Biomedical subjects

C M Coffin

Publications and source records attributed to C M Coffin.

At least 37 records · Page 2Linked to original sources

PubMed1998

Idiopathic fibrosclerotic disorders and other inflammatory pseudotumors.

Fibroinflammatory disorders constitute heterogeneous clinical conditions whose cause and pathogenesis are largely unknown. Inflammatory pseudotumor has been applied in a generic sense to several of these disorders, which present as a mass displacing surrounding anatomic structures or leading to organ dysfunction secondary to compressive growth around the ureter(s), common bile duct, or great vessels in the mediastinum. The fibrosclerosing disorders of retroperitoneal fibrosis, sclerosing mediastinitis, sclerosing cholangitis, orbital pseudotumor, and Riedel thyroiditis are seemingly related in a clinical sense because there are well-documented cases of patients with two or more of these conditions and reports of these disorders presenting in family members. Although the pathogenesis of the fibrosclerotic disorders has not been elucidated, autoimmunity in the context of an established collagen vascular disease or the setting of inflammatory periaortitis in retroperitoneal fibrosis has been one suggested mechanism. In the course of the diagnostic evaluation of an individual with a suspected fibrosclerotic disorder, it is imperative to exclude an underlying infection or malignancy. This caveat is especially relevant to sclerosing mediastinitis as a presentation of histoplasmosis or to retroperitoneal fibrosis secondary to a sclerosing large cell lymphoma. Sclerosing mesenteritis has some clinical and pathological overlap with the fibrosclerotic disorders, but its nosologic and pathogenetic relationship is uncertain at this time. There are several other fibroinflammatory processes, such as focal myositis, inflammatory fibroid polyp of the gastrointestinal tract, calcifying fibrous pseudotumor, and sclerosing peritonitis, which are probably unrelated to inflammatory myofibroblastic tumor or the primary fibrosclerotic disorders.

Granuloma, Plasma Cell↗

PubMed1997

Pathologic features of rhabdomyosarcoma before and after treatment: a clinicopathologic and immunohistochemical analysis.

Few studies have analyzed the relationship among pathology, therapy-induced changes, proliferative activity, and outcome for rhabdomyosarcoma (RMS), despite the challenges of histopathologic interpretation of this tumor after treatment. Although cytodifferentiation and decreased mitotic activity after treatment were documented previously, the clinical consequences of these changes are uncertain because of the small number of cases analyzed. We analyzed 16 RMSs with pre- and post-treatment specimens for clinicopathologic features, outcome, and immunohistochemical data on formalin-fixed, paraffin-embedded tissue for vimentin, smooth muscle actin, muscle-specific actin, desmin, myoglobin, p53 protein, topoisomerase II-alpha, and MIB-1 proliferative activity. Four of eight alveolar (ARMS), five of five botryoid (BRMS), and two of three nonbotryoid embryonal (ERMS) RMSs displayed varying degrees of post-therapeutic histologic maturation and expressed one or more myoid markers. The remaining five RMSs had no cytodifferentiation. Myoid marker expression did not change significantly. In BRMS, MIB-1 and topoisomerase II-alpha proliferative activity decreased after therapy and correlated with cytodifferentiation and survival. This relationship was less clear for ERMS and ARMS. Five nonbotryoid RMSs without cytodifferentiation had either unchanged or increased proliferative activity, and four of these patients died of RMS. Six nonbotryoid RMSs with both cytodifferentiation and residual foci of undifferentiated cells had variable outcomes, including longer survival. We conclude that BRMS and ERMS exhibit therapy-induced cytodifferentiation more frequently than does ARMS. Cytodifferentiation and decreased proliferative activity are associated with favorable outcome in BRMS; unchanged or increased post-therapeutic proliferative activity suggests aggressive biologic potential in ERMS and ARMS. Combined patterns of cytodifferentiation and residual undifferentiated foci might be associated with increased, decreased, or unchanged proliferative activity and are difficult to interpret, but the presence of cytodifferentiation might presage an improved survival. Immunohistochemical analysis for proliferation markers might be useful for highlighting foci of less differentiated RMS or cytodifferentiated tumor cells in contrast to non-neoplastic, terminally differentiated muscle cells.

Actins↗

PubMed1996

Aprosencephaly and cerebellar dysgenesis in sibs.

Aprosencephaly is a rare, lethal malformation sequence of the central nervous system that has been attributed to a postneuralation encephaloclastic process. We describe autopsy findings consistent with aprosencephaly in 2 fetuses conceived from a consanguineous mating (first cousins). Both showed anencephalic manifestations; however, the crania were intact, with fused sutures. The neuropathologic findings were essentially identical. Each fetus had complete absence of the telecephalon and pyramidal tracts, rudimentary diencephalic and mesencephalic structures, primitive cerebellar hemispheres, posterolateral clusters of primitive neural cells in the medullas suggesting an abnormality of neural migration, a normally-formed spinal cord, and retinal dysplasia within normally-formed globes. In addition, both fetuses manifested a peculiar perivascular mesenchymal proliferation seen only within the central nervous system. The similarity of these cases, coupled with parental consanguinity, suggests a primary malformation in brain development due to the homozygous representation of a mutant allele. We hypothesize that these patients may represent a defect in a gene important in brain development, the nature of which has yet to be elucidated.

Abnormalities, Multiple↗

PubMed1996

Colorectal adenocarcinoma as a second malignant neoplasm following Wilms' tumor and rhabdomyosarcoma.

Colorectal carcinoma is one of the most common primary malignancies in adults and occurs in older patients after pelvic radiation. It is rare in children and young adults. We report two cases of colonic adenocarcinoma which were second malignant neoplasms following treatment for early childhood malignancies. One child had Wilms' tumor at 9 months of age treated with preoperative radiation and surgery. He developed radiation colitis and multifocal intestinal adenocarcinomas 42 years later and died with abdominal carcinomatosis. The second child had retroperitoneal embryonal rhabdomyosarcoma at age 1 year and was treated with preoperative radiation, surgery, and chemotherapy. At age 2 years he had radiation colitis; at age 11 years he had rectal adenocarcinoma associated with adenomatous polyps, focal adenomatous change and radiation colitis. Immunohistochemical studies revealed p53 positivity in both adenocarcinomas and in adenomas from the second patient, suggesting that p53 mutation was involved in carcinogenesis. The history of high-dose radiation in early childhood and the multifocal lesions suggest the adenocarcinomas in both patients were second malignant neoplasms, with associated reactive and benign neoplastic and premalignant lesions well documented in one case. These two cases document the phenomenon of early onset of adult type tumors in survivors of childhood cancer and emphasize the need for continued clinical evaluation of patients at risk for second malignant neoplasms.

Adenocarcinoma↗

PubMed1996

Posttraumatic spinal subarachnoid cyst.

A case of posttraumatic compressive subarachnoid cyst of the thoracic spine studied by MR myelography, and myelo-CT is reported. This cyst was surgically confirmed and treated by shunting.

Adolescent↗

PubMed1996

What is a juvenile polyp? An analysis based on 21 patients with solitary and multiple polyps.

BACKGROUND: Juvenile polyps, the most common pediatric gastrointestinal polyp, have been typically characterized as either hamartomatous overgrowths or reactive inflammatory proliferations. Recent observations of excessive colonic and gastric carcinoma and dysplasia in juvenile polyposis have prompted reclassification of this entity as a premalignant condition. The relationship between solitary or multiple juvenile polyps and malignancy is less clear. PATIENTS AND METHODS: To further investigate the frequency and significance of dysplasia in juvenile polyps, we analyzed 28 polyps from 21 patients histologically and immunohistochemically for substances previously associated with neoplastic transformation in the colorectal adenomacarcinoma sequence. RESULTS: Fifteen patients had a solitary polyp, two had 2 to 9 polyps, and four had polyposis with 10 or more polyps. Most polyps exhibited inflammatory or regenerative atypia. Foci of dysplasia were noted in polyps from 11 patients, and immunoreactivity for p53 and human chorionic gonadotropin was present in 12 of the 28 polyps each. These findings were all more frequent in the polyposis specimens than in solitary polyps. CONCLUSIONS: These observations, in combination with reports of an increased risk of carcinoma in juvenile polyposis, suggest that juvenile polyps are lesions with a potential for neoplastic and malignant transformation, although they share features of an inflammatory reactive process. The implications for clinical management of patients and pathologic evaluation of juvenile polyps warrant further investigation.

Child↗

PubMed1995

False-positive interpretations of carcinoma in exfoliative respiratory cytology. Report of two cases and a review of underlying disorders.

The false-positive interpretation of malignancy is a potential pitfall of exfoliative respiratory tract cytopathology. However, the underlying causes of this problem are still relatively under-recognized. The authors herein present two additional examples in which bronchial brushing and washing specimens were misinterpreted as showing carcinoma of the lung. The first case concerned a patient with a granulomatous mass that simulated a malignancy on chest radiographs and was the apparent cause of atypical bronchial squamous metaplasia (ABSM). Exfoliated cells from the latter process were thought to explain the false-positive cytologic result in that instance. In the second case, a large-cell angiocentric T-cell lymphoma replaced the lower lobe of the left lung. It was likewise associated with ABSM as the cause of a mistaken diagnosis of carcinoma in exfoliative respiratory cytology specimens, representing the first instance of such an association of which the authors are aware. Repeated evaluation of all bronchial cytology samples by several experienced pathologists yielded no reliable observations that might have been used to avoid an erroneous interpretation in either case. A review is provided of the spectrum of underlying conditions that may be associated with false-positive respiratory cytology results.

Adult↗

PubMed1995

Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor). A clinicopathologic and immunohistochemical study of 84 cases.

Inflammatory myofibroblastic tumor (IMT) or inflammatory pseudotumor is a spindle cell proliferation of disputed nosology, with a distinctive fibroinflammatory and even pseudosarcomatous appearance. Although the lung is the best known and most common site, inflammatory myofibroblastic tumor occurs in diverse extrapulmonary locations. We report our experience with 84 cases occurring in the soft tissues and viscera of 48 female patients and 36 male patients between the ages of 3 months and 46 years (mean, 9.7 years; median, 9 years). A mass, fever, weight loss, pain, and site-specific symptoms were the presenting complaints. Laboratory abnormalities included anemia, thrombocytosis, polyclonal hypergammaglobulinemia, and elevated erythrocyte sedimentation rate. Sites of involvement included abdomen, retroperitoneum, or pelvis (61 cases); head and neck, including upper respiratory tract (12 cases); trunk (8 cases); and extremities (3 cases). The lesions ranged in size from 1 to 17 cm (mean, 6.4; median, 6.0). Excision was performed in 69 cases. Eight had biopsy only. Five patients received chemotherapy or radiation in addition to undergoing biopsy or resection as initial treatment. Sixteen patients had multinodular masses involving one region. Clinical follow-up in 53 cases revealed that 44 patients were alive with no evidence of disease, four were alive with IMT, and five were dead. Thirteen patients had one or more recurrences at intervals of 1-24 months (mean, 6 months; median, 10 months). No distant metastases were documented. The five patients who died had complications either due to the location of the lesion (heart, peritoneum, retroperitoneum, or mesentery) or related to treatment (lymphoproliferative disorder following hepatic transplantation; sepsis following wound infection). The abdominal masses were the largest. All tumors were firm and white with infiltrative borders and focal myxoid change. Three basic histologic patterns were recognized: (a) myxoid, vascular, and inflammatory areas resembling nodular fasciitis; (b) compact spindle cells with intermingled inflammatory cells (lymphocytes, plasma cells, and eosinophils) resembling fibrous histiocytoma; and (c) dense plate-like collagen resembling a desmoid or scar. Immunohistochemistry demonstrated positivity for vimentin, muscle-specific actin, smooth muscle actin, and cytokeratin consistent with myofibroblasts. Based on this series, inflammatory myofibroblastic tumor is a benign, nonmetastasizing proliferation of myofibroblasts with a potential for recurrence and persistent local growth, similar in some respects to the fibromatoses.

Adolescent↗

PubMed1994

Disseminated measles infection after vaccination in a child with a congenital immunodeficiency.

An infant boy with a congenital immunodeficiency had fatal disseminated measles after administration of a live attenuated measles vaccine. This rare complication was confirmed with molecular virologic techniques. Although efforts to expand availability of vaccinations are critically important, caution is warranted in children with potentially severe immunologic dysfunction.

Failure to Thrive↗

PubMed1994

Predictive DNA testing and prophylactic thyroidectomy in patients at risk for multiple endocrine neoplasia type 2A.

BACKGROUND: Missense germ-line mutations in the RET protooncogene are associated with multiple endocrine neoplasia type 2A (MEN 2A). Detection of these mutant alleles in kindred members predicts disease inheritance and provides the basis for preventative thyroidectomy. METHODS: A polymerase chain reaction (PCR)-based genetic test for the 19 known RET mutations was designed to study 132 members of 7 kindreds with MEN 2A. Haplotypes also were constructed using genetic markers flanking the MEN 2A locus. Plasma calcitonin (CT) concentrations were determined before and after provocative testing. RESULTS: Direct DNA testing and haplotype analysis showed that 21 of 58 kindred members at risk for disease had inherited a mutation in the RET protooncogene associated with MEN 2A. Plasma CT concentrations were elevated in 9 of the 21 family members, but were normal in 12. After genetic counseling, 13 of the 21 kindred members (6 with normal and seven with elevated plasma CT levels), consented to immediate thyroidectomy. In each patient, the resected thyroid gland showed C-cell hyperplasia with or without medullary thyroid carcinoma. There were no metastases to regional lymph nodes, and postoperative stimulated plasma CT levels were normal. CONCLUSION: The PCR-based direct DNA test for RET mutations is accurate, rapid, and reproducible. For all 132 individuals evaluated, the results of direct DNA analysis were consistent with haplotype studies. The direct test for mutations in the RET protooncogene is the preferred method for screening MEN 2A kindreds. In family members who have inherited a RET mutation, total thyroidectomy is indicated, regardless of the plasma CT values.

Adolescent↗

PubMed1994

Lipoblastoma: an embryonal tumor of soft tissue related to organogenesis.

The concept of embryomas or blastomas of connective tissues is difficult to define because of the usual association with a complex organ and typically malignant behavior. In the soft tissues, lipoblastoma is an example of a lesion which has a well-defined relationship to embryonic white fat and a capacity for differentiation. Its clinical behavior, however, is benign. This review discusses lipoblastoma in detail as an example of mesenchymal blastoma. Other potential mesenchymal blastomas and other primitive tumors of soft tissue with a capacity for differentiation are also mentioned.

Child, Preschool↗

PubMed1994

Mesenteric cysts in children.

BACKGROUND: Mesenteric cysts are uncommon benign abdominal masses. Approximately one third of patients with these lesions are children. METHODS: We reviewed our clinical records for the past 14 years (corresponding to the period of time in which ultrasonography and computed tomography became reliable methods for imaging pediatric patients) and found 10 patients with mesenteric cysts. RESULTS: We were surprised to discover that abdominal pain was a presenting complaint in all but one patient. Five of the patients had the findings of an acute surgical abdomen and were thought to have appendicitis. Two patients operated on for appendicitis were transferred to our hospital with the diagnosis of an abdominal mass. In each case the mass was a mesenteric cyst. Cyst distribution included the small-bowel mesentery in seven patients, the transverse mesocolon in two patients, and the right mesocolon in one patient. Six cases required concomitant bowel resection for the cyst removal, and all were cystic lymphangiomas. The resected specimens were described as cystic lymphangiomas in eight of the 10 cases. CONCLUSIONS: Mesenteric cysts should be considered as an origin for abdominal pain in children, particularly after exclusion of more common diagnoses. We have found ultrasonographic imaging to be a reliable method for the diagnosis of appendicitis in children and advocate its use as an initial imaging study in patients with an acute surgical abdomen and presumed appendicitis. If appendicitis is indicated unlikely by ultrasonogram, the examination can be extended to the remainder of the abdomen, which can reveal mesenteric cysts or other pathologic conditions.

Adolescent↗

PubMed1993

Laparoscopic gonadectomy in a case of testicular feminization.

Laparoscopy provides a minimally invasive technique for the accurate diagnosis of intersex problems and may also provide the opportunity for therapeutic management of these patients. Herein, we report our management of a patient with complete testicular feminization, by laparoscopic bilateral gonadectomy of fully developed intra-abdominal testes.

Adult↗

PubMed1993

An immunohistochemical comparison of chordoma with renal cell carcinoma, colorectal adenocarcinoma, and myxopapillary ependymoma: a potential diagnostic dilemma in the diminutive biopsy.

Chordoma is one of several similar appearing neoplasms in the retroperitoneum, pelvis, and abdomen with a combination of features including clear cells, with or without cytoplasmic vacuoles, papillary profiles, and a myxoid or myxohyaline stroma. The differential diagnosis of a cellular myxoid or mucinous tumor in a small biopsy, when the entire tumor is not available for pathologic examination, includes metastatic mucinous adenocarcinoma of colorectal and other similar-appearing neoplasms, renal cell carcinoma, and myxopapillary ependymoma. We compared immunohistochemical reactivity of 18 chordomas with 20 colonic adenocarcinomas, 20 renal cell carcinomas, and six myxopapillary ependymomas using antibodies to vimentin, cytokeratin, epithelial membrane antigen, S100 protein, Leu 7, glial fibrillary acidic protein, and carcinoembryonic antigen. All chordomas were immunoreactive for vimentin and cytokeratin, 83% for epithelial membrane antigen, and 83% for S100 protein. Myxopapillary ependymomas were distinguished by immunoreactivity for vimentin and glial fibrillary acidic protein in all cases and S100 protein in 50%. All colonic adenocarcinomas were positive for cytokeratin, epithelial membrane antigen, and carcinoembryonic antigen. Renal cell carcinomas were uniformly reactive for epithelial membrane antigen and cytokeratin, nonreactive for carcinoembryonic antigen, and variably reactive for S100 protein (5%) and vimentin (25%). These data indicate that a panel of immunohistochemical markers can be useful in distinguishing chordoma from potential histologic mimics.

Adenocarcinoma↗

PubMed1993

Chordoma in childhood and adolescence. A clinicopathologic analysis of 12 cases.

Chordoma is a distinctly uncommon neoplasm in the first two decades of life. To characterize further its clinicopathologic features in this age group, we studied 12 chordomas from six males and six females (age range, 1 month to 20 years at diagnosis), with a mean age of 6 years. Six tumors arose in the clivus, four in the cervical or thoracic vertebrae, and two in the lumbar and sacrococcygeal areas. The clinical presentations reflected the location. Histologically, six cases were classic chordomas; the remaining six had atypical or nonclassic features of a round cell or spindle cell tumor. Immunohistochemical stains for vimentin and cytokeratin were positive in all cases tested, whereas epithelial membrane antigen was detected in 11 examples, and S100 protein reactivity was noted in nine lesions. The tumors were uniformly nonreactive for glial fibrillary acidic protein and carcinoembryonic antigen. Electron microscopy in six cases demonstrated large primitive cells with attenuated cell junctions, whorls of cytoplasmic filaments, vacuoles, and glycogen aggregates. Ten children had died of tumor at intervals of 3 weeks to 4.5 years after diagnosis and treatment. Lung, lymph nodes, and other organs were the distant metastatic sites in seven cases. These findings imply that chordomas in children are more variable histologically and may pursue a more aggressive clinical course than their adult counterpart. Immunohistochemical studies are particularly helpful in the differentiation of atypical chordomas from other round and spindle cell neoplasms.

Adolescent↗

PubMed1993

Vascular tumors in children and adolescents: a clinicopathologic study of 228 tumors in 222 patients.

Vascular tumors in 222 children and adolescents accounted for 25 percent of all soft tissue tumors in our series of over 900 pediatric cases. Based upon standard histopathologic criteria, 203 (89 percent) were benign, 21 (9 percent) were borderline or indeterminant, and 4 (2 percent) were malignant. The mean age at diagnosis was 12 years; 26 percent (58) of cases were diagnosed in the first year of life and 57 percent (127) in the first decade. The male:female ratio was 1:2. The head and neck (80 cases, 35 percent), extremities (79 cases, 35 percent), and trunk (65 cases, 28 percent) were respectively the regional sites. Seven patients with localized angiomas had more than one lesion; 22 required re-excision for recurrent tumors. Hemangiomas of one type or another accounted for 64 percent and lymphangiomas for 29 percent of the benign group. Capillary hemangioma (73 cases, 32 percent of entire group) was the most common type, followed by lymphangioma (59 cases, 26 percent). Nine patients had diffuse angiomatosis. Borderline tumors comprised 9 percent (21 cases) of cases including ten histiocytoid hemangiomas and 7 hemangiopericytomas. Angiosarcoma (three cases) and Kaposi's sarcoma (one case) constituted the malignant tumors.

Adolescent↗

PubMed1992

Cutaneous angiosarcoma as a second malignant neoplasm after peripheral primitive neuroectodermal tumor.

Second malignant neoplasms (SMN) in late childhood or young adulthood in individuals who have been successfully treated for an initial malignancy have emerged as a late effect of therapy in survivors of childhood cancer. Although radiation therapy is frequently implicated, chemotherapy with alkylating agents and antimetabolites has also been associated with SMN. Soft tissue sarcomas are among the most frequent primary malignancies complicated by a SMN and account for a majority of nonhematolymphoid SMN. We present the clinical and pathologic findings in a patient who had a peripheral neuroepithelioma (primitive neuroectodermal tumor, PNET) of the soft tissues diagnosed at 17 years of age, was treated with high-dose irradiation and multidrug chemotherapy, and developed an angiosarcoma 14 years later. This case represents an uncommon combination of mesenchymal malignancies in a young patient with an unusually favorable clinical course following the diagnosis of PNET.

Adolescent↗

PubMed1992

Benign cutaneous histiocytic tumors in childhood and adolescence, excluding Langerhans' cell proliferations. A clinicopathologic and immunohistochemical analysis.

Clinical and light-microscopic findings were reviewed in 60 benign histiocytic tumors of the skin arising in patients who were 19 years of age or younger. These lesions were placed in five categories, based on the presence or absence of Touton giant cells, the relative content of vacuolated polygonal cells and spindle cells, and the extent of stromal collagen in the proliferations. The resulting distribution included 16 cases of classic juvenile xanthogranuloma (JXG), four examples of xanthomatous JXG, 11 "transitional" JXG, 11 histiocytomas, and 18 dermatofibromas. The histological appearances of the lesions were related to the elapsed time between their clinical presentation and biopsy sampling. Intervals of 3.5, 3.5, 3.6, 7, and 13.4 months were noted for each histologic group, respectively. Hence, "early" lesions (JXG variants) showed no differences in clinical duration, but significantly longer evolutions were observed for histiocytomas and dermatofibromas. Immunohistochemical studies were conducted utilizing antibodies to several "histiocytic" markers (CD68, cathepsin B, MAC387), CD45 antigen, and S-100 protein. Cathepsin B was universally expressed by all tumors, but its intensity and scope were variable. In addition, only dermatofibromas failed to show CD68 positivity. Scattered mononuclear inflammatory cells in the lesions were CD45 reactive, whereas other cell types were not so labeled. MAC387 was absent in all cases. These findings suggest that these lesions do indeed show histiocytic differentiation, and that they are probably related to peripheral blood monocytes antigenically. Differences in the histologic appearances of these cutaneous histiocytic proliferations of childhood may simply reflect dissimilar periods of clinical growth before biopsies are performed.

Adolescent↗