A case of von Recklinghausen's disease with bilateral pheochromocytoma-malignant peripheral nerve sheath tumors of the adrenal and gastrointestinal autonomic nerve tumors.

A 48-year-old man with neurofibromatosis type 1 presented with chest pain, paroxysmal hypertension, tachycardia, and progressive respiratory insufficiency. Clinical investigation displayed calcified tumors in the anterior mediastinum and pararenal region. Histological examination at autopsy revealed composite tumors consisting of pheochromocytoma and malignant peripheral nerve sheath tumor (MPNST) at two sites: the left adrenal gland and the region surrounding the inferior vena cava, probably corresponding to the right adrenal gland. The MPNST component showed a varied histological appearance, including hyalinized bands with polygonal cells, a cartilaginous and myxoid stroma, a hemangiopericytomatous architecture, and a fibrosarcomatous structure, which suggested osteosarcoma, chondrosarcoma, angiosarcoma, and fibrosarcoma, respectively. In addition, based on the ultrastructural findings, the gastrointestinal tract was involved with mesenchymal tumors showing neurogenic differentiation. These lesions suggest the divergent cellular differentiation of neural crest-derived cells to mesenchymal elements as well as neuroectodermal neoplasms.

Proliferative activity of hepatocytes in chronic viral hepatitis as revealed by immunohistochemistry for proliferating cell nuclear antigen.

Liver biopsy specimens of 65 cases of chronic viral hepatitis, including 29 cases of type B, 34 cases of type C, and two cases of non-A, non-B, non-C type, were immunohistochemically stained for proliferating cell nuclear antigen (PCNA) to evaluate the proliferative activity of hepatocytes. According to a histopathologic evaluation using the histology activity index (HAI) scoring system, chronic persistent hepatitis and chronic active hepatitis were clearly differentiated with no overlapping of the score. The labeling indices of PCNA of hepatocytes in chronic persistent hepatitis had a significant relationship with HAI scores (r = .54), suggestive of a contribution of lobular hepatocyte necrosis and/or portal inflammation to the regenerative rate of hepatocytes, but did not exceed 3.0%. On the other hand, 11 of 47 cases of chronic active hepatitis showed PCNA labeling indices higher than 3.5% without any significant relationship with the HAI scores. There was no significant difference, however, of distribution of HAI scores or PCNA labeling indices between hepatitis types B and C. Based on current concepts of the role of hepatocyte proliferation in the development of liver cirrhosis and hepatocellular carcinoma, the present results suggest that the high proliferative rate of hepatocytes subject to the persistent liver cell injury in chronic active hepatitis may be related to a reconstruction pattern of the liver in cases of progression to cirrhosis and development of hepatocellular carcinoma.

Diagnosis of systemic mycoses by specific immunohistochemical tests.

Immunohistochemistry has proved to be a powerful tool for the accurate diagnosis of a number of important mycoses in humans and animals, such as aspergillosis, candidosis, cryptococcosis, blastomycosis, coccidioidomycosis, histoplasmosis capsulati and duboisii, paracoccidioidomycosis, fusariosis, pseudallescheriosis (scedosporiosis), sporotrichosis, trichosporonosis, penicilliosis, and zygomycosis (mucormycosis). These techniques are also applicable to pneumocystosis and to non-mycotic infections caused by algae such as protothecosis. Apart from the specificity of immunohistochemistry, the application of fluorochromes is highly effective for the localization of typical or atypical fungal elements in lesions with only few organisms present. Occasionally, a dual aetiology of fungal infections may be suspected on the basis of morphological study, and dual staining techniques have the capacity for resolving this question by simultaneous and differential staining of two fungal species present in a tissue specimen.

Present state of fungal infections in autopsy cases in Japan.

In order to clarify the present state of opportunistic fungal infections increasing in incidence in autopsy cases, all autopsy cases from 1966 to 1975 reported in the Annual of Pathological Autopsy Cases in Japan were reviewed. Of the total 233,130 autopsy cases, mycoses were present in 4,340 (1.86%). The incidence of mycoses has strikingly increased during the recent five-year period. In Japan, the mycoses most frequently occurring in autopsy cases were candidiasis (32.28%), aspergillosis (23.08%), cryptococcosis (9.63%), and mucormycosis (2.90%). These occurred more frequently in younger persons and were most commonly secondary and deep-seated infections (95.78%). Among the primary diseases associated with mycoses, aplastic anemia (14.36%), leukemia (9.89%), malignant lymphoma (5.73%), multiple myeloma (4.68%), and systemic lupus erythematosus (4.62%) were most frequent. The incidence of the primary diseases associated with mycoses is increasing extraordinarily, and this seems to be strongly related to the modern therapy of using high doses of anticancer or immunosuppressive agents.

Improved detection of medically important fungi by immunoperoxidase staining with polyclonal antibodies.

This study was performed to identify pathological fungi of eight species [Aspergillus fumigatus, Candida albicans, Torulopsis (Candida) glabrata, Cryptococcus neoformans, Fusarium anthophilum, Rhizopus oryzae, Sporothrix schenckii and Trichosporon beigelii] in formalin-fixed, paraffin-embedded tissue sections by indirect immunoperoxidase staining. Mature albino rabbits were immunized with formalin-killed organisms. Antibodies were prepared by precipitation. Immunoperoxidase staining was applied to the paraffin-embedded tissue sections of experimentally infected mice and human autopsy and surgical specimens. Although the cell walls of each fungus stained clearly, many cross-reactivities appeared. However, it was possible to obtain specificity for the eight species by absorption and dilution of the antisera.

Disseminated Candida tropicalis infection following endoscopic retrograde cholangiopancreatography.

A necropsy case of a 59-year-old man who developed disseminated Candida tropicalis infection following endoscopic retrograde cholangiopancreatography (ERCP) is reported. Septic fungal infection complicating ERCP has not been described previously.

Localized necrotizing arteritis. A report of two cases involving the gallbladder and pancreas.

We report two cases of localized necrotizing arteritis, one involving the gallbladder and one involving the pancreas. Both cases were found incidentally in surgically resected specimens. Vascular changes in both cases were similar to those seen in classic polyarteritis nodosa, involving medium-sized muscular arteries characterized by fibrinoid necrosis and panarterial and periarterial inflammations varying from active to resolving stages. Both patients had no constitutional symptoms or underlying serologic abnormalities suggestive of systemic angitis. To our knowledge, pancreas-limited arteritis has not previously been described. Whether these lesions represent an early manifestation of a systemic arteritides syndrome, a variant of polyarteritis nodosa, or a distinct entity should be prudently judged through a long-term follow-up.

Angiomyofibroblastoma of the male inguinal region.

We present a case of benign angiomyxoid tumor arising in the inguinal region of a 27-year-old man. The tumor was a gelatinous mass completely encapsulated by a thin fibrous capsule with no hemorrhage or necrosis. Histologically, a proliferation of spindle cells as well as occasional pleomorphic cells was observed within the myxofibrous stroma, intermingled with abundant capillary-sized blood vessels. Immunohistochemical staining of the tumor demonstrated spindle, oval, and pleomorphic cells equally positive for vimentin, desmin, and CD34, but not for alpha-smooth muscle actin. Based on these histologic and immunophenotypic features, we conclude that this angiomyxoid tumor of the male inguinal region is indistinguishable from the female angiomyofibroblastoma of the pelvic and perineal regions.

Diagnostic value of serum antibody to candida in an extensively burned patient.

This report gives details of an extensively burned patient who died of candidiasis. Retrospectively, by using the procedure of indirect immunoperoxidase staining, we measured the levels of antibody to candida in the stored patient's serum, collected from the time of admission to our hospital until death. Gradual increases in the antibody titres to candida were seen over the postburn period. The findings can be useful in diagnosing candidiasis.

Histochemical demonstration of DNA double strand breaks by in situ 3'-tailing reaction in apoptotic endometrium.

A new histochemical technique, called in situ 3'-tailing reaction (ISTR), to detect DNA double strand breaks (DSB) was developed and applied to tissue sections of apoptotic endometrium. To demonstrate DSB, biotin-labeled and unlabeled dATPs with terminal deoxynucleotidyl transferase (TdT) were added to the many 3-hydroxyl termini of DNA fragments generated in the apoptotic cells. For an efficient 3'-end labeling, it was necessary to treat the sections with lambda-exonuclease (lambdaEx) prior to the TdT reaction to generate 3'-protruding ends. The lambdaEx-TdT reaction specifically labeled nuclear fragments in the apoptotic cells in paraformaldehyde fixed frozen sections. In paraffin sections, pretreatment with proteinase K was effective for 3'-tailing reaction. ISTR should be a useful tool for detecting dying cells in both physiological and pathological states.

Subcutaneous mucormycosis seen after gypsum fixation for bone fracture.

A patient with erythema on the dorsum of the left foot after the removal of gypsum fixation applied for the treatment of bone fracture is reported. Both the clinical and histopathologic features led to the diagnosis of mucor infection.

[An autopsy case of HELLP syndrome with disseminated aspergillosis].

Disseminated aspergillosis is an uncommon and unpredictable complication in severely immunocompromised patients and poses a challenging problem in the management and care of seriously ill patients receiving intensive care therapy. We report an autopsied case of disseminated aspergillosis occurring ina 31-year-old female patient who was treated for HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. She initially presented with edema and proteinuria at a pregnancy check-up. At gestational age 33 weeks and 2 days, she had right lower abdominal pain, nausea, and jaundice. The next day she delivered a male neonate transvaginally, followed by excessive postpartum uterine bleeding. Although an emergency hysterectomy was performed, her hemorrhagic diathesis could not be controlled even after transcatheter embolization of the internal iliac arteries with subsequent ligation and repeated blood transfusions totalling to 31,070 ml. She eventually died of a cerebral hemorrhage 21 days after the parturition. Autopsy showed generalized jaundice and petechiae, as well as extensive hemorrhage observed in the abdominal wall, peritoneal cavity, and retroperitoneal and pelvic spaces. In addition,there were multifocal hemorrhages found in the left temporal, right frontal and posterior lobes of the cerebrum, and pons. Disseminated aspergillosis was found in the lungs, trachea, brain, esophagus, stomach, heart, and thyroid gland. These findings suggest that systemic postoperative complications, associated with massive blood transfusions and hepatic failure, mutually contribute to the overall deterioration of host defense mechanism, and may underlie the occurrence of devastating systemic fungal infection.

[Intractable vasculitis: general consideration-concept and classification: pathological aspects].

Vasculitis may be defined as an inflammatory process, primarily affecting the vascular wall which possesses an architecture, such as organ or tissue, and accordingly may not include the capillary. Since the walls are destroyed, secondary circulatory disturbances may be associated and produce vasculitic symptoms, which are nonspecific in most instances. Although the pathogenesis of most vasculitides is well understood, the lack of knowledge of the etiology makes it difficult to establish a satisfactory classification of vasculitis. The inflammatory lesions tend to be distributed along the course of the vessels throughout the body in most systemic vasculitic syndromes but long segments are frequently affected in the arteritides of large arteries. In recent years, a classification, useful for understanding the clinical manifestations of these vasculitic disorders, is based on the predominant size of the involved vessels, which may be categorized into large arteries (aorta and its primary branches), medium-sized to small muscular arteries and small vessels (arterioles and venules). Certain vasculitides may occur as a primary disease process, whereas others may be associated with other primary disorders. In general, idiopathic primary vasculitides have an extremely poor prognosis and are intractable. However, recent advances of drug therapies in the early stage of the systemic necrotizing vasculitides, such as Wegener's granulomatosis, has bettered prognosis. In the patients with Takayasu's arteritis, life has been prolonged over more than ten years. As a result, additional problems, such as luminal stenosis or dilatation of the involved vessels, have occurred.