium content of 2% by weight. Ingestion of calcium carbonate failed to reduce systemic blood pressure, but was associated with increased proteinuria and morphologic evidence of glomerular injury. Micropuncture studies revealed that afferent arteriolar resistance was reduced and glomerular capillary pressure further increased in the high calcium group. Thus, calcium carbonate, in moderate amounts, not only failed to ameliorate systemic hypertension but, paradoxically, worsened intrarenal hypertension and injury in rats with mineralocorticoid-induced hypertension.

Acquired cystic disease of kidney in chronic dialysis patients.

Eight cases of acquired cystic disease of the kidney (ACDK) associated with chronic renal failure and hemodialysis are described. No patient had a family history or clinical evidence of congenital adult polycystic kidney disease (CAPKD). Glomerulonephritis was the cause of renal failure in 6, and pyelonephritis in 2. Massive renal and perirenal hemorrhage necessitated 3 nephrectomies in 2 patients. Single kidney weights did not exceed 280 Gm., a major feature in the distinction of ACDK from CAPKD. Morphologically, in addition to the usual stigmata of end-stage kidneys, 40 to 80 per cent of the renal parenchyma was replaced by small cysts. Continuity of cysts with tubules was established by nephron dissection.

Pseudomonas cepacia endocarditis and ecthyma gangrenosum.

A case of right-sided Pseudomonas cepacia endocarditis in a heroin addict is presented in which septic cutaneous vasculitis (ecthyma gangrenosum) is a prominent feature. Ecthyma gangrenosum, most commonly associated with sepsis due to P aeruginosa, has not been previously described with P cepacia septicemia.

Intrarenal vascular sclerosis in IgA nephropathy.

In this analysis of 43 patients with IgA nephropathy, renal morphology was correlated with clinical data. Gross hematuria and mild proteinuria were typical among younger patients. Among older individuals the clinical spectrum was wider. A comparison with data previously obtained from the normal population indicated that disease-related glomerular sclerosis was present in 1/3 of initial biopsy specimens. The prevalent pattern of glomerular sclerosis was that of global tuft collapse, the type of sclerosis known to result from ischemia. Intrarenal vascular sclerosis was present in 1/3 of initial biopsies. Follow-up specimens from 6 patients showed progression of glomerular sclerosis, vascular sclerosis or both. Hypertension occurred in over 1/4 of patients. It is proposed that progressive renal damage in IgA nephropathy may not be solely immunologically mediated. Glomerular sclerosis may also be mediated by vascular sclerosis, or alterations in intrarenal hemodynamics in glomerulonephritis may have a direct damaging effect on both the glomerulus and the intrarenal vasculature.

Role of intrarenal vascular sclerosis in progression of poststreptococcal glomerulonephritis.

A comparison has been made of the percentage of sclerotic glomeruli found in normal subjects and in 31 patients 6 months to 15 years after an episode of acute poststreptococcal glomerulonephritis (PSGN). The findings establish that a greater than expected incidence of glomerular sclerosis occurs in the course of PSGN. The pattern of glomerular sclerosis frequently was that of contracted collapsed tufts, one known to result from ischemia. In the majority of specimens with significant glomerular sclerosis, there was co-existent vascular sclerosis (arterioles and/or prearterioles), and the incidence of both glomerular and vascular sclerosis increased with time from onset of PSGN. Intrarenal vascular sclerosis may thus be of major importance in the genesis and progression of glomerular sclerosis in PSGN.

Clinical implications of the rare thyroid carcinoma which is indistinguishable from a follicular adenoma.

The inadequacy of the standard pathologic criteria for identifying certain well-differentiated thyroid follicular carcinomas from follicular adenomas in rare instances is illustrated by four cases. The excised thyroid nodule in these patients appeared to be adenoma, but subsequent local spread in the neck or distant metastases disclosed the actual malignant nature of the lesions. This observation is not intended as a basis for more extensive operations for adenoma, but rather as an indication for close, long-term observation. Postoperative, lifelong suppressive therapy with thyroid hormone is suggested for all patients with a diagnosis of follicular adenoma.