Biomedical subjects

C M Coffin

Publications and source records attributed to C M Coffin.

At least 19 recordsLinked to original sources

PubMed2000

Therapy associated changes in childhood tumors.

Contemporary treatment regimens for the common solid tumors of childhood have led to increased numbers of post-treatment pathologic specimens from survivors. Current therapeutic strategies for childhood cancers in North America require an accurate pathologic diagnosis and stratify patients based on combinations of clinical, biological, and pathologic features. In several tumor systems, the pathologic response to therapy also modifies the treatment regimen. Accurate pathologic interpretation of such specimens is critical in providing useful prognostic information for therapeutic decisions. Standardized handling of post-therapy pathologic specimens, appropriate use of molecular and genetic studies, consideration of the differential diagnoses, and assessment of the potential biologic significance of therapy-induced pathologic changes are, therefore, critical for patient management and determination of treatment protocols.

Adolescent↗

PubMed2000

Cystic testicular lesions in the pediatric population.

PURPOSE: We present the etiology, histological evaluation and management of all cystic lesions of the pediatric testis. MATERIALS AND METHODS: Illustrative cases from our experience are reported with a literature review of all possible diagnoses. RESULTS: Included in the differential diagnosis of cystic testis lesions in children are epidermoid cyst, dermoid cyst, prepubertal teratoma, juvenile granulosa cell tumor, cystic dysplasia of the rete testis, testicular cystic lymphangioma, simple cyst and cystic degeneration after torsion. Testis sparing surgery is feasible in many circumstances. CONCLUSIONS: Cystic lesions of the pediatric testis are rare but represent an interesting group of diagnoses. Patient age at presentation, examination features, tumor markers and sonographic appearance may assist in making a presumptive and occasionally definitive diagnosis preoperatively. Based on the likely diagnosis enucleation or partial orchiectomy may be considered when performed with frozen section histological assessment. A thorough understanding of potentially cystic testis lesions in children leads to the best management choices and often to preservation of a substantial portion of the affected testis.

Cysts↗

PubMed1999

Benign and malignant hepatocellular tumors: evaluation of tumoral enhancement after mangafodipir trisodium injection on MR imaging.

The aim of this work was to study the ability of mangafodipir trisodium (Mn-DPDP)-enhanced MR imaging in differentiating malignant from benign hepatocellular tumors. Eleven patients with pathologically proved hepatocellular carcinomas, six with focal nodular hyperplasias, and one with a single hepatocellular adenoma were examined by spin-echo and gradient-echo T1-weighted sequences before, 1 h after, and 24 h after intravenous injection of Mn-DPDP (5 micromol/kg). Quantitative analysis including enhancement and lesion-to-liver contrast-to-noise ratio, and qualitative analysis including the presence of a central area and a capsule were done on pre- and post-Mn-DPDP-enhanced images. Enhancement was observed in all the tumors with significant improvement (p < 0.05) in contrast-to-noise ratio 1 h after, and 24 h after intravenous injection of Mn-DPDP. There were no significant differences in the mean enhancement and the mean contrast-to-noise ratio (CNR) between benign and malignant tumors. No enhancement was seen within internal areas observed in 7 hepatocellular carcinomas, and in 5 focal nodular hyperplasias, and within capsules which were observed in 9 hepatocellular carcinomas. In our study, Mn-DPDP increased CNR of both benign and malignant tumors but did not enable differentiation between benign and malignant tumors of hepatocellular nature.

Adenoma, Liver Cell↗

PubMed1999

Comparison of DNA ploidy, histologic, and immunohistochemical findings with clinical outcome in inflammatory myofibroblastic tumors.

Inflammatory myofibroblastic tumors (IMTs) are uncommon spindle cell proliferations that occur in the viscera and soft tissue of children and young adults. Their biologic potential is indeterminate: 25% of IMTs recur, and rare examples undergo malignant transformation (MT). This study investigates histologic features, DNA ploidy, and expression of apoptotic regulatory and oncogenic proteins in IMTs in an attempt to identify those deviances that might correlate with aggressive behavior or MT. Twenty-four formalin-fixed, paraffin-embedded IMTs for which clinical outcome was known were evaluated for cellularity, cytologic atypia, mitoses, ganglion-like cells, inflammatory infiltrate, DNA ploidy by flow cytometric examination, and bax, bcl-2, p53, and c-myc expression by immunohistochemical analysis. Sixteen (67%) of the IMTs did not recur, 6 (25%) recurred, and 2 (8%) underwent MT. Cellular atypia was observed in 69% of the cases without recurrence, 100% with recurrence, and 100% with MT. Ganglion-like cells were present in 56, 100, and 100% of the IMTs without recurrence, with recurrence, and with MT, respectively. There was no difference in the degree of cellularity, mitoses, or inflammatory infiltrate among the outcome groups. All of the tumors expressed bax, and none expressed c-myc. Two (8%) were immunoreactive for p53, one of which recurred and one of which underwent MT. bcl-2 expression was observed in 9 (37%) of the IMTs, with no difference among the three groups. Two IMTs were aneuploid, one of which underwent MT. Neither morphologic evaluation for cellularity, mitosis, or inflammatory infiltrate nor expression of bax or c-myc were useful for prediction of clinical outcome. The combination of atypia, ganglion-like cells, p53 expression and DNA ploidy analysis, however, might be useful to identify IMTs that might undergo MT or pursue a more aggressive clinical course with recurrences.

Adolescent↗

PubMed1999

Lymphangioma and congenital pulmonary lymphangiectasis: a histologic, immunohistochemical, and clinicopathologic comparison.

Lymphangioma (LA) and congenital pulmonary lymphangiectasis (CPL) are part of a spectrum of lymphatic disorders less well characterized than other vascular tumors and malformations. Recent studies showed proliferative and involutional growth phases for hemangiomas that distinguish them from malformations. We investigated immunohistochemical reactivity and proliferative activity to determine whether a similar diagnostically/prognostically useful pattern exists for LA, comparing LA with CPL as a malformative lesion. Immunohistochemical tests for vimentin, Factor VIII-related protein, CD31, CD34, CD45RO, smooth muscle actin, Type IV collagen, MIB-1, bcl-2, and topoisomerase IIalpha were performed on 20 LAs and 10 cases of CPL. Giemsa staining was also performed to quantitate mast cells. Clinicopathologic correlation was performed by medical record review. LA and CPL shared a similar immunohistochemical profile for vimentin, Factor VIII-related protein, CD31, CD34, smooth muscle actin, CD34, and, to a lesser extent, CD45RO. CD31 and CD34 displayed the most uniform pattern of endothelial reactivity, although CD34 had high background staining. bcl-2 was negative. Four LAs exhibited focal low reactivity for MIB-1 and topoisomerase IIalpha; recent infection and thrombosis were associated conditions. LAs displayed seven-fold more mast cells and more reactive T lymphocytes than did cases of CPL. LA and CPL had similar immunohistochemical profiles; LA resembled vascular malformations more than hemangiomas. CD31 and CD34 were useful for detection of small lymphatics at resection margins of LA, a feature associated with recurrence. MIB-1 and topoisomerase IIalpha expression were associated with inflammatory, thrombotic, or reactive processes and were not diagnostically useful. Abundant mast cells, which also were noted in other soft tissue neoplasms, prompt speculation concerning their role in the growth of LAs.

Adolescent↗

PubMed1998

Peripheral primitive neuroectodermal tumor presenting with diffuse cutaneous involvement and 7;22 translocation.

We report an unusual case of peripheral primitive neuroectodermal tumor (pPNET) in an infant presenting with congenital cutaneous nodules and a t(7;22)(p21;q11.2). The biologic behavior of the tumor diverged over time from a slowly growing tumor with multiple cutaneous nodules to a more aggressive neoplasm characterized by pulmonary metastases and a soft tissue mass showing additional cytogenetic alterations.

Chromosomes, Human, Pair 22↗

PubMed1998

Pathologic evaluation of pediatric soft tissue tumors.

The subject of soft tissue tumors in children has some parallels with the same topic in adults, but many of the details clearly establish the existence of distinct differences. Most soft tissue tumors in adults arise in the extremities or in the superficial and deep soft tissues elsewhere in the body, and most tumors are neoplastic, whether they are benign or malignant. In children, some of the most common soft tissue tumors may not be neoplastic at all, but rather are malformations of the supporting mesenchymal tissues. There is a common classification of soft tissue tumors that is applicable to both pediatric- and adult-type neoplasms. Although some of the "adult"-type soft tissue tumors may occur in children, the reverse situation is very uncommon. Because pediatric soft tissue tumors are not seen with any regularity by many pathologists in a practice dominated by adult cases, there is less familiarity and more uncertainty about these tumors in children. The differential diagnosis of a malignant soft tissue tumor in a child encompasses the broad morphologic spectrum of spindle cells, round cells, or combined-pattern neoplasms. The diagnostic process is complex and may necessitate an array of ancillary studies, including immunohistochemistry, electron microscopy, and molecular diagnostics. After a decision is reached to excise a soft tissue sarcoma in a child, many of the steps in the examination of the specimen and the reporting of results for diagnostic and staging purposes are similar to those in the evaluation of a soft tissue sarcoma in an adult. However, it is important for the pathologist and other members of the multidisciplinary health care team to remember that a soft tissue tumor in a child may have genetic implications that directly influence the care of the patient and the family and for which the excised tissue offers a potentially invaluable resource for future studies.

Adolescent↗

PubMed1998

Extrapulmonary inflammatory myofibroblastic tumor: a clinical and pathological survey.

Inflammatory myofibroblastic tumor (IMT) or inflammatory pseudotumor was initially recognized in the lung, and somewhat later, a similar-appearing pathological process was reported in the liver. Presently, this tumor has been described in virtually all major organs and extrapulmonary sites with a few exceptions. It was thought initially that the IMT was nonneoplastic and represented an aberrant inflammatory response despite its gross and microscopic features of a spindle cell neoplasm. The inflammatory hypothesis about the pathogenesis has been more readily accommodated in the lung than in the extrapulmonary sites of involvement. Some cases, however, were accompanied by the constitutional symptoms and signs of an inflammatory process, which resolved in most cases after surgical resection. There were some pathological aspects of the IMT that seemingly contradicted its purely inflammatory nature, including its potential for local recurrence; development of multifocal, noncontiguous tumors; infiltrative local growth; vascular invasion; and malignant transformation. These pathological features seemed to support the hypothesis that the IMT is a neoplastic process, which has been augmented by reports that these tumors have clonal characteristics. Other studies have suggested that IMTs of the liver and spleen are associated with the Epstein-Barr virus. From the diagnostic perspective, there are several potential difficulties that the pathologist may encounter in the examination of one of these tumors. Just as it was true 60 years ago, the potential for a pathological diagnosis of one or another type of spindle cell sarcoma has not diminished with time. Because these tumors have a predilection for children, embryonal rhabdomyosarcoma is another diagnostic temptation when an IMT presents in the bladder or other hollow viscus. The IMT should probably be regarded as a soft tissue-mesenchymal tumor with an indeterminant or low malignant potential, which is a somewhat indefinite but realistic prognostic category.

Cytogenetics↗

PubMed1998

Inflammatory myofibroblastic tumor, inflammatory fibrosarcoma, and related lesions: an historical review with differential diagnostic considerations.

The concept of the inflammatory myofibroblastic tumor (IMT) has evolved from an already perplexing pathological process, the inflammatory pseudotumor, which was initially recognized in the lung and regarded as a pseudoneoplasm, although its histological features resembled a spindle cell sarcoma. Despite the pathological findings and their apparent prognostic implications, most affected individuals regardless of the primary site have had favorable clinical outcomes. The designation of inflammatory pseudotumor came to be widely accepted, although these lesions were clearly tumors or masses that may or may not have been pseudoneoplasms. An aberrant or exaggerated response to tissue injury without an established cause has generally been favored as the pathogenesis of the inflammatory pseudotumor or IMT. Once the myofibroblast was identified and its function in tissue repair was established, this cell type was found in a variety of soft tissue lesions from nodular fasciitis to malignant fibrous histiocytoma. The myofibroblast was eventually recognized as the principal cell type in the inflammatory pseudotumor, which provided the opportunity to redesignate this tumor as IMT. Some of the clinical and pathological aspects of the IMT began to suggest the possibility that these lesions are more similar to neoplasms than a postinflammatory process. Another step in the evolution of the inflammatory pseudotumor and IMT occurred with the report of a mesenteric or retroperitoneal tumor with similar pathological features to the latter tumors but with more aggressive behavior to warrant an interpretation of malignancy as an inflammatory fibrosarcoma. The IMT and inflammatory fibrosarcoma appear to have many overlapping clinical and pathological features. These tumors are histogenetically related, and if they are separate entities, they are differentiated more by degrees than absolutes. The therapeutic approach to these tumors should relay primarily on surgical resection. Studies in the future may possibly resolve the question whether the IMT and inflammatory fibrosarcoma are synonomous or closely related entities.

Diagnosis, Differential↗

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↗

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↗