IgG4-related disease involving the esophagus: a clinicopathological study.

Immunoglobulin G4 (IgG4)-related disease is a recently coined systemic disease characterized by specific histopathologic findings of an intense lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis in the presence of predominant IgG4-positive plasma cells. Although IgG4-related disease has been described in many organs, involvement of the esophagus is very rare. In this study, we describe the clinicopathologic characteristics of eight patients with IgG4-related esophagitis. We evaluated chronic esophagitis specimens with lymphoplasmacytic infiltrate obtained over the past 6 years (from January 2011 to February 2017) using a chart review, pathologic examination, and IgG4 immunohistochemical staining. The diagnoses of the specimens were either confirmed as IgG4-related esophagitis (IgG4-RE) or chronic esophagitis, not otherwise specified (CENOS), and the clinicopathologic data from each group were compared. Eight patients were diagnosed with IgG4-RE and 10 controls were identified and diagnosed with CENOS. In the IgG4-RE group, esophageal strictures were identified in three patients, two patients had postmyotomy treated achalasia, one patient had erosive esophagitis and another presented with an esophageal nodule. Only one patient had an unremarkable mucosa on endoscopy. In the CENOS group, four patients had esophageal strictures, six had erosive esophagitis, one patient had mild esophagitis. The IgG4-RE group had significantly higher numbers of IgG4-positive plasma cells (66.9 ± 21.9 vs. 4.7 ± 2.4 per high power field; P< 0.001) and a greater IgG4: IgG ratio 0.76 ± 0.13 vs. 0.06 ± 0.05; P< 0.001) when compared to CENOS patients. Two of the patients with recurrent esophageal strictures in the IgG4-RE group showed initial response to steroid therapy and are currently on immunosuppressive therapy which has significantly reduced the need for multiple esophageal dilatations. The presentation of IgG4-related esophageal disease can vary and the key to diagnosis is dependent on histopathology. These observations highlight the need for IgG4 immunohistochemical staining of esophageal biopsies especially in patients with mucosal ulceration, chronic inflammation, and plasmacytosis on biopsy. This will prevent unwarranted esophagectomies and failed medical treatment due to lack of recognition of this entity.

Occult leptomeningeal large cell medulloblastoma in an adult.

OBJECTIVE AND IMPORTANCE: Large cell medulloblastoma is an uncommon malignancy of childhood that often pursues an aggressive clinical course. We report the first case of this entity in an adult that proved to be an unsuspected primary leptomeningeal tumor. CLINICAL PRESENTATION: A 30-year-old man complained of worsening neck pain over the course of 3 months. Neck pain increased a few days prior to admission and a cervical spine CT revealed tonsillar herniation. Cervical spine MRI performed the day prior to admission confirmed the diagnosis of Chiari I malformation and C3-4 disk herniation without spinal cord compression. On the day of admission, the patient became unresponsive and resuscitative measures were unsuccessful. Postmortem examination of the brain was notable for necrotic cerebellar tonsils, but demonstrated no evidence of an intraparenchymal mass lesion. Microscopic examination of the cerebellum revealed discohesive neoplastic cells, which showed characteristic dot-like immunoreactivity for synaptophysin, diagnostic of large cell medulloblastoma within the subarachnoid space. CONCLUSIONS: Our experience with this unique case illustrates the challenges of diagnosing a primary leptomeningeal neoplasm. This case also underscores the importance of maintaining a high degree of suspicion for leptomeningeal neoplasms in patients who present with imaging studies suspicious for Chiari I malformation.

Performance verification of a precise vibrating-wire magnet alignment technique for next-generation light sources.

The high-accuracy alignment of magnets is a key issue in the development of next-generation light-source rings. To obtain adequate dynamic apertures, the magnets must be aligned to an accuracy of 10 µm or better. Recently, a new technique that utilizes a vibrating wire has attracted attention for this purpose as it can directly determine with high resolution the magnetic centers in a series of multipole magnets on a straight section between bending magnets. In conventional vibrating-wire alignment techniques, wire sag, which causes alignment errors, is determined from the theoretical catenary curve. By contrast, in the present study, we have measured the sag profiles of various wires in the longitudinal direction to micrometer-order accuracy. We concluded that we can reduce deviations of the actual wire sag from the theoretical curve by choosing a suitable wire. By setting up a test bench of a vibrating-wire alignment system for a series of multipole magnet on a straight section, we have achieved the total error of the magnetic-center measurements of micrometer-order in the standard deviation. Moreover, two systematic error factors, the drift of the magnetic centers due to thermal deformations of the magnets after they are excited and the change in the magnetic centers due to reassembly of the magnets after installing the vacuum chamber, are included in practical magnet alignments. We have experimentally investigated these error factors using the test bench.

Carcinogenesis in heterotopic respiratory epithelium in canine subcutaneous bronchial autografts.

Short bronchial segments obtained by pneumonectomy were implanted, 9-12 per dog, in the subcutaneous tissues of the back of seven dogs. These subcutaneous bronchial autografts (SBA) became vascularized, and they contained viable, histologically normal respiratory epithelium 4 wk after implantation. From 1-3 mo after implantation, 10% methylcholanthrene in steroid suspension medium was instilled into 21 SBAs, and 10% methylcholanthrene in a silicone polymer sustained release implant was placed in 22 SBAs. Ten SBAs were left carcinogen free as controls. SBA contents were examined cytologically at 3-mo intervals. Biopsies were done from 2-32 mo after carcinogen implantation. Progressive preneoplastic changes were noted in all five dogs which received carcinogen. Curetments of five SBAs after 14-mo exposure to methylcholanthrene yielded 10(4)-10(5) cells from each SBA; 40-70% of the cells obtained were at the same stage of atypical squamous metaplasia. At least one SBA in each dog yielded cancer cells by cytological criteria by 19-29 mo after instillation. Biopsy of a grossly abnormal SBA revealed well-differentiated epidermoid carcinoma at 32 mo. The multiple SBA method provides isolated portions of canine respiratory epithelium for the study of chemical carcinogenesis and for the production of sizable preneoplastic cell populations.

Differential susceptibility to bronchial carcinogenesis in syngeneic hamsters.

Previous studies of chemical carcinogenesis in the lung of Syrian golden hamsters have utilized outbred (nonsyngeneic) animals. Using the endobronchial sustained release implant technique, which causes focally originating cancers in outbred hamsters, we studied the course of bronchial carcinogenesis in two varieties of syngeneic Syrian golden hamsters, the LSH and the F1D strains (BIO 15.16 male X BIO 87.20 female). With either 10% benzo(a)pyrene or 10% methylcholanthrene sustained release implants the time course of epithelial transition from normal to neoplastic was the same for F1D hamsters as previously described for outbred hamsters. Using 10% benzo(a)pyrene sustained release implants the incidence of cancers as a function of time was significantly lower (P less than 0.001) in LSH hamsters as compared to outbred and F1D animals. Of 19 tumors transplanted into syngeneic F1D hamsters, 16 have been successfully propagated by serial transplantation. We conclude that (a) F1D hamsters are comparable to outbred animals in the response of their bronchial epithelium to endobronchial benzo(a)pyrene and methylcholanthrene, (b) there are significant differences in susceptibility to bronchial chemical carcinogenesis among hamster strains, thereby giving opportunity to study potential genetic control mechanisms during bronchial carcinogenesis, and (c) F1D hamsters are suitable for studies of lung cancer biology using tumor transplantation methods.

Allelic imbalance of the mutant and wild-type RET allele in MEN 2A-associated medullary thyroid carcinoma.

Germline mutations of the RET proto-oncogene are responsible for the familial tumor syndrome called multiple endocrine neoplasia type 2 (MEN 2) that includes medullary thyroid carcinoma (MTC). Although inherited mutations of RET lead to tumor formation in patients with MEN 2, it is not understood why only selected cells develop into tumors. We have recently shown that duplication of the mutated RET allele or loss of the wild-type allele might represent mechanisms of tumorigenesis in patients with MEN 2A-related pheochromocytoma. We now analysed 19 DNA samples of MTC (15 of which were non-microdissected, four of which were microdissected) from patients with MEN 2A. Using polymorphic marker and phosphorimage densitometry analyses, we found allelic imbalance of the mutated and wild-type RET allele in six of 19 DNA MTC samples. Of note, two of the four microdissected tumor DNA samples showed allelic imbalance of RET, whereas only four of the 15 non-microdissected MTC samples did. These results underscore the significance of microdissection in the analysis of tumor DNA. In our study, some of the non-microdissected tumor DNA samples may have failed to display allelic imbalance of RET, because of contamination of tumor DNA with nonneoplastic DNA or noninformative microsatellite marker analysis. Taken together, our results suggest allelic imbalance between mutated and wild-type RET as a possible mechanism for tumor formation in some patients with MEN 2A-related MTC.

Human herpesvirus 6 (HHV-6) ORF-1 transactivating gene exhibits malignant transforming activity and its protein binds to p53.

The 357 amino acid open reading frame 1 (ORF-1), also designated DR7, within the SalI-L fragment of human herpesvirus 6 (HHV-6) exhibited transactivation of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) promoter and increased HIV-1 replication (Kashanchi et al., Virology, 201, 95-106, 1994). In the current study, the SalI-L transforming region was localized to the SalI-L-SH subfragment. Several ORFs identified in SalI-L-SH by sequence analysis were cloned into a selectable mammalian expression vector, pBK-CMV. Only pBK/ORF1 transformed NIH3T3 cells. Furthermore, cells expressing ORF-1 protein produced fibrosarcomas when injected into nude mice, whereas control cells, expressing either no ORF-1 protein or C-terminal truncated (after residue 172) ORF-1 protein, were not tumorigenic. Western blot analysis of proteins extracted from the tumors revealed ORF-1 protein. Additional studies indicated that ORF-1 was expressed in HHV-6-infected human T-cells by 18 h. Co-immunoprecipitation experiments showed that ORF-1 protein bound to tumor suppressor protein p53, and the ORF-1 binding domain on p53 was located between residues 28 and 187 of p53, overlapping with the specific DNA binding domain. Functional studies showed that p53-activated transcription was inhibited in ORF-1, but not in truncated ORF-1, expressing cells. Importantly, the truncated ORF-1 mutant also failed to cause transformation. Analysis of several human tumors by PCR revealed ORF-1 DNA sequences in some angioimmunoblastic lymphadenopathies, Hodgkin's and non-Hodgkin's lymphomas and glioblastomas. The detection of ORF-1 sequences in human tumors, while not proof per se, is a prerequisite for establishing its role in tumor development. Taken together, the results demonstrate that ORF-1 is an HHV-6 oncogene that binds to and affects p53. The identification of both transforming and transactivating activities within ORF-1 is a characteristic of other viral oncogenes and is the first reported for HHV-6.

Increased expression of matrix metalloproteinases 2 and 9 and tissue inhibitors of metalloproteinases 1 and 2 correlate with poor prognostic variables in renal cell carcinoma.

PURPOSE: Matrix metalloproteinases (MMPs) degrade components of the extracellular matrix and are implicated in tissue remodeling and tumor infiltration. Tissue inhibitor of metalloproteinases (TIMPs) inhibit enzymes of the MMP family and preserve stromal integrity, thus inhibiting tumor migration. Although numerous studies on several human carcinomas have demonstrated a role for MMPs in tumor metastasis and patient survival, their prognostic role in patients with renal cell carcinoma (RCC) has not been well defined. More importantly, the recently documented paradoxical functions of TIMPs have not been characterized in these neoplasms. EXPERIMENTAL DESIGN: Five-microm, formalin-fixed, paraffin-embedded tissue sections from 153 RCCs were immunostained using specific antibodies against MMP2, MMP9, (Novocastra, Burlingame, CA) TIMP1, and TIMP2 (NeoMarkers, Fremont, CA) proteins. Immunostaining was semiquantitatively scored based on intensity and distribution, and results were correlated with histological and prognostic variables. RESULTS: The rates of increased expression of MMPs and TIMPs in RCC were as follows: MMP2, 67%; MMP9, 43%; TIMP1, 46%; and TIMP2, 73%. Each of these four markers individually correlated with histological tumor type with a vast majority of papillary and sarcomatoid RCCs expressing these proteins as compared with clear cell tumors (P range, 0.0001-0.003). Significant coexpression of MMPs and TIMPs was observed (P = 0.0001). Increased immunoreactivity for each of these proteins correlated with high tumor grade (P range, 0.0001-0.01). On univariate analysis, expression of each of these markers correlated with shortened survival (P range, 0.004-0.05). On multivariate analysis, including tumor grade, stage, and all four markers, only advanced stage (P = 0.047) and increased TIMP1 expression (P = 0.007) independently predicted shortened survival. CONCLUSION: Increased expression of MMP2, MMP9, TIMP1, and TIMP2 proteins in RCCs correlate with poor prognostic variables including shortened patient survival. The paradoxical poor prognostic implication of TIMP overexpression complements the recently documented dual function of TIMPs and warrants further investigation.

Carcinoid syndrome caused by an atypical carcinoid of the uterine cervix.

Neuroendocrine tumors of the cervix are rare and are often under- or misdiagnosed. Because these tumors are very aggressive, early diagnosis and subsequent treatment are warranted. We describe a 46-yr-old woman with carcinoid syndrome caused by an atypical carcinoid of the uterine cervix. At age 44, she had dysplasia on Pap smear and underwent total abdominal hysterectomy with the diagnosis of adenocarcinoma. Fourteen months postoperatively, she developed the carcinoid syndrome and was found to have numerous liver metastases. Histological and immunohistochemical investigations of biopsy specimens from the patient's liver lesions and original cervical lesion ("adenocarcinoma") suggested that this woman had a primary atypical carcinoid of the uterine cervix with metastases to the liver. Treatment with octreotide and alkylating agents decreased the episodes of flushing and diarrhea within 8 weeks. If an adenocarcinoma of the uterine cervix is diagnosed, atypical carcinoid should be in the differential diagnosis. Symptoms of the carcinoid syndrome should be pursued and, if present, a urinary 5-hydroxyindolacetic acid level should be obtained. Timely diagnosis of a neuroendocrine tumor of the cervix may improve survival.

LCC15-MB: a vimentin-positive human breast cancer cell line from a femoral bone metastasis.

The LCC15-MB cell line was established from a femoral bone metastasis that arose in a 29-year-old woman initially diagnosed with an infiltrating ductal mammary adenocarcinoma. The tumor had a relatively high (8%) S-phase fraction and 1/23 positive lymph nodes (LN). Both the primary tumor and LN metastasis were positive for estrogen receptor (ER) and progesterone receptor (PgR), but lacked erbB2 expression. Approximately one year later, the patient presented with a 0.8 cm comedo-type intraductal mammary adenocarcinoma in the left breast that was negative for ER and PgR, but positive for erbB2. Thirty-five months after the initial diagnosis she was treated for acute skeletal metastasis, and stabilized with a hip replacement. At this time, tumor cells were removed from surplus involved bone, inoculated into cell culture, and developed into the LCC 15-MB cell line. The bone metastasis was a poorly differentiated adenocarcinoma lacking ER, PgR, and erbB2, characteristics shared by the LCC15-MB cells, although ER can be re-expressed by treatment of the LCC15-MB cells for 5 days with 75 microM 5-aza-2'-deoxycytidine. The LCC15-MB cell line is tumorigenic when implanted subcutaneously in NCr nu/nu mice and produces long-bone metastases after intracardiac injection. Although the bone metastasis from which the LCC15-MB cell line was derived lacked vimentin (VIM) expression, the original primary tumor and lymph node metastasis were strongly VIM positive, as are LCC15-MB cells in vitro and in nude mice. The karyotype and isozyme profiles of LCC15-MB cells are consistent with its origin from a human female, with most chromosome counts in the hypertriploid range. Thirty-two marker chromosomes are present. These cells provide an in vitro/in vivo model in which to study the inter-relationships between ER, VIM, and bone metastasis in human breast cancer.

Immunostaining of human melanomas by a monoclonal antibody to B700 mouse melanoma antigen.

Previous studies have shown that B700, an albumin-like murine melanoma antigen, has a human homologue termed H700. Polyclonal antibodies to B700 also bind to all cultured human, swine and hamster melanoma cells, suggesting that B700 is a "pan-melanoma" antigen. The objects of this investigation were: (a) to determine if 2-3-3, a monoclonal antibody to B700, can be used to identify human melanomas in formalin-fixed, paraffin-embedded tissues, and (b) to determine the specificity and potential diagnostic value of 2-3-3. Forty-eight of the 49 human melanomas, including spindle melanoma cells, stained positively, as did five of the eight pigmented naevi including cellular spindle naevi. Twenty-six of the 32 human non-melanomatous lesions were negative for 2-3-3 staining (weakly positive on one breast carcinoma and positive on five neural tumours). These results indicate that 2-3-3, a monoclonal antibody to the mouse melanoma antigen B700, can be used to identify H700 in archival specimens. 2-3-3 may have an advantage over HMB45, which is the most commonly used antibody for melanoma diagnosis, because of its immunoreactivity with spindle melanocytic lesions. Antibodies to B700 may prove to be a useful adjunct in the diagnosis of human melanoma and related lesions.

Intravascular and sclerosing bronchioloalveolar tumor. A pulmonary sarcoma of probable vascular origin.

A case of intravascular and sclerosing bronchioloalveolar tumor (IVSBAT) studied by light microscopy and electron microscopy is reported. Light microscopy revealed typical nodules composed of plump tumor cells in the peripheral regions and central areas of hyalinization. Histochemical examination revealed that the matrix material contained hyaluronic acid. Around the periphery of the nodules, tumor cells and matrix material were observed within the alveolar walls. Tumor was also present in numerous small bood vessels and lymphatics. Electron microscopy demonstrated that the tumor cells were polygonal or elongated and were connected by small junctions. The cytoplasm was filled with fine filaments, and dense bodies typical of those seen in smooth muscle cells were occasionally observed. Pinocytotic vesicles and basement membranes were also present. Some cells formed vessel-like lumina. Rows of tumor cells were identified within alveolar walls where they at first proliferated without disturbing the overall architecture; increasing numbers of tumor cells and matrix material gradually widened the alveolar walls, and the tumor finally expanded into the alveolar spaces. The ultrastructural features of the tumor cells are consistent with an origin form pericytes or endothelial cells; we suggest that IVSBAT is actually a sarcoma of vasoformative cells which arises within the alveolar walls, perhaps in multicentric fashion. We propose that the tumor be renamed "sclerosing interstitial vascular sarcoma".

Primary prostatic carcinoid tumor with intracytoplasmic prostatic acid phosphatase and prostate-specific antigen.

A case of prostatic carcinoid tumor with lymph node metastases is reported. The patient was a 78-year-old male who died in ventricular fibrillation. At autopsy, a 2 X 2 cm, white, irregular tumor was found in the prostate and there were several enlarged para-aortic lymph nodes. Both specimens contained a characteristic carcinoid tumor. Argyrophil stains revealed strong positivity in the primary as well as in the metastatic tumors. Electron micrographs prepared from formalin-fixed tissue demonstrated numerous membrane-bound dense-core granules. Immunoperoxidase-labeled antibodies against both prostatic acid phosphatase and prostate-specific antigen localized in the tumor cells. The ultrastructural and immunohistochemical results support differentiation of the tumor cells toward both prostatic epithelial cells and endocrine cells. We believe that this is the first reported case of a prostatic carcinoid tumor in which specific prostatic tissue markers have been demonstrated in the tumor cells.

Prostatic acid phosphatase in carcinoid tumors. Immunohistochemical and immunoblot studies.

The immunohistochemical demonstration of prostatic acid phosphatase (PAcP) and/or prostate-specific antigen (PSA) has been accepted as being reliable in identifying metastatic adenocarcinoma of prostate origin. However, islet cell tumors, especially hindgut-derived carcinoid tumors, have occasionally been reported to be positive for PAcP. We therefore studied a series of carcinoid tumors of the lung and gastrointestinal tract immunohistochemically for PAcP expression by using two polyclonal antibodies and one monoclonal antibody. Thirty-three carcinoid tumors were examined. All five rectal carcinoids in the series showed convincing PAcP positivity with at least two of the three anti-PAcP antibodies. No significant PAcP positivity was observed in the remaining 28 foregut- and midgut-derived carcinoid tumors, except for weak focal positivity in one lung carcinoid. PSA antibody reacted negatively in all cases. Western blots of an aqueous cell lysate from one rectal carcinoid revealed protein bands in the region of 45-55 kd that immunoreacted with anti-PAcP antibodies, confirming the validity of the immunostains. These results suggest that PAcP positivity is common in rectal carcinoid tumors and that it most likely represents true PAcP expression. This seemingly aberrant protein expression may be explained by the shared cloacal derivation of the rectum and prostate, giving rise to cells with both endocrine and partial prostatic epithelial differentiation.

Atypical and malignant neoplasms showing lipomatous differentiation. A study of 111 cases.

One-hundred-eleven cases of histopathologically atypical or malignant lipomatous lesions in the somatic soft tissue and retroperitoneum were studied. These consisted of 48 differentiated fatty neoplasms of the somatic soft tissues (DFT-S), 21 fatty neoplasms of the retroperitoneum (DFT-R), 33 myxoid liposarcomas from various sites and nine pleomorphic liposarcomas. DFT-S were defined as lipomatous lesions composed of mature fat and containing atypical stromal cells or lipoblasts. In the somatic soft tissues, this group included lesions that would be classified using published criteria as "atypical lipoma", "pleomorphic lipoma", "well-differentiated lipoma-like liposarcoma", and "sclerosing liposarcoma". All of the DFT-R met previously published criteria for "well differentiated liposarcoma" or "sclerosing liposarcoma". We found no consistent histologic differences between the DFT-S and DRT-R. No pure "round cell" liposarcomas were encountered although many myxoid liposarcomas had "round cell" areas. Follow-up data were available in 80 cases (72%) with a mean follow-up period of over 7 years. Among the DFT-S there were no uncontrollable recurrences, distant metastases, or tumor-related deaths. The depth of the neoplasm correlated with the tendency for local recurrence; no neoplasms primary in the subcutis recurred; 29% of the tumors recurred when they originated in the deep soft tissues or within the muscle. None of the recurrent tumors demonstrated "dedifferentiation." DFT-R had a recurrence rate of 67% and, although there were no distant metastases, nine patients (43%) died of tumor. Five retroperitoneal tumors dedifferentiated but did not metastasize. In light of this experience, we believe that the term "atypical lipoma" is warranted for the DFT-S and "well differentiated liposarcoma" is an appropriate label for the DFT-R. The overall mean survival for the 52 cases of liposarcoma (excluding DFT-S) was 13.6 years. The mean survival in "well differentiated liposarcoma" (11.25 years) was between that for myxoid liposarcoma (16.25 years) and that for pleomorphic liposarcoma (7 years). Six patients (29%) with myxoid liposarcoma developed local recurrences and 6 patients (29%) developed distant metastases and died. Metastasis was always associated with a round cell (or pleomorphic) component with increased numbers of mitotic figures in either the primary tumor or a local recurrence.

Intravascular large cell lymphoma coexisting within hemangiomas of the skin.

Intravascular lymphomatosis is a rare and peculiar subtype of large cell lymphoma. The authors present the pathologic, clinical, and radiologic findings of a patient with intravascular large cell lymphoma coexisting within hemangiomas of the skin. Initially the lymphoma was clinically confined to the hemangiomas and the patient was closely observed for disease progression. Within 10 months the patient developed disseminated lymphoma involving both adrenals. A clinical remission was achieved, but the patient soon relapsed, and despite further chemotherapy he died with disseminated disease 23 months after the initial diagnosis. This report presents the only known case of an intravascular large cell lymphoma coexisting within a vascular lesion and highlights the potential aggressive nature of intravascular lymphomas.

A novel biotinylated probe specific for hyaluronate. Its diagnostic value in diffuse malignant mesothelioma.

Diffuse malignant mesotheliomas are known to secrete a large amount of hyaluronate, whereas adenocarcinomas produce predominantly neutral mucins. In the present study, we assessed the diagnostic usefulness of a new, highly specific and sensitive hyaluronate binding probe to discriminate between mesotheliomas and adenocarcinomas. We studied 33 mesotheliomas and 37 adenocarcinomas in order to establish specific diagnostic criteria for using the hyaluronate binding probe. Of the adenocarcinomas, only three showed significant positive staining for hyaluronate (8%). By contrast, all the mesotheliomas exhibited positive staining for hyaluronate. Furthermore, the staining reaction was classed as moderate or greater in 26 mesotheliomas (79%), thus suggesting the utility of this probe in the differential diagnosis of malignant mesothelioma versus adenocarcinoma. We conclude that strong cytoplasmic or membranous staining for hyaluronate is highly predictive of malignant mesothelioma. The hyaluronate binding probe should therefore be considered an important adjunct to be used in combination with electron microscopy and immunohistochemistry in the histologic diagnosis of diffuse malignant mesothelioma.

Undifferentiated (embryonal) sarcoma of the liver. Clinical and pathologic study of 16 cases with emphasis on immunohistochemical features.

Undifferentiated (embryonal) sarcoma of the liver is a primitive mesenchymal neoplasm with predilection for individuals in the first 2 decades of life. In this study (10 boys, 6 girls), children in the age range of 6-10 years were most commonly affected (63%). Clinical features most frequently noted on presentation were abdominal pain or a palpable mass. In two cases there was cardiac involvement caused by invasion of the inferior vena cava with extension into the right atrium and ventricle; both children died of progressive dyspnea from tumor embolization to the lungs. One patient was a member of a kindred with the cancer family syndrome (Li-Fraumeni syndrome). There were 13 tumor-related deaths (86% mortality); on child was alive with recurrent tumor in the upper abdomen. Complete surgical resection was attempted in 10 of 15 children who underwent exploratory laparotomy; 2 were alive and well 1 and 5 years later, whereas 1 patient had a recurrence in the upper abdomen 3 years after diagnosis. Ultrastructural study (five cases) and immunohistochemistry (11 cases) supported a mesenchymal origin for the tumor, but failed to identify any diagnostic immunophenotype or specific line of differentiation. Coexpression of vimentin and cytokeratin was seen in three cases. Prompt detection of this aggressive tumor with complete surgical resection is the key to a successful outcome, but this is very difficult to achieve. Recent experience suggests that aggressive adjuvant chemotherapy may improve survival in some cases.

Primary leiomyosarcoma of adrenal gland. Case report with immunohistochemical and ultrastructural study.

A primary leiomyosarcoma of the right adrenal gland is reported in a 49-year-old male who presented with progressive flank pain. This is the second case in the English language literature and the first to have documentation of malignant behavior. The tumor measured 11 cm in diameter and showed marked necrosis with prominent mitotic activity (average 15 per 10 high-power fields). Smooth muscle differentiation was apparent ultrastructurally and confirmed by positive immunostaining for muscle-specific and alpha-smooth muscle actin. Bony metastases developed; following palliative treatment with radiation and chemotherapy, the patient is alive with tumor 9 months later. Origin from smooth muscle associated with the central adrenal vein or its tributaries is proposed.

Unique pulmonary presentation of an angiomyolipoma. Analysis of clinical, radiographic, and histopathologic features.

Extrarenal angiomyolipomas are rare lesions that have been described in the liver, hard palate, skin, uterus, vagina, penis, and spermatic cord. In this report we present the clinical, radiographic, and pathologic findings of an angiomyolipoma of the lung in a 68-year-old woman without tuberous sclerosis or lymphangioleiomyomatosis. To our knowledge, this report is the first description of pulmonary angiomyolipoma. Distinction from other benign and malignant pulmonary mesenchymal lesions depends on recognition of traditional histologic criteria. In contrast to renal angiomyolipomas, study of this case and review of prior reports reveals that extrarenal angiomyolipomas are most often well demarcated, easily resected, and not associated with tuberous sclerosis.