Louis P. Dehner

Malignant small cell tumor of the thoracopulmonary region in childhood. A distinctive clinicopathologic entity of uncertain histogenesis

This report describes a unique clinicopathologic entity characterized as a malignant small cell tumor of the thoracopulmonary region in 20 children and adolescents (average age 14.5 years). There was a female predilection (75%) for this tumor which appeared to originate in the soft tissues of the chest wall or the peripheral lung. The neoplasm tended to recur locally and did not seem to disseminate as widely as some of the other small cell tumors of childhood (rhabdomyosarcoma, Ewings sarcoma, neuroblastoma and malignant lymphoma). However, the median survival was only 8 months. Electron microscopy of 3 cases suggested a neuroepithelial derivation, but, at the present, the histogenesis remains a subject for further investigation.

Pleuropulmonary blastoma the so-called pulmonary blastoma of childhood

The authors studied 11 pediatric intrathoracic neoplasms that share clinicopathologic features and constitute a specific tumor in children. These neoplasms were intrapulmonary, mediastinal, or pleural‐based masses. A common histologic feature was the presence of small, primitive cells with blastematous qualities separated by an uncommitted stroma. Focal rhabdomyosarcomatous, chondrosarcomatous, and liposarcomatous differentiation was observed. Epithelial components had bland cytologic features and probably represented entrapped benign epithelium and/or mesothelium. The prognosis for these patients was grave; seven patients died of their disease 5 months to 2 years after diagnosis. Two patients have survived diseasefree for 10 and 12 years after diagnosis. Two recent cases are alive 14 and 32 months after diagnosis. This neoplasm constitutes a distinct entity which has been reported in the literature as pulmonary blastoma in children. It differs from pulmonary blastema in adults because of its variable anatomic location, primitive embryonic‐like blastema and stroma, absence of a carcinomatous component, and potential for sarcomatous differentiation. The designation of pleuropulmonary blastoma is suggested by the authors for these intrathoracic neoplasms of childhood rather than pulmonary blastoma for histogenetic and anatomic reasons. The clinicopathologic features, immunophenotypic and ultrastructural characteristics, possible histogenesis, and differential diagnosis of these neoplasms from other thoracopulmonary tumors in children serve as the basis for this report.

Lymphoreticular disorders in primary immunodeficiencies: New findings based on an up‐to‐date histologic classification of 35 cases

A histologic review was undertaken of 35 lymphoreticular disorders that developed in primary immunodeficiency patients from the Immunodeficiency Cancer Registry. Twenty‐one (60%) of the lesions were non‐Hodgkins lymphomas: these included eight B‐immunoblastic sarcomas. Eight (23%) of the lesions were Hodgkins disease, with a high frequency of lymphocytic depletion type in an unusually young age group. Three lesions (8.5%) represented abnormal proliferative processes, which could not be definitely categorized as either benign or malignant. There were only two acute lymphoblastic leukemias (6%). Differences were found between lymphomas arising in Wiskott‐Aldrich syndrome and those occurring in ataxia‐telangiectasia; this suggests that different pathogenetic mechanisms might operate in their development. The lymphomas in Wiskott‐Aldrich syndrome were all of non‐Hodgkins type, predominantly B‐immunoblastic sarcomas, and presented as localized extranodal infiltrates. The lymphomas in ataxia‐telangiectasia were either Hodgkins disease, mostly of lymphocytic depletion type, or non‐Hodgkins lymphomas of the histologic subtypes associated with 14q translocations.

Pleuropulmonary blastoma : a marker for familial disease

OBJECTIVEnTo catalog and evaluate patterns of disease in families of children with pleuropulmonary blastoma (PPB).nnnMETHODSnData have been collected since 1988 on 45 children with PPB and their families. All pathologic materials were centrally reviewed. Preliminary molecular genetic analyses were performed when possible.nnnRESULTSnIn 12 of 45 patients, an association was found between PPB and other dysplasias, neoplasias, or malignancies in the patients with or in their young relatives. The diseases found to be associated with PPB include other cases of PPB, pulmonary cysts, cystic nephromas, sarcomas, medulloblastomas, thyroid dysplasias and neoplasias, malignant germ cell tumors, Hodgkin disease, leukemia, and Langerhans cell histiocytosis. Abnormalities of the p53 tumor suppressor gene, Wilms tumor suppressor gene (WT1), and the putative second genetic locus for Wilms tumor (WT2) were not found in preliminary investigations.nnnCONCLUSIONSnThe occurrence of PPB appears to herald a constitutional and heritable predisposition to dysplastic or neoplastic disease in approximately 25% of cases. All patients with PPB and their families should be investigated carefully. Further research of this new family cancer syndrome may provide insight into the genetic basis of these diseases.

Malignant mixed müllerian tumors: An immunohistochemical study of 47 cases, with histogenetic considerations and clinical correlation☆

Forty-seven cases of malignant mixed müllerian tumors were reviewed histologically and studied immunohistochemically with three major objectives: to analyze the histogenetic relationship between the carcinomatous and sarcomatous components of these neoplasms, to ascertain the practical role of immunohistochemical studies in diagnosis and classification, and to determine the prognostic significance of immunohistochemically verified rhabdomyoblastic and neuroendocrine differentiation. Epithelial differentiation (cytokeratin and/or epithelial membrane antigen expression) was confirmed in all carcinomatous components; within the sarcomatous areas, it was identified among individual cells (60% of cases) and within poorly formed clusters of cells (57% of cases). There was a statistically significant tendency for concordant expression of alpha-1-antichymotrypsin, Leu-M1, S-100, Leu-7, and neuron-specific enolase between the carcinomatous and sarcomatous components of individual cases. These two findings provide evidence of common origin for the sarcomatous and carcinomatous components of these neoplasms. Histologic review of metastases in 21 cases revealed a biphasic composition in the majority of metastatic lesions (62%), another feature that further supports a common origin for the two components. From a practical standpoint, immunohistochemistry may be helpful in accentuating the biphasic pattern of these neoplasms and in verifying the presence of rhabdomyoblastic differentiation. In most cases, however, careful morphologic examination and thorough sampling will suffice for correct diagnosis and subclassification. The presence of heterologous, rhabdomyoblastic, or neuroendocrine differentiation did not have a statistically significant influence on survival; the last of these was associated with a tendency for a more rapidly fatal course.

Malignant melanotic neuroectodermal tumor of infancy. A clinical, pathologic, ultrastructural and tissue culture study

The melanotic neuroectodermal tumor of infancy is an uncommon neoplasm typically of early childhood which has a predilection for the head and neck region, particularly the maxilla. Except for one previous example in the literature, this tumor has consistently behaved in a benign fashion. This study documents the clinical course and pathologic findings of a tumor which began in the maxilla of a 4‐month‐old boy, followed by a local recurrence, metastasis to a cervical lymph node and finally, widespread dissemination and death at 18 months, 24 months and 38 months, respectively. The tumor was initially composed of nests consisting of melanin‐containing cells and small dark cells. An elevated vanillylmandelic acid level was recorded during the course of the disease. At autopsy, the tumor in lymph nodes, liver, bone and soft tissues had a monotonous pattern of small dark cells similar to a conventional neuroblastoma. Previous ultrastructural studies indicate that the melanotic neuroectodermal tumor of infancy is composed of melanocytes and neuroblast‐like cells. Our case provided the unique opportunity to examine in sequence the ultrastructural and in vitro characteristics of a recurring and eventually metastasizing melanotic neuroectodermal tumor. Although the neuroblast‐like cells were initially difficult to identify by electron microscopy, a melanin‐producing cell line and a separate nonpigmented cell line were successfully isolated from various tumor explants. Various stages of melanosome development were identified in the pigmented cells from the local recurrences and in vitro. Dibutyryl cAMP accentuated the formation of pigment and dendritic development in the melanocytes and dendrites only in the small nonpigmented cells. Electron dense granules were observed in the cultured smaller cells and also in the lymph node and soft tissue metastases. Tyrosine hydroxylase activity was demonstrated in the neuroblast‐like cells. In the final biopsy and autopsy material, only the neuroblast‐like cells remained and the tumor resembled a conventional neuroblastoma.

Placental alkaline phosphatase immunoreactivity in testicular germ-cell neoplasms.

We analyzed the sensitivity of a polyclonal antibody to placental alkaline phosphatase (PLAP) in labelling testicular germ-cell neoplasms, by utilizing the peroxidase-antiperoxidase technique. The immunoreactivity of 89 germ-cell tumors for PLAP was as follows: 98% of cases with seminomatous elements were PLAP-positive; 97% of embryonal carcinomas and 85% of endodermal sinus tumors also showed reactivity. Cytotrophoblastic cells were focally immunoreactive in one of two cases with choriocarcinomatous elements. Staining for PLAP was strongest and most diffuse in seminomas. Intratubular germ-cell neoplasia (ITGCN) or carcinoma in situ was present in 53 (84%) of 63 specimens that had adjacent seminiferous tubules available for evaluation; PLAP was demonstrated in 98% of these. In addition, the germ-cell elements in 11 gonadoblastomas were immunoreactive for PLAP. One of 17 cases of undescended testes had ITGCN that was also strongly immunoreactive, but the remaining 16 cases were negative. Five dysgenetic gonads without ITGCN were studied, and one was immunoreactive for PLAP. Three testicular biopsy specimens from infertile men without ITGCN were PLAP-negative. Our findings indicate that PLAP is a highly sensitive marker for seminomas, for the majority of embryonal carcinomas and endodermal sinus tumors of the testis, and for ITGCN.

Soft Tissue Tumors in First Year of Life: A Report of 190 Cases

A comprehensive review of soft tissue tumors in children and adolescents disclosed the presence of 190 neoplasms in 183 patients, which were diagnosed in infants between birth and 12 months of age; these infants represented approximately 20% of our entire pediatric soft tissue tumor series. In excess of 75% of cases were pathologically benign with the hemangioendothelioma, lymphangioma, and fibromatosis-myofibromatosis constituting the majority of cases in this category. Fibrous histiocytoma and lipoblastoma were the other two benign entities. Congenital-infantile fibrosarcoma was considered a borderline tumor because of its infrequently manifested potential for metastasis; none of the 13 cases in the present study behaved in a malignant fashion. Embryonal rhabdomyosarcoma and peripheral primitive neuroectodermal tumor were the two principal types (17 of 27 cases) of malignant soft tissue tumors. In contrast to soft tissue tumors in the first two decades, those in the first year of life were more often benign despite their cellularity and presence of mitotic activity. Fibroblastic-myofibroblastic tumors were more frequent in this young age group, whereas neurogenic and myogenic tumors were relatively more common in children older than 1 year of age. The trunk and head and neck region were the preferred topographic sites rather than the extremities, which was the case in children beyond the first year of life.

Malignant rhabdoid tumor of the vulva: is distinction from epithelioid sarcoma possible? A pathologic and immunohistochemical study.

Epithelioid sarcoma (ES) and malignant rhabdoid tumor (MRT) have heretofore been regarded as two separate clinicopathologic entities. However, they have some histologic similarities, and both represent histogenetic and phenotypic enigmas. This study reports the pathologic and immunohistochemical findings of four vulvar neoplasms occurring in young women that represented diagnostic dilemmas because of their similarity to both ES and MRT. Only one case had the classic histologic features of ES, whereas, in our opinion, the other three cases fulfilled the histologic criteria of MRT, despite the fact that two of the three cases were reported earlier as examples of ES. Neither electron microscopy nor immunohistochemistry has been found to be helpful in separating ES from MRT, mainly because they share several ultrastructural and immunophenotypic features. The behavior of these vulvar tumors—ours and the few published examples of ES—is generally aggressive, more in keeping with MRT than classic ES. We believe that some, if not most, putative ES of the vulva are in fact MRT, a neoplasm with an unfavorable prognosis.

Regressing atypical histiocytosis: A cutaneous proliferation of atypical neoplastic histiocytes with unexpectedly indolent biologic behavior

Regressing atypical histiocytosis (RAH) of skin is a cutaneous noduloulcerative proliferation of atypical neoplastic histiocytes with concomitant polymorphous inflammation, frequently pronounced epidermal hyperplasia, and an unexpectedly indolent biologic course. Spontaneous regression and recurrence without systemic spread were the course in follow‐up periods of over six years. Histopathologically, characteristic‐appearing atypical mononuclear and multinucleated “RAH” cells showed erythrophagocytosis as well as ultrastructural, surface marker, and enzyme cytochemical features indicating histiocytic differentiation. Cytogenetic analysis showed aneuploidy and several marker chromosomes including 14q+. Its benign biologic course clearly distinguished this entity from malignant histiocytosis, large cell lymphoma, and Hodgkins disease. The histiocytic atypical cells further distinguished it from the T‐cell lesions of the skin, such as mycosis fungoides and lymphomatoid papulosis. This entity is readily confused with malignant lymphoreticular disease, melanoma, or squamous carcinoma.