The trefoil gene family are coordinately expressed immediate-early genes: EGF receptor- and MAP kinase-dependent interregulation.

The trefoil gene family of mucus cell-secreted proteins is a critical mediator of gastrointestinal mucosal restitution. Transcription of trefoil genes is induced during mucosal repair, but the regulatory mechanisms involved are unknown. Mice deficient in the intestine-specific peptide intestinal trefoil factor (ITF), in which colonic restitution is lethally impaired, showed reduced expression of the gastric trefoil genes SP and pS2, suggesting that trefoil peptides may individually regulate transcription of the entire family. In gastric cell lines, the trefoils were shown to act in a manner suggestive of immediate-early genes capable of auto- and cross-induction through cis-acting regulatory regions. Trefoil-mediated transcriptional regulation required activation of the Ras/MEK/MAP kinase signal transduction pathway. EGF receptor (EGF-R) activation was also necessary for trefoil auto- and cross-induction, and both spasmolytic polypeptide (SP) and ITF stimulation of gastric cell lines led to phosphorylation of EGF-R. Nevertheless, ITF and ITF-thioredoxin cell surface binding at 4 degrees C colocalized not with EGF-R, but with CD71, which is found in clathrin-coated pits, suggesting that integration of trefoil peptide responses may occur after internalization. As EGF-R expression is itself strongly induced after mucosal damage, the trefoil/EGF-R relationship may be pivotal in the generation and maintenance of the mucosal repair phenotype.

Trefoil peptides promote epithelial migration through a transforming growth factor beta-independent pathway.

The trefoil peptides, a recently recognized family of protease-resistant peptides, expressed in a regional specific pattern throughout the normal gastrointestinal tract. Although these peptides have been hypothesized to act as growth factors, their functional properties are largely unknown. Addition of recombinant trefoil peptides human spasmolytic polypeptide (HSP), rat and human intestinal trefoil factor (RITF and HITF) to subconfluent nontransformed rat intestinal epithelial cell lines (IEC-6 and IEC-17), human colon cancer-derived cell lines (HT-29 and CaCO2) or nontransformed fibroblasts (NRK and BHK) had no significant effect on proliferation. However addition of the trefoil peptides to wounded monolayers of confluent IEC-6 cells in an in vitro model of epithelial restitution resulted in a 3-6-fold increase in the rate of epithelial migration into the wound. Stimulation of restitution by the trefoil peptide HSP was enhanced in a cooperative fashion by the addition of mucin glycoproteins purified from the colon or small intestine of either rat or man, achieving up to a 15-fold enhancement in restitution. No synergistic effect was observed by the addition of nonmucin glycoproteins. In contrast to cytokine stimulation of intestinal epithelial cell restitution which is mediated through enhanced TGF beta bioactivity, trefoil peptide, and trefoil peptide-mucin glycoprotein stimulation of restitution was not associated with alteration in concentrations of bioactive TGF-beta and was not affected by the presence of immunoneutralizing anti-TGF beta antiserum. Collectively, these findings suggest that the trefoil peptides which are secreted onto the lumenal surface of the gastrointestinal tract may act in conjunction with the mucin glycoprotein products of goblet cells to promote reestablishment of mucosal integrity after injury through mechanisms distinct from those which may act at the basolateral pole of the epithelium.

Evidence that loss of chromosome 18q is associated with tumor progression.

Four sets of cell lines (UM-SCC-14A, -14B, and -14C; UM-SCC-17A and -17B; UM-SCC-81A and -81B; and UM-SCC-83A and -83B), established from primary and metastatic or locally recurrent tumors from four patients with squamous cell carcinoma of the head and neck, were examined for loss of heterozygosity (LOH) on chromosome 18q. Metastatic or recurrent cell lines from all four exhibited 18q LOH. UM-SCC-14A, -14B, and -14C, which were derived from locally recurrent (14A and 14B) and metastatic (14C) tumors, lost all of 18q. However, in the other three cases, there was a partial loss of 18q in the recurrent or metastatic tumor cell lines but not in the primary tumor cell lines from the same patient. To determine whether the cell lines accurately reflect in vivo loss of 18q, we analyzed matched sets of normal, tumor, and tumor cell line DNA from eight patients with squamous cell carcinoma of the head and neck, including the tumor tissue corresponding to UM-SCC-81B. Three of the additional seven tumors and cell lines had 18q LOH. For all eight cases in which tumor and corresponding cell line DNAs were analyzed, there was complete concordance between allelic loss in the tumor and allelic loss in the corresponding cell line. The common region of loss established by tumors and cell lines with partial loss includes 18q21-18qter. This region contains the putative tumor suppressor gene DCC and two Mad (Mothers against dpp)-related genes, DPC4 and MADR2, which are both components in a transforming growth factor-beta-like signaling pathway. Loss of 18q in metastatic and locally recurrent tumors, but not in primary tumors from the same patients, suggests that a tumor suppressor gene in this region may be important in the progression of squamous cell carcinoma.

Sarcoidosis presenting as a tumorlike muscular lesion. Case report and review of the literature.

Sarcoid myopathy presenting as a tumorlike lesion is an exceedingly rare presentation of sarcoidosis. Concurrent extramuscular involvement is common. Chest radiographs, if abnormal, may suggest the diagnosis. Magnetic resonance imaging is the preferred study for diagnosis and follow-up of tumorous sarcoid myopathy. Optimal therapy is not clear. Favorable responses have been cited with surgery or corticosteroids (alone or in combination). Azathioprine or alternative immunosuppressive agents (for example, antimalarials or methotrexate) may have a role in corticosteroid-recalcitrant patients. The role of local radiotherapy is controversial and should be reserved for severe localized disease refractory to aggressive medical therapy.

Hepatobiliary cystadenoma and cystadenocarcinoma. A light microscopic and immunohistochemical study of 70 patients.

Fifty-two hepatobiliary cystadenomas and 18 hepatobiliary cystadenocarcinomas were drawn from the files of the Armed Forces Institute of Pathology and Rhode Island Hospital and studied in an attempt to correlate light microscopic features of the tumors with immunohistochemical and follow-up data. The cystadenoma patients ranged in age from 2 to 87 years at the time of initial diagnosis (mean, 45 years). All the cystadenomas were multilocular with benign cuboidal to columnar epithelium, and 44 (85%) had densely cellular spindle cell ("ovarian-like") stromata; 96% were female. Fifty-one cystadenomas were macrocystic lesions, typically lined by mucinous epithelium; one of the benign lesions was a serous cystadenoma (microcystic adenoma) reminiscent of the more commonly encountered pancreatic lesion of the same name. The cystadenocarcinoma patients ranged in age from 24 to 90 years at the time of first diagnosis (mean, 59 years); eight patients (44%) were male. All but one of the lesions were multilocular with malignant in situ (one case) or invasive tubulopapillary (15 cases), solid (one case), or adenosquamous (one case) epithelial components. Areas of preexisting benign cystadenoma were found in six (33%), an observation suggesting that benign lesions may evolve into malignant ones in some patients. Most cystadenomas and cystadenocarcinomas arose in the liver, a few in the extrahepatic biliary system (including the gallbladder). On follow-up, the cystadenoma patients in general were successfully treated by surgical excision of the lesions in toto; patients treated by subtotal resection often had persistent symptomatic disease. Four cystadenocarcinoma patients died of their tumors; another two patients were alive with persistent disease at last follow-up. In both the benign and the malignant lesions, most tumor cells were positive on immunohistochemical staining with antibodies to cytokeratin, epithelial membrane antigen, and carcinoembryonic antigen; scattered chromogranin-positive cells also appeared in a few tumors of both types. Immunohistochemistry did not yield a diagnostic immunoprofile to distinguish cystadenoma from cystadenocarcinoma or from other epithelial lesions arising within the abdominal cavity. At least two types of cystadenocarcinoma exist, one developing exclusively in female patients, usually accompanied by an "ovarian-like" stroma, which follows an indolent course; and the other, lacking the distinctive cellular stroma, seen in males, follows a more aggressive course and is more likely to result in the patient's death from tumor. It remains an open question whether the cystadenocarcinomas lacking a mesenchymal stroma, which arise in women, will follow the same aggressive course as similar lesions arising in men.

Lipomatous hemangiopericytoma: a rare variant of hemangiopericytoma that may be confused with liposarcoma.

We describe the clinicopathologic features and biologic behavior of 16 cases of histologically benign hemangiopericytoma containing a variable amount of mature fat as an intrinsic part of the neoplasm. These so-called lipomatous hemangiopericytomas occurred primarily in men (12 men and 4 women) with a mean age of 54 years (range, 33-74 years). All occurred in deep soft tissue and had an average size of 10 cm when first detected. All were characterized by a relatively sharp border and typical histologic features of hemangiopericytomas, including oval to round cells surrounding a sinusoidal and staghorn vasculature often with perivascular hyalinization. Mature fat varied in amount but usually occupied approximately one quarter to three quarters of the area of tumor. Mitotic activity was low, with more than half the cases having no mitotic activity. Five cases showed moderate nuclear atypia. In four cases, the pericytic regions had sclerotic zones. In contrast to liposarcoma, neither lipoblasts nor isolated atypical hyperchromatic cells within mature fat, as are seen in well-differentiated liposarcoma, were present. Immunohistochemistry performed in four cases showed factor XIIIa in tumor cells and an intricate pattern of immunoreactivity around cells for type IV collagen. CD34 and smooth-muscle actins were identified in two of four cases. Follow-up in seven cases showed no recurrences or metastases within the follow-up period of 1 to 7 years. Because these lesions are located in deep soft tissue and contain large amounts of mature fat, they could be mistaken for well-differentiated liposarcomas in limited biopsy material, although the distinction is easily made in examining the entire specimen. The lipomatous hemangiopericytoma represents yet another example of a bimodal mesenchymal tumor containing mature fat and raises the question of whether a common cytogenetic abnormality can explain the emergence of two clonal populations in this hybrid tumor.

Cortical osteofibrous dysplasia of long bone and its relationship to adamantinoma. A clinicopathologic study of 30 cases.

Thirty cases of cortical osteofibrous dysplasia (COFD) were studied in an attempt at defining the relationship of COFD to adamantinoma. The patients ranged in age from newborn to 39 years (mean 13.4 years). The male:female ratio was 1:1. Presenting symptoms were most often pain or a mass. The tibia was involved in all 30 patients; in addition, the ipsilateral fibula was involved in five patients (17%). The histologic appearance of the lesions was dominated by the combination of woven bone trabeculae with prominent osteoblastic rimming and a loose, slightly myxoid stroma (less heavily collagenized in most instances than usually encountered in intramedullary fibrous dysplasia). Results of immunohistochemical study showed isolated cytokeratin-positive cells in the stroma of 28 of the lesions (93%). However, hyperchromatic epithelial islands characteristic of adamantinoma were not found in any of the 30 cases. A control population of 50 fibro-osseous lesions (intramedullary fibrous dysplasia, sclerosing fibroxanthoma, and cranial ossifying fibroma) was studied immunohistochemically; in none of these control cases were cytokeratin-positive cells found. Follow-up data were obtained in 17 cases (57%); the period ranged from 1 to 16 years (mean 6.05 years). Certain overlapping clinical features (including the location of the vast majority of the lesions in the tibia and, less often, the fibula) and the morphologic similarities of many areas of COFD and adamantinoma (particularly the shared presence of cytokeratin-positive cells) suggest a more than coincidental association between COFD and a adamantinoma. However, to date none of the 30 cases of COFD evaluated in this study has developed an adamantinoma.

Multiple spindle cell lipomas: a report of 7 familial and 11 nonfamilial cases.

Spindle cell lipoma, a variant of a benign lipoma, usually occurs as a solitary, subcutaneous, circumscribed lesion in the posterior back, neck, or shoulders of older men. Multiple lesions are exceedingly rare. To our knowledge, there have been no previous series reported of patients with multiple subcutaneous spindle cell lipomas. We examine the clinicopathologic findings of a group of patients with multiple spindle cell lipomas, including seven with a familial occurrence of this disease. The Soft Tissue Registry of the Armed Forces Institute of Pathology and the consultation files of one of the authors (S.W.W.) from the Department of Pathology at the University of Michigan were searched for patients with multiple spindle cell lipomas. All patients' records, clinical history, and pathology were reviewed. All patients had a minimum of two tumors that met strict morphologic criteria for spindle cell lipoma. Pleomorphic cells, typical of pleomorphic lipoma, were observed in some cases and were acceptable as part of the spectrum of spindle cell lipomas. Associated lesions, family history, ethnic background, daily habits, and natural progression of disease were recorded and compared. Eighteen patients in our files met the criteria for multiple spindle cell lipomas; 4 of the 18 patients were from the same family. Three additional patients had a family history of multiple spindle cell lipomas. The ratio of patients with multiple spindle cell lipomas to all patients with spindle cell lipoma in the two consultation files was 0.5 and 3%, respectively. All of the patients in our study were male; three had a family history of females with less severe disease (fewer and smaller spindle cell lipomas); however, no material from these female patients was available for review. All but four patients presented in their sixth through eighth decades of life; yet, several older patients stated that their first lesion occurred in their fifth decade. Patients had between 2 and >220 lesions, which usually commenced on the posterior neck or back, commonly followed by additional bilateral lesions on the shoulders and upper torso. The natural history of this disease revealed development of multicentric lesions over several years, for both familial and nonfamilial cases. The tumors became more cellular as the disease progressed, often with features of pleomorphic lipoma; however, no patients developed spindle cell liposarcoma. Multiple spindle cell lipomas are rare. The clinical presentation may mimic Madelung's disease (symmetrical lipomatosis). As mentioned above, some cases are familial. Genetic predisposition must be further examined. There appears to be no common ethnic background, environmental exposure, medical condition, or syndrome of associated lesions with multiple spindle cell lipomas.

Interpretation of head and neck biopsies in Wegener's granulomatosis. A pathologic study of 126 biopsies in 70 patients.

The majority of patients with classic Wegener's granulomatosis present with symptoms of head and neck disease; accordingly, accurate interpretation of biopsy specimens from these sites is essential. This report details the histologic findings in 126 head and neck biopsy specimens from 70 patients (36 male and 34 female). Tissues were obtained from the following sites: 60 nasal, 27 paranasal sinuses, 17 laryngeal, five periorbital, five oral, four middle ear, three mastoid, two external ear, and three salivary gland. Vasculitis, necrosis, and granulomatous inflammation together were seen in only 16% of all head and neck biopsy specimens. Both vasculitis and granulomatous inflammation were seen in 21% and vasculitis and necrosis in 23% of the biopsy specimens reviewed. We discuss the problems in differential diagnosis, particularly the importance of excluding granulomatous infectious processes, which can imitate the histopathologic features of Wegener's granulomatosis. Based on this study, we propose criteria for the diagnosis of Wegener's granulomatosis based on biopsy specimens from the head and neck region.

Hepatic sarcoidosis. Clinicopathologic features in 100 patients.

The patterns of hepatic injury were studied in 100 patients with a diagnosis of sarcoidosis and clinical evidence of liver disease that led to diagnostic liver biopsy. Granulomas were present in all patients; they occupied from < 1% to > 90% of the total volume of tissue examined and were most often located in the portal/periportal region. In none of the 100 cases were infectious organisms identified by special stains, culture, or serology. In 99% of cases, these granulomas were noncaseating; in one of the 100 cases central caseation was noted. In addition to the granulomas present in all biopsies, three broad categories of histologic change were found: cholestatic (58%), necroinflammatory (41%), and vascular (20%). Among those with cholestasis, 19 patients had bile duct lesions similar to primary biliary cirrhosis, whereas another 13 had a pattern of periductal fibrosis reminiscent of primary sclerosing cholangitis. In 37 patients with chronic cholestasis, a decrease in the number of bile ducts (ductopenia) was noted. Twelve patients had an acute cholangitis suggestive of mechanical obstruction--although no clinical evidence of ductal obstruction was found. Necroinflammatory changes included spotty necrosis suggesting hepatitis of diverse etiologies (including viral infection and drug reaction) and chronic portal inflammation suggestive of chronic active hepatitis. Vascular changes consisted of sinusoidal dilatation (14 cases) and nodular regenerative hyperplasia (9 cases). In 6% of the patients, the only changes in the biopsy were those of granulomatous inflammation; each of these patients had a dominant mass ("sarcoidoma"), which had been biopsied to rule out tumor. Fibrosis was seen in 21% of the biopsies--periportal (13%), bridging (2%), or cirrhosis (6%). It is clear that sarcoidosis can cause progressive liver disease with a wide array of histologic features that can mimic those of other primary liver diseases.

Synovial hemangioma: a report of 20 cases with differential diagnostic considerations.

True synovial-based hemangiomas are uncommon lesions and, as such, may enter the differential diagnosis of other lesions encountered more frequently in clinical practice, including pigmented villonodular synovitis and traumatic hemarthrosis. The consultation files of the Armed Forces Institute of Pathology were searched for benign vascular lesions diagnosed as synovial or bursal hemangiomas vascular lesions diagnosed as synovial or bursal hemangiomas submitted between the years 1960 and 1985; 20 cases of synovial hemangioma were identified. The patients ranged in age from 9 to 49 years at the time of presentation (average age, 25 years). Sixty-five percent of the patients were male; 35% were female. Presenting symptoms included pain and swelling (31%), pain alone (31%), and a painless mass (31%). Affected regions included the knee (60%), the elbow (30%), and the finger (10%). In 65% of cases the lesion was confined to the intra-articular synovium; in 30% of cases the hemangioma was located in a bursa adjacent to a joint. One case was located largely within the joint cavity but had an area of extension into the suprapatellar recess. The dominant histologic patterns included cavernous hemangioma (50%), lobular capillary hemangioma (25%), arteriovenous hemangioma (20%), and venous hemangioma (5%). One lesion (which had been incompletely excised) was removed in its entirety 3 months after the initial subtotal resection; otherwise, none of the patients studied developed recurrent disease. The clinical diagnosis of hemangioma was made in 22% of cases, while an initial pathologic diagnosis of hemangioma was reached in 67% of cases. Pathologic differential diagnostic considerations include nonspecific synovitis/bursitis, pigmented villonodular synovitis, nodular synovitis, and organizing hemorrhage. A relationship between synovial hemangioma and pigmented villonodular synovitis was not suggested by this analysis of our material.

Small cell osteosarcoma of bone: an immunohistochemical study with differential diagnostic considerations.

Seventy-nine cases of small round cell tumors involving bone were studied in an attempt to learn whether the immunohistochemical features of the lesions might allow distinction of small cell osteosarcoma from other potential differential diagnostic considerations, including Ewing's sarcoma, atypical Ewing's sarcoma, primitive neuroectodermal tumor, mesenchymal chondrosarcoma, lymphoma, and the Askin tumor. The tissues studied were all formalin-fixed, decalcified, paraffin sections from patients between the ages of 16 and 48 years. With one exception (a small cell osteosarcoma), none of the lesions was cytokeratin positive. Moreover, none of the lesions was epithelial membrane antigen, desmin, factor VIII-related antigen, synaptophysin, or Leu-M1 positive. Accordingly, strong positivity for these antibodies in a majority of tumor cells should prompt inclusion of tumor types other than those listed above in the differential diagnosis. Vimentin positivity was seen in a majority of the tumors studied irrespective of histologic type. Scattered tumor cells (< 25%) showed positivity with antibodies to muscle-specific actin and smooth muscle actin in several of the different tumor types studied. No lesions other than lymphoma were leukocyte-common antigen (LCA) positive; all but two lymphomas were LCA positive, while all but one lymphoma were L26 positive. One (lymphoblastic) lymphoma was LCA and L26 negative. S-100, neuron-specific enolase, and Leu-7 did not prove to be specific for "neural-associated" tumors, but rather appeared in some small cell osteosarcomas, Ewing's sarcomas, atypical Ewing's sarcomas, primitive neuroectodermal tumors, mesenchymal chondrosarcomas, lymphomas, and Askin tumors. Antibody to cell surface antigen HBA71 was positive in three Ewing's sarcomas (two typical and one atypical) and negative in small cell osteosarcoma (three cases), mesenchymal chondrosarcoma (two cases), and lymphoma (one case). While some guidance may be derived from analysis of immunohistochemical staining patterns in a given lesion, the results reported in the present study do not suggest that routine immunohistochemistry alone will permit distinction of these small cell tumors of bone from one another. The value of immunohistochemical studies appears to lie particularly in the use of antibodies to LCA and S-100 protein to distinguish lymphoma and mesenchymal chondrosarcoma, and perhaps antibody to HBA71 to distinguish neural family lesions (such as Ewing's sarcoma), from other small cell tumors, such as small cell osteosarcoma.

Lymphoid pneumonitis in 50 adult patients infected with the human immunodeficiency virus: lymphocytic interstitial pneumonitis versus nonspecific interstitial pneumonitis.

Lymphocytic interstitial pneumonitis (LIP) and nonspecific interstitial pneumonitis (NIP) are pulmonary complications of human immunodeficiency virus (HIV) infection that occur in the absence of a detectable opportunistic infection or neoplasm. We reviewed lung biopsy specimens from 50 adult HIV-infected patients, of whom four had LIP and 46 had NIP. The majority (47 of 50) of specimens from patients with NIP showed mild chronic interstitial pneumonitis (CIP/NIP), with three showing features of diffuse alveolar damage, organizing phase. In contrast to CIP/NIP, the five specimens from four patients with LIP demonstrated more extensive lymphocytic interstitial infiltrates that extended into the alveolar septal interstitium. The majority of the interstitial lymphocytes in both NIP and LIP were of T-cell origin and stained for UCHL-1. The etiologies of NIP and LIP remain unknown. Since the common opportunistic infections were excluded by routine methods, we sought, with special techniques, to investigate whether HIV, Epstein-Barr virus (EBV), or cytomegalovirus (CMV) could be identified in lung biopsy specimens from these patients. By in situ hybridization, we found one LIP specimen with expression of large amounts of HIV RNA primarily within macrophages in germinal centers; in the remaining specimens, occasional cells expressing HIV RNA were found (two LIP and four NIP). Neither CMV nor EBV was found by in situ hybridization in seven specimens; in these same specimens EBV was detected using the polymerase chain reaction in only one case of NIP, similar to results in control specimens. These results, together with the knowledge that lymphocytic pulmonary lesions may be caused by lentiviruses in humans and animals, suggest that HIV plays a significant role in the pathogenesis of both NIP and LIP in adult HIV-infected patients; in contrast, our data do not demonstrate a direct role for either EBV or CMV.

The surgical pathology of gastrointestinal Hodgkin's disease.

The files of the National Cancer Institute were searched for all surgical specimens from the gastrointestinal (GI) tract with the diagnosis of Hodgkin's disease (HD) that were accessioned during the years 1953-1990; six patients with a histologically reconfirmed diagnosis were identified. Of these patients, four presented with GI HD and two had recurrent HD. Primary HD appeared in the stomach (three patients) and the duodenum (one patient); recurrent HD after diagnosis in a conventional nodal site appeared in the stomach (one patient) and the colon (one patient). One of the cases of primary gastric disease was a composite lymphoma consisting of HD and diffuse large cell lymphoma. In view of the rarity of GI tract involvement by HD, a diagnosis of primary GI HD should be viewed with skepticism; support for such a diagnosis may be provided by both classic histopathologic features of HD and immunostaining, but no single feature can be regarded as pathognomonic.

Chemotherapy and P-glycoprotein expression in chondrosarcoma.

Chondrosarcomas are alleged to be resistant to chemotherapy. A retrospective review of our experience primarily with dedifferentiated chondrosarcomas treated with chemotherapy was performed to reevaluate the efficacy of chemotherapy for this tumor. There were 18 patients: 14 stage IIB and four stage III. Seventeen patients had dedifferentiated chondrosarcoma. The median age at diagnosis was 57 years. Fourteen of the patients underwent wide excision of the tumor, two underwent amputation, and two had no surgery. The femur and the pelvis were the most common locations of the primary tumor. Chemotherapy for 11 of the patients consisted of cisplatin and doxorubicin. Survival was analyzed with the Kaplan-Meier method; the median survival was 12 months. The hypothesis that chondrosarcomas express P-glycoprotein was tested. Expression of P-glycoprotein was evaluated by immunostaining with use of the C494 and C219 antibodies on 41 benign and malignant cartilage tumors, six of which were from the patients in the chemotherapy group. Immunostaining revealed that 37 of 41 cartilage tumors expressed P-glycoprotein. The rate of survival of patients with high-grade chondrosarcoma treated with chemotherapy is poor. P-glycoprotein expression is common in benign and malignant cartilage lesions. The lack of response to chemotherapy may be related to the expression of P-glycoprotein.

Giant cell tumor of the thoracic spine: MR appearance.

The MR features of a giant cell tumor that predominantly involved the posterior elements of a thoracic vertebra are presented. This extradural neoplasm compressed and displaced the spinal cord. The tumor had low to intermediate signal on short-repetition-time images and predominantly high signal on long-repetition-time images. It showed mild heterogeneous enhancement with gadopentetate dimeglumine.

Skeletal-extraskeletal angiomatosis. A clinicopathological study of fourteen patients and nosologic considerations.

We reviewed the consultation files of the ARmed Forces Institute of Pathology for 1951 through 1989 and identified fourteen patients who had had skeletal-extraskeletal angiomatosis. Skeletal-extraskeletal angiomatosis was defined as a benign vascular proliferation involving the medullary cavity of bone and at least one other type of tissue. The age of the patients at the time of initial biopsy ranged from nine months to sixty-nine years (average, twenty-two years; median, ten years). Ten of the patients were male and four were female. The presenting signs and symptoms were highly variable; they included pain (four patients), a mass noted at birth (three patients), a painless mass that developed after birth (two patients), both pain and a mass (one patient), a localized deformity of the thoracic spine (one patient), and anemia associated with chronic bleeding of the gastrointestinal tract (one patient); in this last patient, skeletal lesions subsequently were found and biopsied. Skeletal-extraskeletal angiomatosis was an incidental finding in the remaining two patients. Multiple bones were involved in thirteen of the fourteen patients. Histologically, three patterns of lesion could be identified: cavernous lymphangioma (six patients), cavernous hemangioma (six patients), and arteriovenous hemangioma (two patients). Five of the patients died (three of sepsis associated with persistent lesions of angiomatosis and two of unrelated causes); eight of the patients survived but had residual disease, and one survived and had no evidence of residual disease.

Pediatric myofibromatosis of the head and neck.

OBJECTIVES: To examine the clinical and pathological features of pediatric myofibroma of the head and neck and to discuss the challenges in diagnosis and treatment. DESIGN: A retrospective search of pathology department and clinical records to identify patients with myofibroma and a retrospective review of English-language medical publications. SETTING: Academic medical center. PATIENTS: Thirteen pediatric patients (aged from birth to 8 years old) diagnosed as having myofibroma of the head and neck. RESULTS: Nine of 13 patients were cured with conservative surgical excision. Four patients (31%) had recurrence, requiring multiple surgical procedures. One third showed spontaneous regression clinically or by histological examination. The clinical course did not parallel the histological appearance, as high cellularity and mitotic figures were commonplace among the specimens. A misdiagnosis of malignancy was not unusual in this series, as 3 patients had an initial diagnosis of fibrosarcoma, which on review was revised to myofibroma. CONCLUSIONS: Myofibromatosis is a distinct disorder among the great number of fibrous proliferations occurring in infants and children, with a particular predilection for the head and neck region. These lesions should be clearly distinguished from conventional adult-type fibromatoses (desmoid tumors), which are more aggressive. Most patients have solitary lesions that respond well to conservative surgical excision, whereas a few of these lesions behave more aggressively, requiring several surgical procedures for the management of recurrent or persistent tumor. Many of these lesions show spontaneous regression, suggesting that lesions not affecting vital functions, resulting in growth anomalies, or demonstrating rapid aggressive growth may be managed conservatively.

Mucinous cystadenoma of the lung. A report of two cases with immunohistochemical and ultrastructural analysis.

We describe two patients who presented with solitary pulmonary masses that consisted of unilocular cysts lined by columnar mucinous epithelium. The cysts contained copious mucus. The epithelial lining of the cysts showed foci of stratification and papillary infolding. Histologically identical lesions have previously been termed unusual mucous cysts or mucinous cystadenomas. We believe that these tumors are true neoplasms differentiating toward the respiratory epithelial mucous cell. They should be distinguished from a variety of pulmonary neoplasms including bronchoalveolar carcinoma, bronchial mucous gland adenoma, mucoepidermoid carcinoma, and metastatic adenocarcinoma.

Squamous cell carcinoma of the buccal mucosa.

The purpose of this study was to establish treatment criteria for patients with early-stage squamous cell carcinoma of the buccal mucosa. Thirty-one patients were analyzed in a retrospective fashion. Distribution of patients according to tumor stage was relatively even. Within 5 years recurrent disease developed in nearly 80% of evaluable patients. There was a 100% overall incidence of local disease recurrence for patients with stage I and II tumors treated with wide local excision alone and followed up for more than 2 years. On the basis of these data, we conclude that wide local excision for early-stage buccal carcinoma is associated with a high local failure rate. Possible causes for failure and alternative treatment approaches are discussed.