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Open biopsy of the corpus cavernosum was performed in 13 nondiabetic patients with erectile dysfunction. The history and physical examination, sleep rigidity and tumescence monitoring, hormonal assays, duplex ultrasonography with papaverine, and cavernosometry and cavernosography, formed the basis of categorizing each patient into 1 of 5 etiological groups. These groups included neurogenic, moderate arterial, severe arterial, venous and fibrotic causes for organic erectile dysfunction. The cavernous smooth muscle and endothelium in each patient appeared to be normal on light and electron microscopy. We conclude that cavernous biopsy is of limited value to determine therapeutic options in patients with erectile dysfunction.

Interpretation of breast biopsies has assumed a large and important component of the surgical pathologist's practice. Currently, about 10% of women will develop breast carcinoma during their lifetime. This high incidence, coupled with increased public awareness of breast disease, greater use of screening mammography to detect early carcinomas, development of multiple therapeutic options (the latter often influenced by the pathology of the tumor), and a harsh medicolegal climate have placed greater demands on surgical pathologists for accurate interpretation of breast tissues. The focus of this report is to define the clinicopathologic features of five benign breast lesions that mimic malignant breast disease, and thus pose important diagnostic considerations to surgical pathologists.

We report a unique carcinosarcoma of the ovary having an organoid growth pattern that resembled immature teratoma. The tumor contained both adenocarcinoma and squamous carcinoma (focally sebaceous) admixed with chondrosarcoma, rhabdomyosarcoma, and malignant neuroectodermal components. The neuroectodermal components were prominent, resembling ependymoblastoma, medulloepithelioma, ganglioneuroblastoma, glioblastoma multiforme, and pigmented neuroectodermal tumor. Immunohistochemical studies dramatically revealed carcinoma and rhabdomyosarcoma admixed with malignant neuroectodermal tumor. Implants of papillary serous carcinoma (with psammoma bodies) were present in the opposite ovary, uterine serosa, omentum, and appendiceal serosa. Although a variant not previously described in the ovary, this ovarian carcinosarcoma closely resembled nasopharyngeal tumors described as teratoid carcinosarcoma or terato-carcinosarcoma.

Two patients developed nodular, well-circumscribed tumors of the breast, discovered by mammography. They were fibroadenoma-like by gross examination and biphasic by light microscopy, containing both tubular glands and spindled myoid cells. Immunocytochemical studies revealed cytokeratin and S-100 immunoreactivity in both the spindled myoid cells and in the tubuloglandular cells (S-100 was focal in the latter). In addition, the spindled myoid cells were immunoreactive for vimentin but negative for desmin. Ultrastructural studies showed the tubular glands to be composed of luminal epithelial cells focally surrounded by myoepithelial cells, but the stroma contained spindled myoepithelial cells admixed with occasional fibroblasts. The diagnostic term, "adenomyoepithelioma," is appropriate for biphasic tumors having both glandular and myoepitheliomatous differentiation. Although additional experience is necessary to be conclusive regarding the biologic behavior of these unusual lesions, the authors believe the adenomyoepitheliomas described here are benign. They were well circumscribed without invasion of adjacent breast, contained neither mitotic figures nor cytologic atypia, and have not recurred or metastasized (6 and 10 months after removal).

We report two cases of unexplained, isolated, persistently increased aspartate aminotransferase activity in serum. In the first patient, this lasted for 10 years and prompted multiple hospitalizations and medical/surgical consultations. For patient two, the abnormal enzyme activity resulted in hospitalization for further evaluation of possible heart disease. In spite of extensive investigation to determine the possible reason for the abnormality, no clear clinical cause was ever discovered in either patient. Electrophoretic and immunologic evidence indicates that the enzyme was complexed to IgG in the serum of both individuals. Recognition that this complex is probably benign may obviate other patients having to undergo unnecessary hospitalization, anxiety, and expense.

Two cases of an aggressive cutaneous carcinoma showed both squamous and adenomatous differentiation. These neoplasms invaded subcutaneous structures with a sclerosing pattern, making surgical resection difficult. Unlike the usual squamous carcinoma, glands and epithelial mucin (sialomucin) were produced. This mucin stained with mucicarmine and was sensitive to sialidase and resistant to hyaluronidase digestion. No mucin with similar histochemical properties was found in a study of 50 consecutive cutaneous squamous carcinomas and 50 consecutive basal cell epitheliomas from our files. Literature reports of histologically similar cutaneous carcinomas together with our experience with these two cases suggest aggressive behavior for this category of neoplasm.

A unique case of carcinosarcoma of the colon is reported. The tumor invaded the bowel wall deeply, metastasized widely, resisted multi-agent chemotherapy, and caused the patient's death 4 years later. The tumor was composed of adenosquamous carcinoma admixed with sarcoma showing osseous, cartilaginous, and nonspecific spindle-cell differentiation. Although carcinoembryonic antigen appeared limited to carcinoma cells, cytokeratin immunoreactivity was observed in both carcinoma and sarcoma cells. Like carcinosarcomas at other body sites, the finding of cytokeratin in sarcoma cells supports partial epithelial differentiation in this component, likely retained from carcinoma precursor cells.

Giant cell tumors of synovium (pigmented villonodular synovitis) involving the vertebral column recently have been seen in two women: the third and fourth cases to be reported in the English-language literature. Unlike the previously reported cases, both these tumors grew outside the dura and produced symptoms of spinal cord compression. The first case involved lumbar vertebrae 5 and 6; the second, lumbar vertebrae 2 and 3. Even though initial resection of both tumors was incomplete, the patients improved postoperatively. One tumor was known to be unresectable at the time of surgery. In the other patient, a recurrence of symptoms required second and third resections 4 and 8 months after the first, respectively. Although synovial giant cell tumors rarely metastasize, the rate of local recurrence is high, especially if excision is incomplete. For this reason, close follow-up of patients with lesions in the spinal column is indicated. Increased physician awareness that synovial giant cell tumors can occur in the spine will help to ensure that these tumors are not misdiagnosed in this location.

Recent development of an antibody to the M subunit of lactic dehydrogenase (LDH) allows the rapid isolation and measurement of LDH-1 levels. I and my colleagues studied 101 consecutive patients admitted to the hospital for possible acute myocardial infarct (AMI). The LDH-1 level was 100 IU/L or more, and the ratio of LDH-1 to total LDH (LDH-1/LDH-T ratio) was 0.40 or higher, during the course of illness in 93% of the patients with AMI. The specificity was 95% and the positive predictive value, 86%. These two criteria were met eight to 24 hours after the appearance of symptoms, and often persisted seven to 14 days. Measurement of LDH-1 level and LDH-1/LDH-T ratio is a useful adjunct in the laboratory diagnosis of AMI.

Peptic ulceration is a known complication of hepatic arterial chemotherapy for metastatic disease. We report a case of peptic ulceration associated with marked epithelial atypia initially interpreted as carcinoma, probably metastatic in nature. Subsequent partial gastric resection proved the lesion benign. Examination of other gastric biopsies from ulcerated and nonulcerated mucosa from similarly treated patients has revealed similar marked atypical changes. The etiology of the epithelial atypia and ulceration remains unanswered, but is probably related to locally enhanced chemotherapeutic cytotoxicity or ischemia. Care should be taken not to interpret the marked epithelial atypia as carcinoma in this clinical setting.

Two unusual cases of colonic ganglioneuromatosis are described. One case was associated with multiple adenomatous polyps in a 74-year-old man and the second case was associated with juvenile polyps in a 16-year-old boy. To our knowledge this is the first report of colonic mucosal ganglioneuromatosis associated with multiple adenomatous polyps and the second report associated with multiple juvenile polyps. In the first case the ganglioneuromatosis was found in colonic mucosa without adenomatous changes, while in the second case ganglioneuromatosis was found both within normal mucosa and within juvenile polyps. The relationship between mucosal ganglioneuromatosis and multiple colonic polyps remains unclear. Neither patient has yet developed features to suggest either multiple endocrine neoplasia type 2b or von Recklinghausen's disease.

Two patients developed extremely bizarre (pseudomalignant) granulation-tissue reactions in the larynx and facial sinuses, following radiation therapy for carcinoma. Containing pleomorphic spindle cells and numerous (sometimes atypical) mitotic figures, both tumefactive lesions simulated high grade malignancies. While the pleomorphic cells contained vimentin immunoreactivity, they were nonreactive for low or high molecular weight keratin. Flowcytometric study of paraffin-embedded tissues revealed DNA indexes of 0.75 and 1.0. Neither recurred locally nor spread distantly after therapy. Their granulation-tissue growth pattern, and the presence of stromal and endothelial cells showing similar degrees of cytologic atypia were central to their recognition as benign. These findings show that severely atypical, sometimes aneuploid, granulation-tissue reactions can occur following radiation exposure. Care should be taken not to misinterpret these lesions as malignant.

A patient is described with chronic colitis, watery diarrhea, and colonic mucosal subepithelial collagen deposition that resolved while being treated with sulfasalazine. The clinicopathologic features were consistent with collagenous colitis. Theoretically, the thickened collagen layer impairs water and electrolyte absorption, producing watery diarrhea. Such increased collagen is rarely observed in other inflammatory colon diseases and may represent a distinct morphologic reaction to various, yet undefined, injuries. Although the clinical course is benign, appropriate therapy for the debilitating symptoms is poorly understood. This report suggests that sulfasalazine may be helpful in some cases.

We report a case of neuroid giant congenital melanocytic nevus (GCMN) in which a malignant schwannomalike tumor developed. Literature review reveals that neurosarcomatous differentiation occurs among malignant tumors arising in GCMNs, apparently with greater incidence in those GCMNs showing benign neuroid differentiation. Although the differences between neuroid melanocytes and Schwann's cells may be more conceptual than real, we believe that the current tumor arising within a melanocytic nevus is likely of neuroid melanocytic origin and best designated as neurosarcomatous malignant melanoma.

A bonded reversed phase, high pressure liquid chromatography (HPLC) method for serum quinidine and its major metabolite in serum, (3S)-3-hydroxyquinidine, is presented. The method employs toluene, rather than benzene for extraction of 100 microliter of serum, can utilize either absorbance or fluorescence detectors, and utilizes a column and equipment which is also suitable for theophylline analyses. Quinidine values in sera by the present method correlated well with fluorometric non-chromatographic methods using ethylene chloride (r = 0.932) or benzene-sulfuric acid (r = 0.950) for extraction of the quinidine. The comparison data suggest a therapeutic range for quinidine of 1.3--5.0 mg/liter when measured by HPLC. In over one year of routine use in a clinical chemistry laboratory, the method has proven to be rapid and precise with interassay coefficients of variation of 2.5--5.5%. No interferences with the HPLC method have yet been identified.

Reported are the pathologic features of atypical cysts and/or renal cell carcinomas found in the kidneys of four patients having either tuberous sclerosis or Hippel-Lindau disease. In addition, cellular DNA contents of the cells lining the atypical cysts and comprising the carcinomas were quantitated using both static and flow cytometric techniques. These studies showed that cysts lined by atypical epithelial cells are frequently present in renal parenchyma adjacent to the renal carcinomas, and that the cytologic features of atypical cells lining the cysts were essentially the same as the cytologic features found in the adjacent well-differentiated, renal cell carcinomas. DNA quantitative studies revealed that both the renal cell carcinomas and the atypical cyst lining cells had the same DNA indices and were essentially DNA euploid. In this patient group these findings are consistent with the hypothesis that the atypical cyst lining cells evolve into the renal cell carcinomas; however, they do not prove this proposed but likely sequence.

A serial radiographic-pathologic correlation based on specimen radiography was performed on 27 consecutive, clinically occult, noncalcified breast cancers to determine the frequency of and correlation between appearances at mammography, pathologic diagnoses, and the features of the histologic margins. Twenty (74%) of the lesions were infiltrating ductal cancers, five (19%) were intraductal cancers, and two (7%) were medullary cancers. Forty-one percent of these malignancies contained microscopic calcifications. Lesions demonstrated at mammography in these 27 cases consisted of a well-defined round mass (n = 1); well-defined lobulated masses (n = 2); indistinct round, oval, or lobulated masses (n = 7); irregular or mixed lesions (n = 7); spiculated masses (n = 9); and architectural distortion (n = 1). Histologic margins of infiltrating and intraductal cancers, created by several types of tumor-fat interfaces and surrounding reactive fibrosis, correlated with these radiographic appearances. Serial specimen radiographic-pathologic correlation can improve our understanding of the appearance of early breast cancer at mammography.

A high-pressure liquid chromatographic method for the routine measurement of serum theophylline that is accurate, specific, and sensitive is presented. It is technically simple, requires only 50 microliter serum, and takes relatively little technician time. Values for theophylline in sera obtained by this method correlate well with those obtained by use of a gas-liquid chromatographic method (r = 0.980) and with values obtained by the commonly used spectrophotometric method (r = 0.939) when the latter is free of interference. The assay has been employed for two years in a routine clinical chemistry laboratory, with interassay coefficients of variation of 2.4-3.2%. Interferences have been identified at an incidence rate of 3.8% of all specimens, and interfering substances include cephazolin, chloramphenicol, sulfamethoxazole, and sulfisoxazole. A calculation technic that allows a reliable and clinically useful estimation of a range of concentrations of theophylline in the serum when these interferences are present is described. In contrast, the incidence of interferences with the spectrophotometric method is 4.9%, and in this method the interferences prevent the analysis of theophylline. Of 33 samples having interferences by use of the spectrophotometric method, the high-pressure liquid chromatographic technic yielded precise values for theophylline in 21 and reliable estimates of ranges of concentrations of theophylline in the remaining 12.

Two patients presented with hypophosphataemic osteomalacia and were subsequently found to have small tumours unusual histopathology and location causing the osteomalacia. Each tumour was found after an intensive search for occult masses. Studies of vitamin D metabolism and renal tubular function before and after surgery yielded further insight into the pathophysiology of oncogenic osteomalacia. These cases demonstrate that microscopic quantities of tumour are capable of causing the syndrome and further illustrate the high index of suspicion often necessary to locate causative tumours in patients with hypophosphataemic osteomalacia.

We investigated the kinetic characteristics of an enzyme immunoassay system (EMIT) for the determination of theophylline. Less than 10% of the glucose-6-phosphate and NAD+ are consumed and the glucose-6-P-dehydrogenase-theophylline complex is essentially saturated with these substrates during the course of the reaction. However, apparently as the result of antibody heterogeneity, the rate does change during the course of the reaction. As a result, the values of the kinetic parameters for the theophylline saturation curve vary with the timing interval chosen for measurement. We show that the values of these parameters govern the application of the available methods of calculating EMIT data, the graphical procedure suggested by the manufacturer, logit-log, log-log, and curve fitting. These studies (1) explain the basis of the graphical procedure and why it does not always provide proper calibration, (2) show that to appropriately understand the application of any of the calculation procedures one should determine the values of the kinetic constants of the theophylline saturation curve in the particular assay conditions, and (3) illustrate simple, practical procedures for determining the values of these constants for any instrument-EMIT assay system. Specific illustrations are shown for the EMIT theophylline system with two kinetic analyzers, the Abbott ABA-100 and Gilford 3500, with which markedly different reaction conditions are used.

The effect of 30% galactose feeding on kidney function and structure was compared to the effect of streptozotocin-induced diabetes in the rat. In the galactose-fed rats there was increased urine volume (500%), creatinine clearance (40%), urinary albumin excretion (100%), urinary N-acetyl glucosaminidase (600%) and relative kidney weight (21%). These changes were similar to that observed in streptozotocin-induced diabetic animals. Galactitol in the kidney cortex of galactose-fed rats was increased 4 times similar to that observed for sorbitol in the streptozotocin-induced diabetic animals. Glycosylated hemoglobins were also increased in both galactose-fed animals and streptozotocin-treated animals. These data suggest that galactose feeding may be a useful model for investigating some aspects of diabetic nephropathy.

After digestion removed the cells from glomeruli of frozen kidney tissue, we employed scanning electron microscopy to examine the acellular glomerular basement membranes (AGBM) from normal kidneys and from kidneys of patients with dense-deposit disease (DDD). The AGBM showed previously unrecognized three-dimensional patterns of pathologic changes. When compared to normal controls, the AGBM in DDD appeared "rigid" and thickened. Other pathologic features included coarsely granular or undulating epimembranous surfaces punctuated by single or clustered crater-like deformities. Although epimembranous crater-like deformities have been observed in other glomerulopathies, the combination of "rigid"-appearing AGBM punctuated by crater-like deformities is thus far unique to DDD.

Five cases of benign lymphoepithelial cysts (BLCs) of the parotid gland are reported, and the histologic, aspiration cytologic, and ultrastructural findings are described in detail. These uncommon parotid lesions contain epithelium-lined cystic spaces encased by abundant lymphoid tissue with germinal centers. The epithelium was "mucoepidermoid" in three of our cases and squamous in two. Familiarity with the morphologic features of BLCs should make it possible to distinguish them from similar-appearing cystic lesions, especially low-grade cystic mucoepidermoid carcinoma and cystic types of benign lymphoepithelial lesion (so-called Mikulicz's disease). These distinctions, however, are difficult on aspiration cytology specimens.

A young Caucasian woman had a large area of blue-gray discoloration on the flank and palpable axillary lymph nodes. The discolored area had enlarged during a recent pregnancy, contained multiple subcutaneous nodules, demonstrated increased cellularity and mitotic activity, and was associated with an axillary lymph node containing black streaks within the capsule. Although the lesion was initially considered to be a metastatic malignant melanoma, re-evaluation showed it to be a benign cellular blue nevus with benign nevus-cell aggregates within a regional lymph node. We report this case to emphasize how cellular blue nevus can simulate malignant melanoma and to increase physician awareness of this benign variant of melanocytic nevus so that inappropriate surgery and chemotherapy can be avoided.

Gastric antral vascular ectasia was endoscopically diagnosed in seven patients. Pathologic characteristics of this entity were defined retrospectively, by studying endoscopic pinch biopsy slides from these seven patients and antrectomy specimens from five patients. A scoring system was developed, and the seven patients were compared prospectively with various control groups. Abnormalities of mucosal vessels (fibrin thrombi and/or ectasia) consistently distinguished patients from control antrectomies, normal biopsies, acute gastritis biopsies and atrophic gastritis biopsies (P = 0.02, all comparisons). Spindle cell proliferation into mucosa also was characteristic of gastric antral vascular ectasia, distinguishing this disease from normals, acute gastritis, and atrophic gastritis (P less than or equal to 0.039, each comparison). The presence of abnormal mucosal vessels (fibrin thrombi and/or ectasia) and spindle cell proliferation was similar in patient antrectomies compared to patient endoscopic biopsies. Therefore, we conclude that endoscopic biopsies can reliably diagnose gastric antral vascular ectasia, a vascular disorder characterized by abnormal mucosal vessels and spindle cell proliferation.

The clinical and pathologic findings of two patients with malignant ectomesenchymomas of soft tissue are reported. Malignant ectomesenchymomas are a composite of ganglion cells or neuroblasts and one or more malignant mesenchymal elements, usually rhabdomyosarcoma. Our first case was composed of ganglioneurosarcoma plus rhabdomyosarcoma, the second composed of neuroblastoma plus rhabdomyosarcoma. The name is derived from the suggestion that they arise from pluripotential ectomesenchyme. An English language literature search revealed 11 other cases that arose in soft tissue and had adequate clinicopathologic data. Of the 13 cases, 10 occurred in infants, three occurred in adults, and nine were males. Six patients were alive and free of disease at last follow-up (range, 0.6-12 years; mean, 3.4 years), four patients had died of tumor (within 0.5-3.3 years; mean, 1.3 years), one case had died of Adriamycin (doxorubicin) toxicity, and two cases had been lost to follow-up. Complete surgical resection is the mainstay of treatment and chemotherapy appears to be important.

Sarcomatoid carcinomas are typically (but not always) biphasic tumors containing both carcinomatous and sarcomatous components. Within the upper aerodigestive tract, they arise from the mucosa and are predominantly composed of pleomorphic spindled cells associated with squamous carcinoma, the latter often presenting focally at the tumor base. Although their histogenesis is still debated, most authors favor metaplastic origin of the sarcomatous cells from carcinoma cells. Indeed, when studied with electron microscopy and/or immunohistochemistry the sarcomatous cells are frequently found to retain epithelial features; however, the sarcomatous metaplasia can be so complete that malignant cartilage, bone, and/or muscle cells are formed. In addition, metastatic deposits may contain sarcomatous and/or carcinomatous components. Sarcomatoid carcinomas are potentially aggressive tumors and should be treated accordingly. Although it is difficult to predict biologic behavior in every case, patients whose tumors are deeply invasive tend to have a poor prognosis, whereas those with superficially invasive tumors usually have an excellent prognosis.

The accuracy of Masson's trichrome stain to predict the presence of immune complexes was determined in 63 renal biopsies. When immunofluorescence was defined as the reference method, the histologic method correctly predicted the presence or absence of deposits in 70% of biopsy specimens, while electron microscopy was accurate in 79% of specimens. This difference was not statistically significant. The commonest error in our assessment of the Masson's trichrome-stained specimens was the erroneous interpretation of specimens showing minimal change nephropathy or ischemic glomerulopathy by immunofluorescence and electron microscopy. This resulted in a falsely positive diagnosis of one or another of the glomerulonephritides in 13% of cases. Thus, the routine study of renal biopsies with Masson's trichrome stain is clearly useful and should be applied with caution, but it does not replace electron-microscopic and immunofluorescence studies.

Subcutaneous granuloma annulare is a rare scalp lesion that occurs in infants and children. Occurrence in the occipital region, absence of bone involvement, slow growth, and foci of necrosis of collagen surrounded by palisading granulomatous inflammation are characteristic of this lesion. Although the cause remains unknown, it is not infectious and is more likely due to a defect in cell-mediated immunity. The prognosis after excision is excellent. Increased awareness that this peculiar granulomatous lesion can rarely occur in the soft tissue of the occipital region will help prevent confusion with neoplastic or infectious processes.

A two-year-old child with the clinical stigmata of nail-patella syndrome, congenital urinary tract anomalies and proteinuria underwent renal biopsy. Electron microscopy revealed characteristic electron lucent areas and collagen fibril-like deposits in the glomerular basement membrane. Of special interest, electron dense deposits were seen in subendothelial areas of the capillary loops and immunofluorescent staining was striking, particularly for IgM, in a peripheral capillary loop pattern.

After using a cellular digestion technic to extract cells from the basement membranes of frozen kidney tissue, we used scanning electron microscopy to examine the acellular glomerular basement membranes (AGBM) and acellular tubular basement membranes (ATBM) from normal kidneys and from the kidneys of patients with lupus nephritis. This method revealed, in the AGBM, previously unrecognized three-dimensional patterns of pathologic changes. These patterns correlated with the World Health Organization (WHO) subclass of lupus nephritis and with the quantity of immune-complex deposition seen with two-dimensional microscopy. These pathologic changes included epimembranous, crater-like deformities with and without material resembling immune complexes; severely distorted, "moth-eaten" glomerular basement membrane; and the formation of secondary basement membrane within glomerular capillaries. We did not see similar abnormalities in the ATBM.

Reported are two cases of oncogenic osteomalacia, each caused by a small mesenchymal tumor, with detailed assessment of the tumors by light microscopy, electron microscopy, and immunohistochemistry. One tumor was a primitive mesenchymal tumor with prominent giant cell and vascular components, and the second resembled the giant cell variant of soft parts chondroma. Osteoclast-like, multinucleated giant cells and vascularity were prominent features in both tumors. Although the literature documents a histologically heterogeneous group of tumors as causing this syndrome, most have multinucleated giant cells and/or extensive vascularity. The high incidence of these two histologic features in this group of tumors suggests that either or both may be related to the pathogenesis and/or metabolic consequences of oncogenic osteomalacia/rickets.

Reported are the pathologic features of 17 mesenchymal tumors documented as causing osteomalacia or rickets. Although these tumors were histologically polymorphous, they were classifiable into four morphological groups. In the first group there were ten unique tumors showing mixed connective tissue features and containing variably prominent vascular and/or osteoclast-like giant-cell components. Tumors of this group also displayed focal microcystic changes, osseous metaplasia, and/or poorly developed cartilaginous areas. The cartilaginous areas sometimes showed considerable dystrophic calcification. With one exception, all tumors of this group occurred in soft tissue and demonstrated benign clinical behavior. The single malignant tumor originated in bone, recurred locally, and metastasized to lung. The tumors comprising the remaining three groups (six tumors) occurred in bone, demonstrated benign clinical behavior, and were grouped according to their close resemblance to tumors known to occur in bone, that is osteoblastoma-like (four tumors), nonossifying fibroma-like (two tumors), and ossifying fibroma-like (one tumor).

After using a cellular digestion technique to extract cells from the basement membranes of frozen kidney tissue, we employed scanning electron microscopy to examine the acellular glomerular basement membranes (AGBM) from normal kidneys and from kidneys of patients with idiopathic membranous glomerulopathy (MGN). This method revealed, in the AGBM, previously unrecognized three-dimensional patterns of pathologic changes. These patterns correlated with increasing MGN stage as defined by Ehrenreich and Churg. On the epimembranous AGBM surface these patterns were composed of ridge-like trabeculae, irregular plaques, and reticulated crater-like deformities. The endothelial AGBM surfaces were smooth in stages I and II MGN, but in stage III MGN the endothelial surfaces were irregular and perforated. In contrast to lupus-related MGN, where some immune-complex-like material remained after cellular extraction, epimembranous immune-complex-like material in idiopathic MGN was extracted.

Pseudoangiomatous hyperplasia of mammary stroma (PHMS) is a benign proliferation of keloid-like fibrosis, containing slit-like pseudovascular spaces. Its main importance is its distinction from angiosarcoma; however, the clinicopathologic spectrum of PHMS remains incompletely described. We report two new cases and describe our findings in 200 consecutive breast specimens evaluated for the presence of PHMS. The first patient presented with peau-de-orange change in the overlying breast skin, thus mimicking inflammatory breast carcinoma. Furthermore, this patient's PHMS lesion had been diagnosed and treated inappropriately as a low-grade angiosarcoma. The second case showed the more typical, fibroadenoma-like presentation of PHMS. In addition, PHMS changes occur commonly in routine breast biopsy specimens. In fact, our review of 200 consecutive breast specimens showed PHMS in at least one microscopic focus in 23% of cases. The PHMS changes occurred in younger patients than the control population and were associated with fibrocystic changes, in fibroadenomas, in gynecomastia, in normal breast tissue, and in sclerosing lobular hyperplasia. Ultrastructural and immunohistochemical studies of one case showed that the capillary-like spaces were either acellular or lined by fibroblasts. Pseudoangiomatous hyperplasia of mammary stroma represents a clinicopathologic spectrum, extending from focal, insignificant microscopic changes to cases where PHMS produces a breast mass. Increased awareness of PHMS and its clinicopathologic spectrum will allow its differentiation from other vascular tumors of the breast, especially low-grade angiosarcoma.

Although mass lesions of the salivary glands are readily accessible to examination by fine-needle aspiration, the use of this modality has been limited. In part, this may be related to the difficulty differentiating between benign and malignant neoplasms in some cytologic specimens. Marked atypia in reactive non-neoplastic epithelium also could result in a false-positive diagnosis. In addition, aspiration of hypocellular material from cystic neoplasms, eg, well-differentiated mucoepidermoid carcinoma, may lead to false-negative cytologic reports. However, the diagnostic specificities claimed by a number of authors for this method are excellent. Furthermore, aspirates of certain specific neoplasms may yield highly distinctive cellular samples, such as the uniform tumor cells and extracellular hyaline spheres in many adenoid cystic carcinomas. Another example is the characteristic transition between the epithelial and myoepithelial cells of pleomorphic adenomas, which may contain prominent myxoid matrical material. With the increasing recognition of such features, the reported levels of diagnostic accuracy are improving.

Development of microcalcifications at the primary excision site of the irradiated breast is a common manifestation of local tumor recurrence. The authors describe the mammographic appearances of benign suture calcifications, which, in some cases, can mimic recurrence on routine follow-up mammograms and include (a) a typical, knotted configuration, (b) a smooth, linear type, or (c) an apparent indeterminate cluster, which, when imaged with magnification technique, exhibits a more typical appearance. Pathologic examination demonstrates calcifications in the dead collagen that makes up catgut suture. Knowledge of these appearances and use of magnification technique in the evaluation of microcalcifications at the primary excision site may prevent unnecessary biopsy.

The EMIT technique for theophylline measurement as adapted to the Abbott Bichromatic Analyzer (ABA-100), was compared to two other established procedures. EMIT results correlated well with those obtained with high pressure liquid chromatographic (HPLC) (r = 0.995, N = 54) and spectrophotometric (UV) (r = 0.95, N = 37) methods when the patient samples used were free of apparent interferences in the comparison methods. On samples exhibiting interferences with HPLC and/or UV methods, the EMIT assay gave the same results as a gas-liquid chromatographic procedure which showed no interferences. In addition, theophylline metabolites, xanthine analogs and many commonly administered drugs did not interfere with the EMIT theophylline assay. An interassay coefficient of variation of 3.5--6.5% was demonstrated. Our data indicate that the EMIT technique exhibits adequate precision and specificity for routine theophylline determinations. Unlike the HPLC or UV procedures, we have not encountered any interferences with the EMIT technique.

The effect of intravenous administration of homologous fibrin degradation products and thrombin on fibrinogen synthesis was assessed in rabbits. The relative fibrinogen synthesis rate was calculated as a ratio of the amount of radiolabelled lysine incorporated into fibrinogen to the amount incorporated into albumin during the same measurement period. An increase in this ratio above control would indicate a relatively specific stimulation of fibrinogen synthesis as compared with albumin, which is not an acute-phase reactant. Injection of 45 mg of 'early' or 'late' fibrin degradation products failed to produce a significant increase in the relative fibrinogen synthesis rate, suggesting that fibrin degradation products play no feedback role in controlling fibrinogen synthesis. Infusion of small amounts of homologous thrombin (15--25 NIH u) was followed by a small but statistically significant elevation of the relative fibrinogen synthesis rate. This was not accompanied by any increase in the levels of fibrinogen degradation products in plasma, or by any decrease in plasma fibrinogen concentration, possibly suggesting that thrombin can stimulate fibrinogen synthesis by a mechanism independent of significant fibrinogenolysis or intravascular coagulation.

Two unusual cases of squamous cell carcinoma (SCCa) metastatic to skin from distant sites occurred. In both metastatic sites, the malignant squamous epithelium fused with benign surface epithelium, and the resulting transition simulated that typically seen in primary cutaneous SCCa. We believe that this previously unreported phenomenon is an expression of the natural tendency of squamous epithelium to "heal" denuded connective tissue surfaces by proliferation followed by epithelial fusion. Because epithelial continuity can be established between benign keratinocytes and metastatic SCCa, one cannot rely on this single morphologic finding to separate primary from metastatic disease.

The cytogenetic analysis of a well-differentiated (grade I) chondrosarcoma is presented. Despite a low-grade histopathology, metaphase preparations of tumor cells were characterized by numerous structural chromosome aberrations and a striking degree of genetic instability; the t(9;22)(q31;q12) that has been described recently in extraskeletal myxoid chondrosarcoma was not observed. This report suggests that chondrosarcomas may be heterogeneous cytogenetically. In chondrosarcoma, it appears that "high-grade" cytogenetic abnormalities do not necessarily engender a high-grade histology. These findings offer a possible explanation for the clinical aggressiveness of certain low-grade chondrosarcomas.

To develop histologic criteria that allow distinction of prolapsed from nonprolapsed intervertebral disk material, we reviewed the histologic features of curetted fibrocartilage from 100 consecutive patients having documented disk prolapse into the spinal canal and contrasted our findings to those in 40 intervertebral disks removed at autopsy from 20 patients without prolapse. Neovascularization, occurring at the edges of fibrocartilage fragments, was present in 50% of prolapsed disk specimens and in none of the control autopsy disks (p = 0.0004). Other histologic features sometimes used as evidence of degeneration and/or prolapse (i.e., fibrillation, chondrocyte "cloning," and granular change) were not helpful in distinguishing prolapsed from nonprolapsed control disks. Although this indicator was only 50% sensitive in our series, we propose that edge neovascularization of the fibrocartilage fragments is the only reliable histologic clue that intervertebral disk prolapse has occurred.