Histological diversity of vasculitic lesions in MPO-ANCA-positive autopsy cases.

To investigate the variety of histological features of vasculitic lesions in myeloperoxidase-specific antineutrophil cytoplasmic antibody (pANCA)-related vasculitis, retrospective pathological analysis was done on 13 autopsy cases, collected from 1990 to 1998 at five hospitals. These cases were classified into three groups: (i) pulmonary-renal syndrome characterized by capillaritis of lung and glomeruli with occasional small-vessel arteritis and/or phlebitis; (ii) glomerular capillaritis without pulmonary involvement associated with significant small-vessel arteritis; and (iii) extensive distribution of small-vessel arteritis with no capillary involvement. The results suggest that pANCA-related vasculitis encompasses a wide variety of vasculitic syndromes, including pulmonary-renal syndrome, microscopic polyarteritis nodosa, and classic polyarteritis nodosa. pANCA may contribute to pathogenesis in all of these cases.

A rat model of hypereosinophilic syndrome.

Hypereosinophilia-occurring rats without chemical and antigen treatment have been maintained in our laboratory. The rat, Matsumoto Eosinophilia Shinshu (mes), showed hypereosinophilia at the age of 9 weeks or older and developed eosinophil-related inflammatory lesions in many organs. These lesions included: aortitis, granulomatous lesion in the mesenteric lymph node, inflammatory fibroid polyp of the stomach and pulmonary vasculitis with septal infiltration. These lesions were involved with cellular infiltration of eosinophils and macrophages, and deposition of eosinophilic crystals which immunohistologically showed major basic protein and eosinophilic peroxidase derived from eosinophilic lysosomal constituents. Although the distribution of lesions in mes is a little different from that of hypereosinophilic syndrome (HES) in humans, in that endomyocardial fibrosis appears in HES while aortitis appears in mes, mes is probably comparable with HES. The present paper describes the pathological aspects of the lesions in mes and discusses the pathogenesis of tissue injury related to eosinophilic infiltration.

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.

[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.

Application of short tandem repeat of genomic DNA and mitochondrial DNA for identification of mixed-up tissue specimens.

Deoxyribonucleic acid (DNA) typing methods, short tandem repeat of genomic DNA and mitochondrial DNA with the use of polymerase chain reaction amplification, were applied to formalin-fixed, paraffin-embedded tissues submitted for diagnosis, to identify and sort out mixed-up tissue specimens. These techniques were found to be reliable, reproducible and specific for personal identification, and thus to eliminate the need for further examinations and to prevent unnecessary surgery.

Disseminated Fusarium infection identified by the immunohistochemical staining in a patient with a refractory leukemia.

The difficulty and uncertainty encountered in diagnosing a systemic mycosis often lead to a delay in starting antifungal therapy. We reported a disseminated infection of multiple fungal isolates including Fusarium species during donor leukocyte transfusion (DLT) after allogeneic bone marrow transplantation in a 20-year-old woman with a refractory leukemia. Skin lesions are the feature of Fusarium and occur in the early period of the infection. In this case, during immunosuppression state after DLT, she presented with the whole body ache and erythematous lesions which appeared rapidly on her trunk and extremities. While administration of amphotericin B was started, her condition was further deteriorated and she died. Autopsy materials revealed that she had multiple fungal infection with different isolates, including Aspergillus and Candida in the brain, lung and liver, but not in the skin. With the immunohistochemical staining with specific antibody, Fusarium or Aspergillus infection was identified from the biopsy skin or autopsy brain, respectively. This rapid and specific immunohistochemical method may be useful for the diagnosis and treatment of invasive fungal infection without delay.

Intravascular fasciitis of the forearm vein: a case report with immunohistochemical characterization.

Intravascular fasciitis is a very unusual variant of nodular fasciitis. A unique case of this lesion occurring in the proximal portion of the superficial vein of the forearm in an otherwise healthy 26-year-old man is reported. The intravascular polypoid lesion grew longitudinally along the vascular lumen, was loosely attached to the intimal layer, and was partly anchored beyond the internal elastic lamina into the medial smooth muscle layer. However, extravascular involvement was absent. The histological features were identical to those observed in ordinary cellular nodular fasciitis. Because of its myofibroblastic phenotype exhibited by highly proliferative spindle cells, certain intimomedial myofibroblasts are thought to be the indigenous source of this unique fibroproliferative lesion. Unless the diagnosis of intravascular fasciitis is considered and appropriate differential markers examined, it may be confused with other intravascular lesions, such as intravascular leiomyoma, intravenous pyogenic granuloma, organized thrombus and, even, fibromuscular dysplasia if it arises in the arteries. A simple excision is considered curable. Even so, two recurrent cases have been documented to date.

Pityriasis versicolor with a unique clinical appearance.

We experienced an atypical case of pityriasis versicolor with a unique clinical appearance and undescribed mycological features. Although Malassezia sp. was cultured from the keratotic material, the fungal elements observed in the material were not readily identified as Malassezia. The diagnosis was established with the aid of immunohistochemical and ultrastructural studies with the aetiological agent being identified as M. globosa.

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.

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.

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.

Intussusception of the appendix: a report of three cases with different clinical and pathologic features.

Three cases of intussusception of the appendix (IA) with distinctive pathologic changes were reported. All patients were women with different clinical presentations. Grossly, a complete intussusception was found in one case (case 1), while the others (cases 2 and 3) showed a partial intussusception. In case 1, almost the total segment of the appendix bearing the villous adenoma with focal malignant transformation became completely telescoped into the cecum. In case 2, no underlying appendiceal lesion was disclosed. In case 3, appendiceal endometriosis was found as the point of traction. Awareness of such a rare complication associated with various appendiceal lesions provides a clue for making an accurate diagnosis and selecting appropriate surgical management.

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.

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.

[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.

Malignant paraganglioma presenting as Cushing syndrome with virilism in childhood. Production of cortisol, androgens, and adrenocorticotrophic hormone by the tumor.

BACKGROUND: A 12-year-old girl with intractable retroperitoneal paraganglioma experienced increased appetite, acne, obesity, "moon face," and enlargement of the clitoris during the course of the tumor. Plasma cortisol, serum testosterone, and dehydroepiandrosterone sulfate (DHEA-S) levels were increased to 34.1 micrograms/dl, 2.0 ng/ml, and 6.628 ng/ml, respectively. Adrenocorticotrophic hormone (ACTH) levels were not increased, and results of dexamethasone suppression tests were negative. Her condition was diagnosed as Cushing syndrome with virilism. Plasma cortisol levels were increased to a level of 107.1 micrograms/dl before death. METHODS: Tumor samples were obtained at the time of autopsy. The concentrations of cortisol, androgens, ACTH, and catecholamines were assayed in the tumor extracts. The indirect immunoperoxidase procedure was performed on fixed tissues for cortisol, DHEA-S, testosterone, and ACTH. RESULTS: Extracts of the tumor masses contained steroid hormones: the amount of immunoreactive cortisol was 1.64 micrograms/g wet weight; the amount of immunoreactive testosterone was 25.60 ng/g wet weight; immunoreactive DHEA-S, 579.00 ng/g wet weight; and immunoreactive ACTH, 891.00 pg/g wet weight in the metastatic mass of the lung. Immunohistochemically, immunoreactive cortisol, testosterone, and DHEA-S were detectable in the tumor cells. The adrenal gland was atrophic. CONCLUSIONS: The patient is the first reported with malignant paraganglioma with the capacity to produce cortisol, androgens, and ACTH.

Immunohistochemical, electron microscopic, and immunoelectron microscopic features of plasmacytoma of the thyroid with amyloid deposition.

A rare case of primary plasmacytoma of the thyroid with amyloid deposition is reported. The tumor consisted of diffuse proliferation of atypical plasma cells showing IgG lambda-type monoclonal growth. Amyloid deposition with focal giant cell reaction was also observed. Bone marrow aspiration and systemic skeletal radiographic surveys revealed no evidence of multiple myeloma and myelomatosis. Radial arrangement of amyloid bundles was observed ultrastructurally. By immunoelectron microscopic examination, lambda chain was detected in the amyloid fibrils and rough endoplasmic reticulum of the tumor cells. Our findings suggest the following: amyloid fibrils originate from monoclonal light chains produced by tumor cells, and histiocytes contribute to amyloid deposition as well as to giant cell reaction in extramedullary plasmacytoma.

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.

Epithelioid hemangioendothelioma of the liver diagnosed by liver biopsy under laparoscopy.

We report a case of primary epithelioid hemangioendothelioma arising in the liver. There were no specific findings or signs except for the deformity and multiple lesions of the liver at imaging procedures, which included magnetic resonance imaging. The key to the diagnosis was histological examination of liver biopsy specimens obtained under laparoscopy. Plasma factor VIII activity was elevated, which was also helpful in the diagnosis.