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Papers by Hilary Hargreaves

Pediatric Pathology Affiliated With the International Paediatric Pathology Association, Feb 1, 1986

Two cases of lipoblastomatosis were examined by electron microscopy. In each there was a spectrum... more Two cases of lipoblastomatosis were examined by electron microscopy. In each there was a spectrum of adipose cell differentiation from mature adipocytes to undifferentiated mesenchymal cells. The cells had various shapes and were loosely related to one another and to small blood vessels in a stroma containing sparse collagen and proteoglycan granules. Adipocytes and lipoblasts had a discrete basal lamina but this was absent in immature mesenchymal cells, which had prominent intermediate (10-nm) microfilaments and few or no lipid droplets. Neither case had foci resembling brown adipose tissue or hibernoma (large polygonal cells closely apposed to one another and to capillaries with densely packed pleomorphic mitochondria and focal undulating plasmalemmal invaginations). Both the ultrastructure of lipoblastomatosis and its characteristic loose lobular arrangement by light microscopy closely resemble human fetal "white" adipose tissue.

American journal of clinical pathology, 1979

American journal of clinical pathology, 1981

A patient who was evaluated for a voice change was found to have a large posterior mediastinal ma... more A patient who was evaluated for a voice change was found to have a large posterior mediastinal mass on chest roentgenogram. Laboratory parameters suggested hyperparathyroidism. The 190-g resected tumor had the histologic features of a parathyroid lipoadenoma, that is, a diffuse mixture of parathyroid glandular elements and fat or myxoid stroma throughout. This case report emphasizes that the large size of these rare tumors may result in herniation into unusual sites, and this gives rise to a confusing clinical presentation. Ultrastructural analysis showed a uniform population of chief cells with a distribution of cellular organelles consistent with slow hormone production and release. Similarities to normal and adenomatous chief cells are discussed. The myxoid stroma surrounding the glandular elements had the ultrastructural features of loose connective tissue.

Human Pathology, 1983

Four hibernomas and samples of developing human brown and white adipose tissue were observed. Dis... more Four hibernomas and samples of developing human brown and white adipose tissue were observed. Distinctive features of hibernomas were 1) lobules of closely apposed large polygonal cells and capillaries; 2) three principal cell types (granular eosinophilic, multivacuolated, and univacuolated) varying in prominence from case to case; 3) investment of each tumor cell by basal lamina; 4) an inverse relationship between lipid droplet size and the number of mitochondria per unit of cytoplasm; 5) pleomorphic mitochondria with dense matrixes or large, round mitochondria with transverse lamellar cristae; 6) undulating plasmalemmal invaginations; 7) micropinocytotic vesicles; 8) periodic short plasmalemmal densities; and 9) a conspicuous lack of cytoplasmic membrane systems. The frequent association of micropinocytotic vesicles and undulating plasmalemmal invaginations in proximity to capillaries strongly suggests that the invaginations represent a localized cell membrane adaptation for efficient endocytosis. In human fetal brown adipose tissue, which is first recognizable in fetuses of 21 weeks' gestational age, the most characteristic cell was the polygonal multivacuolated cell. Univacuolated cells were present in brown adipose tissue of older fetuses, and in infants and adults entire lobules containing univacuolated cells coexisted with lobules of multivacuolated cells and granular eosinophilic cells. The ultrastructure of human brown adipose tissue resembled that of hibernomas and was similar to previously described features of this tissue in animals. Developing white adipose tissue differed from brown adipose tissue by its loose plexiform arrangement of capillaries and spindle-shaped cells in less circumscribed lobules and by the absence of polygonal multivacuolated cells. The authors did not identify centripetal lobular maturation in white adipose tissue, but peripheral growth "caps" were a common finding in maturing brown adipose tissue. They consider brown adipose tissue to be a special form of adipose tissue, the variable cytologic composition of which is reflected in the histologic spectrum of hibernomas.

Medicine, 1979

Advertisement. Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for Me... more Advertisement. Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for Medicine. Enter your Email address: Wolters Kluwer Health may email you for journal alerts and information, but is committed ...

Fetal & Pediatric Pathology, 1986

Two cases of lipoblastomatosis were examined by electron microscopy. In each there was a spectrum... more Two cases of lipoblastomatosis were examined by electron microscopy. In each there was a spectrum of adipose cell differentiation from mature adipocytes to undifferentiated mesenchymal cells. The cells had various shapes and were loosely related to one another and to small blood vessels in a stroma containing sparse collagen and proteoglycan granules. Adipocytes and lipoblasts had a discrete basal lamina but this was absent in immature mesenchymal cells, which had prominent intermediate (10-nm) microfilaments and few or no lipid droplets. Neither case had foci resembling brown adipose tissue or hibernoma (large polygonal cells closely apposed to one another and to capillaries with densely packed pleomorphic mitochondria and focal undulating plasmalemmal invaginations). Both the ultrastructure of lipoblastomatosis and its characteristic loose lobular arrangement by light microscopy closely resemble human fetal "white" adipose tissue.

Cancer, 1984

This report describes two cases of giant lymph node hyperplasia (GLNH) with unusual clinicopathol... more This report describes two cases of giant lymph node hyperplasia (GLNH) with unusual clinicopathologic features, both studied with immunohistochemical techniques. In the first case, mesenteric GLNH was associated with amyloidosis and the nephrotic syndrome. In the second, GLNH developed in a patient with previously treated Hodgkin's disease. In both cases, the GLNH was of the plasma cell variant. The plasma cells of the first case contained both kappa and lambda light chains, while those in the second case contained only the lambda light chain. The presence or absence of monoclonality was not predictable from the morphology alone. Cases of GLNH with unusual clinicopathologic features are reviewed and the significance of immunohistochemical studies discussed.

Cancer, 1979

Ultrastructural studies were performed on 40 B-cell and 14 T-cell lymphomas of non-Hodgkin's type... more Ultrastructural studies were performed on 40 B-cell and 14 T-cell lymphomas of non-Hodgkin's type (NHL). Most B-cell lymphomas were comprised of neoplastic cells with morphologic features compatible with a follicular center cell origin. Dendritic reticulum cells and their desmosome-associated processes, characteristic of germinal centers, were observed in all 11 cases of nodular poorly differentiated lymphocytic lymphoma and in one of two cases of nodular "histiocytic" lymphoma, but were not identified in the lymphomas with a diffuse growth pattern. Desmosomes were observed between dendritic reticulum cells and were not found between lymphoid cells. Large neoplastic cells comprising lymphomas of "histiocytic," mixed lymphocytic "histiocytic," and "undifferentiated" types were characterized ultrastructurally and immunologically as lymphoid cells. Malignant lymphomas of well and moderately well differentiated lymphocytic types (7 cases) revealed B-cell markers, and represented a distinct homogenous group of neoplasms, with electron microscopic features most closely resembling follicular cuff lymphocytes. T-cell malignancies included lymphoblastic lymphomas (3 cases), large cell ("histiocytic") lymphomas (4 cases), lymphoepithelioid cell ("Lennert's") lymphomas (2 cases), mycosis fungoides (3 cases) and diffuse poorly differentiated lymphocytic lymphomas (2 cases). A consistent finding in the T-cell proliferations was the presence of small and/or large lymphoid cells with extremely irregular and/or convoluted nuclei, which occurred in varying proportions and with variable degrees of nuclear complexity. The nuclear irregularity evident in the neoplastic T cells was distinguishable from that observed for lymphoid cells of B-cell lymphomas. In comparing the cytoplasmic features of the Tand B-cell neoplasms ultrastructurally, the only distinguishing feature was the presence of well developed granular endoplasmic reticulum with dilated cisternae, i.s., plasmacytoid features, predictive of a B cell origin.

American journal of clinical pathology, 1999

Extramedullary plasmacytoma (EMP), solitary plasmacytoma of bone, and multiple myeloma are relate... more Extramedullary plasmacytoma (EMP), solitary plasmacytoma of bone, and multiple myeloma are related neoplasms, but EMP is clearly a distinct entity. Moreover, there are histologic and clinical similarities between EMP and marginal zone B-cell lymphomas (MZLs) displaying extensive plasma cell differentiation, suggesting a possible histogenetic relationship. The histologic and clinical features of 5 EMPs with extensive plasma cell differentiation were histologically reviewed for features of MZL. The previously diagnosed MZLs, mucosa-associated lymphoid tissue (MALT) type, of 2 patients also were reviewed. All patients were women aged 48 to 79 years. The EMPs originated in the parotid gland, lymph nodes, dura, or small bowel. The initial tumors diagnosed as MALT-type MZL were located in the lung and small bowel. All patients were treated with resection, with or without irradiation therapy. One patient also received systemic chemotherapy. All patients are alive with no evidence of diseas...

American journal of clinical pathology, 1982

Giant lymph node hyperplasia (GLNH) is generally thought to represent a benign process. A patient... more Giant lymph node hyperplasia (GLNH) is generally thought to represent a benign process. A patient with GLNH of the chest wall had part of the lymph node replaced by large nodules of infiltrating plasma cells, and a serum paraprotein of the IgG lambda type. A peroxidase-antiperoxidase immunocytochemical technic showed that the plasma cells within areas of typical appearing GLNH were polyclonal, whereas those making up the nodular infiltrates were monoclonal. The observation of a plasmacytoma arising in this lesion demonstrates the neoplastic potential of GLNH.

American journal of clinical pathology, 1982

Tumors of non-specialized gonadal mesenchyme have been reported only rarely. An intratesticular b... more Tumors of non-specialized gonadal mesenchyme have been reported only rarely. An intratesticular benign hemangioendothelioma from a 26-year-old man presented a diagnostic challenge due to the infrequency of well-defined vascular lumens. Electron microscopy was helpful in defining the vascular nature of the tumor. In spite of the cellularity of the neoplasm, there has been no recurrence or metastasis over a two and one-half year follow-up period. The histological features are compared with those of previously reported cases.

The Journal of Pediatrics, 1982

Pediatric Pathology Affiliated With the International Paediatric Pathology Association, Feb 1, 1986

Two cases of lipoblastomatosis were examined by electron microscopy. In each there was a spectrum... more Two cases of lipoblastomatosis were examined by electron microscopy. In each there was a spectrum of adipose cell differentiation from mature adipocytes to undifferentiated mesenchymal cells. The cells had various shapes and were loosely related to one another and to small blood vessels in a stroma containing sparse collagen and proteoglycan granules. Adipocytes and lipoblasts had a discrete basal lamina but this was absent in immature mesenchymal cells, which had prominent intermediate (10-nm) microfilaments and few or no lipid droplets. Neither case had foci resembling brown adipose tissue or hibernoma (large polygonal cells closely apposed to one another and to capillaries with densely packed pleomorphic mitochondria and focal undulating plasmalemmal invaginations). Both the ultrastructure of lipoblastomatosis and its characteristic loose lobular arrangement by light microscopy closely resemble human fetal "white" adipose tissue.

American journal of clinical pathology, 1979

American journal of clinical pathology, 1981

A patient who was evaluated for a voice change was found to have a large posterior mediastinal ma... more A patient who was evaluated for a voice change was found to have a large posterior mediastinal mass on chest roentgenogram. Laboratory parameters suggested hyperparathyroidism. The 190-g resected tumor had the histologic features of a parathyroid lipoadenoma, that is, a diffuse mixture of parathyroid glandular elements and fat or myxoid stroma throughout. This case report emphasizes that the large size of these rare tumors may result in herniation into unusual sites, and this gives rise to a confusing clinical presentation. Ultrastructural analysis showed a uniform population of chief cells with a distribution of cellular organelles consistent with slow hormone production and release. Similarities to normal and adenomatous chief cells are discussed. The myxoid stroma surrounding the glandular elements had the ultrastructural features of loose connective tissue.

Human Pathology, 1983

Four hibernomas and samples of developing human brown and white adipose tissue were observed. Dis... more Four hibernomas and samples of developing human brown and white adipose tissue were observed. Distinctive features of hibernomas were 1) lobules of closely apposed large polygonal cells and capillaries; 2) three principal cell types (granular eosinophilic, multivacuolated, and univacuolated) varying in prominence from case to case; 3) investment of each tumor cell by basal lamina; 4) an inverse relationship between lipid droplet size and the number of mitochondria per unit of cytoplasm; 5) pleomorphic mitochondria with dense matrixes or large, round mitochondria with transverse lamellar cristae; 6) undulating plasmalemmal invaginations; 7) micropinocytotic vesicles; 8) periodic short plasmalemmal densities; and 9) a conspicuous lack of cytoplasmic membrane systems. The frequent association of micropinocytotic vesicles and undulating plasmalemmal invaginations in proximity to capillaries strongly suggests that the invaginations represent a localized cell membrane adaptation for efficient endocytosis. In human fetal brown adipose tissue, which is first recognizable in fetuses of 21 weeks' gestational age, the most characteristic cell was the polygonal multivacuolated cell. Univacuolated cells were present in brown adipose tissue of older fetuses, and in infants and adults entire lobules containing univacuolated cells coexisted with lobules of multivacuolated cells and granular eosinophilic cells. The ultrastructure of human brown adipose tissue resembled that of hibernomas and was similar to previously described features of this tissue in animals. Developing white adipose tissue differed from brown adipose tissue by its loose plexiform arrangement of capillaries and spindle-shaped cells in less circumscribed lobules and by the absence of polygonal multivacuolated cells. The authors did not identify centripetal lobular maturation in white adipose tissue, but peripheral growth "caps" were a common finding in maturing brown adipose tissue. They consider brown adipose tissue to be a special form of adipose tissue, the variable cytologic composition of which is reflected in the histologic spectrum of hibernomas.

Medicine, 1979

Advertisement. Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for Me... more Advertisement. Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for Medicine. Enter your Email address: Wolters Kluwer Health may email you for journal alerts and information, but is committed ...

Fetal & Pediatric Pathology, 1986

Two cases of lipoblastomatosis were examined by electron microscopy. In each there was a spectrum... more Two cases of lipoblastomatosis were examined by electron microscopy. In each there was a spectrum of adipose cell differentiation from mature adipocytes to undifferentiated mesenchymal cells. The cells had various shapes and were loosely related to one another and to small blood vessels in a stroma containing sparse collagen and proteoglycan granules. Adipocytes and lipoblasts had a discrete basal lamina but this was absent in immature mesenchymal cells, which had prominent intermediate (10-nm) microfilaments and few or no lipid droplets. Neither case had foci resembling brown adipose tissue or hibernoma (large polygonal cells closely apposed to one another and to capillaries with densely packed pleomorphic mitochondria and focal undulating plasmalemmal invaginations). Both the ultrastructure of lipoblastomatosis and its characteristic loose lobular arrangement by light microscopy closely resemble human fetal "white" adipose tissue.

Cancer, 1984

This report describes two cases of giant lymph node hyperplasia (GLNH) with unusual clinicopathol... more This report describes two cases of giant lymph node hyperplasia (GLNH) with unusual clinicopathologic features, both studied with immunohistochemical techniques. In the first case, mesenteric GLNH was associated with amyloidosis and the nephrotic syndrome. In the second, GLNH developed in a patient with previously treated Hodgkin's disease. In both cases, the GLNH was of the plasma cell variant. The plasma cells of the first case contained both kappa and lambda light chains, while those in the second case contained only the lambda light chain. The presence or absence of monoclonality was not predictable from the morphology alone. Cases of GLNH with unusual clinicopathologic features are reviewed and the significance of immunohistochemical studies discussed.

Cancer, 1979

Ultrastructural studies were performed on 40 B-cell and 14 T-cell lymphomas of non-Hodgkin's type... more Ultrastructural studies were performed on 40 B-cell and 14 T-cell lymphomas of non-Hodgkin's type (NHL). Most B-cell lymphomas were comprised of neoplastic cells with morphologic features compatible with a follicular center cell origin. Dendritic reticulum cells and their desmosome-associated processes, characteristic of germinal centers, were observed in all 11 cases of nodular poorly differentiated lymphocytic lymphoma and in one of two cases of nodular "histiocytic" lymphoma, but were not identified in the lymphomas with a diffuse growth pattern. Desmosomes were observed between dendritic reticulum cells and were not found between lymphoid cells. Large neoplastic cells comprising lymphomas of "histiocytic," mixed lymphocytic "histiocytic," and "undifferentiated" types were characterized ultrastructurally and immunologically as lymphoid cells. Malignant lymphomas of well and moderately well differentiated lymphocytic types (7 cases) revealed B-cell markers, and represented a distinct homogenous group of neoplasms, with electron microscopic features most closely resembling follicular cuff lymphocytes. T-cell malignancies included lymphoblastic lymphomas (3 cases), large cell ("histiocytic") lymphomas (4 cases), lymphoepithelioid cell ("Lennert's") lymphomas (2 cases), mycosis fungoides (3 cases) and diffuse poorly differentiated lymphocytic lymphomas (2 cases). A consistent finding in the T-cell proliferations was the presence of small and/or large lymphoid cells with extremely irregular and/or convoluted nuclei, which occurred in varying proportions and with variable degrees of nuclear complexity. The nuclear irregularity evident in the neoplastic T cells was distinguishable from that observed for lymphoid cells of B-cell lymphomas. In comparing the cytoplasmic features of the Tand B-cell neoplasms ultrastructurally, the only distinguishing feature was the presence of well developed granular endoplasmic reticulum with dilated cisternae, i.s., plasmacytoid features, predictive of a B cell origin.

American journal of clinical pathology, 1999

Extramedullary plasmacytoma (EMP), solitary plasmacytoma of bone, and multiple myeloma are relate... more Extramedullary plasmacytoma (EMP), solitary plasmacytoma of bone, and multiple myeloma are related neoplasms, but EMP is clearly a distinct entity. Moreover, there are histologic and clinical similarities between EMP and marginal zone B-cell lymphomas (MZLs) displaying extensive plasma cell differentiation, suggesting a possible histogenetic relationship. The histologic and clinical features of 5 EMPs with extensive plasma cell differentiation were histologically reviewed for features of MZL. The previously diagnosed MZLs, mucosa-associated lymphoid tissue (MALT) type, of 2 patients also were reviewed. All patients were women aged 48 to 79 years. The EMPs originated in the parotid gland, lymph nodes, dura, or small bowel. The initial tumors diagnosed as MALT-type MZL were located in the lung and small bowel. All patients were treated with resection, with or without irradiation therapy. One patient also received systemic chemotherapy. All patients are alive with no evidence of diseas...

American journal of clinical pathology, 1982

Giant lymph node hyperplasia (GLNH) is generally thought to represent a benign process. A patient... more Giant lymph node hyperplasia (GLNH) is generally thought to represent a benign process. A patient with GLNH of the chest wall had part of the lymph node replaced by large nodules of infiltrating plasma cells, and a serum paraprotein of the IgG lambda type. A peroxidase-antiperoxidase immunocytochemical technic showed that the plasma cells within areas of typical appearing GLNH were polyclonal, whereas those making up the nodular infiltrates were monoclonal. The observation of a plasmacytoma arising in this lesion demonstrates the neoplastic potential of GLNH.

American journal of clinical pathology, 1982

Tumors of non-specialized gonadal mesenchyme have been reported only rarely. An intratesticular b... more Tumors of non-specialized gonadal mesenchyme have been reported only rarely. An intratesticular benign hemangioendothelioma from a 26-year-old man presented a diagnostic challenge due to the infrequency of well-defined vascular lumens. Electron microscopy was helpful in defining the vascular nature of the tumor. In spite of the cellularity of the neoplasm, there has been no recurrence or metastasis over a two and one-half year follow-up period. The histological features are compared with those of previously reported cases.

The Journal of Pediatrics, 1982