Malignant histiocytosis: a histological and ultrastructural study of lymph nodes in six cases

A morphological, histological, and ultrastructural investigation was carried out on a series of six cases of malignant histiocytosis observed between 1973 and 1977. All lymph nodes were obtained prior to treatment. The histological findings revealed that the proliferating cell type was in all cases represented by histiocytes of varying degrees of atypia and with consistent phagocytic activity. In four cases, the histiocytic cellular proliferation also showed some degree of cohesiveness and, in two cases, there was capsular invasion. In three cases blood vessel invasion by malignant cells could be seen within the lymph node and in the surrounding tissue. On electron microscopy the tumour cells of malignant histiocytosis appeared to be pleomorphic with three types of cells: undifferentiated cells, histiocytes with variable degrees of differentiation, and cells with intermediate features. In particular, nonphagocytic and actively phagocytic histiocytes could be identified. The histological and ultrastructural data further support the idea that malignant histiocytosis is a disease that is related to the neoplastic proliferation of moderately differentiated histiocytes and their precursors. The latter may undergo various transformations with either apparently benign or definitely atypical morphological features.     

Malignant histiocytosis in childhood: Morphologic Considerations

Eight cases diagnosed over a ten-year period as malignant histiocytosis (MH; histiocytic medullary reticulosis) were reviewed to clarify diagnostic criteria for the childhood disease and to identify sources of diagnostic confusion. Five of the eight cases met the authors' criteria for diagnosis; i.e., they were characterized by loose mixed infiltrates composed of three cell types--well-differentiated histiocytes, prohistiocytes, and malignant histiocytes--and they had no leukemic phase. Three cases did not share these features and were reclassified. The liver was found to be the organ most useful in premortem diagnosis, and immunoperoxidase staining for immunoglobulins and lysozyme was also helpful. The clinical and morphologic features of the five cases confirm the authors' view that diagnoses of MH should be limited to cases in which there is a loose pleomorphic population of all three types of histiocytes and that cases with monomorphous populations of aggregated malignant cells should be classified as lymphomas.     

Malignant lymphoepithelial lesion of the salivary gland

Eight cases of malignant lymphoepithelial lesion (MLEL) of major salivary glands, seven of which occurred in Southern Chinese patients, are reported. All but two of the patients were older than 40 years of age; there were five male and three female patients. The parotid and submandibular glands were the sites of origin in equal numbers of cases. Six patients had elevated titers of serum IgA against Epstein-Barr virus capsid antigen. Seven remained well after surgery and local radiation therapy, and one died of miliary tuberculosis without evidence of residual neoplasm. Histologically, MLELs were characterized by syncytial clumps of large cells with vesicular nuclei and prominent nucleoli, admixed with abundant small lymphocytes and plasma cells. Two features not emphasized previously in the literature were the presence of reactive histiocytes in some epithelial islands, producing a starry sky pattern, and perineural invasion, which was identified in four cases. The tumor cells showed strong immunostaining for cytokeratin. The literature concerning this rare tumor is reviewed, and the differential diagnosis between MLEL and benign lymphoepithelial lesion, metastatic undifferentiated carcinoma, and malignant lymphoma is discussed.     

The application of the metalophil method for the demonstration of histiocytes

The metalophil method has been performed on 250 sections of a wide variety of inflammatory and neoplastic lesions in which different types of histiocytes might be encountered. In lymph nodes, dendritic histiocytes related to the B-lymphocyte system were consistently metalophil. They appeared as small cells with slender extensions in lymph nodes with follicular hyperplasia and/or sinus histiocytosis and in some cases of Hodgkin's lymphomas or as larger pleomorphic cells in primary or secondary malignancies of lymph nodes. Small, rounded cells were seen in some cases of marked paracortical reaction, in dermatopathic lymphadenitis and in some cases of mycosis fungoides. These cells most probably represented Langerhans cells and interdigitating reticulum cells, which are related to the T-lymphocyte system. Interdigitating cells become metalophil when they are activated or proliferating. Epithelioid cells in different benign and malignant lesions were metalophil like the sinus histiocytes of the lymph nodes, the Kupffer cells of the liver and the alveolar histiocytes in the lung. Foreign-body giant cells in lymph nodes after lymphography were also metalophil. The sinus lining cells lymph nodes were also well-delineated. Histiocytes of malignant histiocytic proliferations were sometimes metalophil as were the so-called histiocytes in malignant fibrous histiocytomas. Epithelial cells, particularly the basal cells of squamous epithelium often take up the silver. Carcinoma cells were sometimes metalophil and the method appeared not to be of value in the differentiation between metastatic carcinomas and lymphomas. The most promising application seems to be the study of the distribution of dendritic histiocytes in malignant proliferations of B-lymphocytes.     

Lymphomas of true histiocytic origin. Expression of different phenotypes in so-called true histiocytic lymphoma and malignant histiocytosis.

The authors determined the phenotypes of neoplastic cells in true histiocytic lymphoma and malignant histiocytosis by using a large panel of monoclonal antibodies and enzyme histochemistry procedures. Although the phenotypes overlapped slightly, the authors noted a distinct pattern in these tumors. The tumor cells of malignant histiocytosis generally expressed the monocyte markers CD11b, CD11c, CD14, and CD45, especially after induction with phorbol ester. In contrast, the tumor cells of true histiocytic lymphoma exhibited a marker expression very similar to that of Reed-Sternberg cells in Hodgkin's disease. These cells expressed markers CD30, 2H9, and 1A2, but rarely expressed CD11b, CD11c, CD14, or CD45. Regardless of their cytologic features, the tumor cells from both types of histiocytic lymphoma exhibited diffuse nonspecific esterase and acid phosphatase activities, and they expressed histiocyte markers CD15, CD68, LN5, 1E9, and M387 to varying degrees. The tumor cells from both lymphomas did not exhibit T- or B-cell markers, T-cell receptor or immunoglobulin gene rearrangements, or gene translation products, even when they were induced with phorbol ester. The phenotypic expression in these two histiocytic malignancies suggests that they are derived from different types of histiocytes, or from histiocytes in different stages of maturation or differentiation, or from histiocytes that have distinct mechanisms of tumorigenic transformation. The expression of circulating monocyte markers in malignant histiocytosis suggests that this tumor originates in monocytes or free histiocytes, whereas the phenotype of true histiocytic lymphoma is compatible with an origin in fixed histiocytes, which generally are devoid of the monocyte markers CD11b and CD14.     

Juvenile xanthogranuloma. Ultrastructural and immunocytochemical studies

Morphologic features of three cases of juvenile xanthogranuloma (JXG) were consistent with the current concept of a benign process, although the lesion in one case grew steadily to an extensively infiltrating large mass, which clinically suggested a malignant growth. Ultrastructurally, the lesion consisted of morphologically different developmental stages of histiocytes, probably reflecting different functional levels. An interesting finding was the presence of occasional subplasmalemmal linear densities between these cells. These densities were at times symmetrically opposed, forming desmosomelike junctional complexes. Immunohistochemical study for the presence of lysozyme, alpha 1-antitrypsin, and S100 protein by the avidin-biotin-peroxidase complex was performed in all three cases. All immunostains were negative except the positive lysozyme stain in two cases. The ultrastructural and cytochemical characteristics of histiocytes in JXG were similar to epithelioid cells in the lymph node, suggesting that JXG is a reactive lesion.     

The ultrastructure of benign and malignant fibrous histiocytomas

Five benign histiocytomas of varying pattern and three malignant fibrous histiocytomas have been studied ultrastructurally. An essentially biphasic pattern of histiocytes and fibroblasts was present. In addition fibrohistiocytes, myofibroblasts and undifferentiated cells were present in some of the tumours. The histogenesis of this group of tumours is discussed. The value of electron microscopy in establishing the diagnosis in difficult cases is emphasized, but it is not considered useful in distinguishing benign from malignant cases.     

Cytochemistry of Reed-Sternberg cells in lymph node imprints

Cytochemical reactions were examined in lymph node imprints from a group of 53 previously untreated patients with histologically proven Hodgkin's disease. In 40 of 51 cases investigated, Reed-Sternberg (R-S) cells, irrespective of the cytologic appearances and the histologic types, showed moderate to strong reactions with acid phosphatase (ACP). In 12 cases ACP activity was present in more than 25% of the R-S cells. The reaction consisted of formation of small- to medium-sized granules, which were located close to the nuclei on a diffusely positive background or irregularly distributed throughout the cytoplasm. In three cases, a coarse granular reaction product with periodic acid-Schiff was present. R-S cells were positive to the naphthol-AS acetate esterase and beta-glucuronidase reactions in four and two cases, respectively. Alkaline phosphatase and naphthol-AS-D-chloroacetate esterase reactions were completely negative. Our results have revealed a pattern of staining in the diagnostic R-S cells similar to that in its morphologic variants; this supports the view that these cells may derive from a common primitive cell. Moreover, the quality and quantity of the ACP reaction product shows that R-S cells differ from both neoplastic histiocytes of malignant histiocytosis and neoplastic lymphocytes of T-cell lymphomas. This study confirms that R-S cells lack definite cytochemical characteristics of each of supposed progenitor cells: histiocytes and T-lymphocytes.     

Utility of fine-needle aspiration in the diagnosis of panniculitis

This is a retrospective reassessment of the most important cytopathologic features of 23 FNA smears with a cytologic diagnosis of panniculitis (PN). Patients were sent by clinicians. Clinical diagnoses were as follows: 16 suspicious of PN; three cutaneous metastases of an extracutaneous primary neoplasm; four with no clinical diagnosis. Thirteen cases were subsequently submitted to histopathologic study. The following cytoarchitectural patterns were found to be very useful for the cytologic diagnosis of PN: adipocytes intermingled with foamy histiocytes, donut-like granulomas, aggregates of adipocytes intermingled with plump histiocytes, a granular basophilic background forming a lattice-like pattern, and well-formed granulomas with or without multinucleated giant cells. Inflammatory cells could be seen combined with any of these cytoarchitectural patterns. FNA does not pretend to replace excisional biopsy as the diagnostic procedure for these entities but it is a very useful diagnostic tool in certain cases: for confirming the recurrence of PN previously diagnosed by histology, for evaluating the onset of subcutaneous nodules in patients with a non-cutaneous malignant primary neoplasm, for evaluating cutaneous nodules with no clinical suspicion, and for confirming a clinical diagnosis of PN and differentiating it from other entities that mimic PN clinically. Diagn. Cytopathol. 1998;18:425–430. © 1998 Wiley-Liss, Inc.     

Morphological variability of tumour cells in T-cell-rich B-cell lymphoma

T-cell-rich B-cell lymphoma (TCRBCL) is an unusual lymphoma which is difficult to diagnose. A majority of reactive T-cells and numerous histiocytes mask the few large neoplastic B-cells. Fourteen cases of TCRBCL were studied in order to identify the main histological and cytological features useful for this diagnosis. Neoplastic cells are atypical and sometimes difficult to classify. Several types are seen; they are mostly centroblasts, which represent more than 50% of the tumour cells but are sometimes multilobated, immunoblasts- or Reed-Sternberg-like cells. Interestingly, at least two, and often three, types of tumour cell are present in all the cases. Epithelioid cells and histiocytes are always found and are often numerous. Hypervascularization and fibrosis are present in the majority of cases, but without annular bands. Necrosis is absent. All tumour cells express CD20 but EMA is expressed in less than half the cases. In two cases, the association of a diffuse large B-cell lymphoma in one site and a TCRBCL in another suggests that TCRBCL may be considered as a peculiar pattern of a diffuse large B-cell lymphoma with a strong stroma reaction. TCRBCL may not represent a clinicopathological entity.     

三种蛋白酶在恶性组织细胞增生症瘤细胞中的分布

Tumor tissues from 36 autopsy cases of malignant histiocytosis were collected for studying the distribution of lysozyme (LyS), alpha 1-antichymotrypsin (ACT) and alpha 1-antitrypsin (AT) by double peroxidase anti-peroxidase staining. The positive rates of LyS, ACT and AT were 97.14%, 91.67% and 77.78% respectively. LyS was seen mainly in the well-differentiated histiocytes. No phagocytosis was found in these cells. ACT existed in some well-differentiated histiocytes in which phagocytosis was often seen. A few atypical histiocytes also showed positive reaction to ACT. AT-positive cells were mainly atypical histiocytes and atypical multinuclear-giant-histiocytes. This study not only confirms that the tumor cels of malignant histiocytosis originate from histiocytes, but also indicates that staining of LyS, ACT and AT is useful for classification and differential diagnosis of tumor cells in malignant histiocytosis.     

Malignant histiocytosis presenting as lethal midline granuloma: immunohistological study

Recent advances in immunology have revealed that the "histiocytic" lymphoma of Rappaport is a proliferation of transformed lymphocytes rather than true histiocytes, and that the malignant cells in malignant histiocytosis (MH) are truly transformed histiocytes. We previously reported cases of MH presenting as lethal midline granuloma (MH-LMG) utilising fresh tissue specimens for the detection of cytological markers in a small number of cases. The results showed the true histiocytic nature of the proliferating cells. In this study, paraffin-embedded specimens from 16 cases with MH-LMG were processed for immunoperoxidase procedures to confirm the true histiocytic nature of the proliferating cells. Five cases with nasal and paranasal lymphomas (ML) were also stained to test the usefulness of immunoperoxidase procedures for distinguishing the MH-LMG from ML. Results were as follows; proliferating cells in MH-LMG were histiocytic in nature, staining positive for lysozyme in MH-LMG in contrast to the negative staining in ML.     

LYMPHOMATOID GRANULOMATOSIS-LIKE LESIONS IN MALIGNANT LYMPHOMA

Eighty five cases of malignant lymphoma were surveyed for the presence of angioinfiltrative and angiodestructive growth pattern of lymphold cells with areas of necrosis and granulomatous appearance simulating lymphomatoid granulomatosis (LYG). LYG-like changes were observed in 13 of 85 cases (15%). The most frequent histology was diffuse large cell lymphoma which occurred in 8 cases (4 non-cleaved, 3 cleaved, and one immunoblastic), followed by three diffuse pleomorphic lymphoma, one diffuse medium-sized lymphoma, and one Hodgkin's disease of mixed cellularity. The most frequent involving site was the lung, as well as the soft tissue. Composition of lymphoid infiltrate varied markedly from case to case and from area to area in the same case. One was solely composed of monotonous atypical cells, other pleomorphic cells including benign lymphocytes, plasma cells, leukocytes, and histiocytes with a varied number of atypical reticuloendothelial cells. The latter histologic appearance was just similar to LYG. Veins were more frequently affected than arteries. The present study indicates that, although the angioinflltrative and angiodestructive growth pattern of atypical lymphoreticular cells with granulomatous appearance is considered necessary for the diagnosis of LYG, it often occurs in malignant lymphoma. Therefore, one should consider the possibility of malignant lymphoma before making the diagnosis of LYG, especially in the specimens taken from the lung and soft tissue.     

Lymphomatoid granulomatosis-like lesions in malignant lymphoma

Eighty five cases of malignant lymphoma were surveyed for the presence of angioinfiltrative and angiodestructive growth pattern of lymphoid cells with areas of necrosis and granulomatous appearance simulating lymphomatoid granulomatosis (LYG). LYG-like changes were observed in 13 of 85 cases (15%). The most frequent histology was diffuse large cell lymphoma which occurred in 8 cases (4 non-cleaved, 3 cleaved, and one immunoblastic), followed by three diffuse pleomorphic lymphoma, one diffuse medium-sized lymphoma, and one Hodgkin's disease of mixed cellularity. The most frequent involving site was the lung, as well as the soft tissue. Composition of lymphoid infiltrate varied markedly from case to case and from area to area in the same case. One was solely composed of monotonous atypical cells, other pleomorphic cells including benign lymphocytes, plasma cells, leukocytes, and histiocytes with a varied number of atypical reticuloendothelial cells. The latter histologic appearance was just similar to LYG. Veins were more frequently affected than arteries. The present study indicates that, although the angioinfiltrative and angiodestructive growth pattern of atypical lymphoreticular cells with granulomatous appearance is considered necessary for the diagnosis of LYG, it often occurs in malignant lymphoma. Therefore, one should consider the possibility of malignant lymphoma before making the diagnosis of LYG, especially in the specimens taken from the lung and soft tissue.     

Sinus histiocytosis with massive lymphadenopathy and malignant lymphoma involving the same lymph node: a report of four cases and review of the literature.

Sinus histiocytosis with massive lymphadenopathy (SHML), also known as Rosai-Dorfman disease, is a disorder of unknown cause. Rarely, patients with SHML also have malignant lymphoma, usually involving anatomic sites different from those involved by SHML We report four patients in whom SHML and malignant lymphoma were identified in the same lymph node biopsy specimen. The SHML in each case was present as a small focus, less than 1 cm. Immunohistochemical studies showed that the abnormal histiocytes were positive for S-100 and negative for CD1a. The malignant lymphomas included two cases of follicular lymphoma and two cases of Hodgkin's disease, nodular lymphocyte predominant type. The presence of SHML in these patients did not impact clinical decisions, and there was no evidence of SHML elsewhere. Thus, the presence of focal SHML associated with malignant lymphoma in these cases was an incidental histologic finding that seems not to have had any clinical significance.     

An immunohistochemical study of differentiation in malignant fibrous histiocytoma

Immunohistochemistry was used to examine 10 cases of malignant fibrous histiocytoma. Malignant cells in all cases expressed vimentin and in eight there was co-expression of either desmin or neurofilament, both of these being present in four cases. In addition, cytokeratin was found in one case. In each tumour, a population of small cells was identified which had the staining characteristics of benign macrophages, and this was distinct from the tumour cells. This study supports the concept that malignant fibrous histiocytoma is a tumour of mesenchymal cells rather than of histiocytes and emphasizes the diversity of its cytostructure.     

Ultrastructure of malignant histiocytoma arising in the acromion.

The ultrastructural features of a malignant histiocytoma of the acromial process of the scapula were studied. Material was obtained from two surgical biopsy specimens and an amputation specimen from the tumor. Cells possessing characteristics of histiocytes, fibroblasts, xanthoma cells, and multinucleated giant cells were present throughout the tumor. Smaller numbers of undifferentiated cells and lymphocytes were also observed. Intimate cytoplasmic interdigitations between adjacent tumor cells were found, and instances of degenerating intracytoplasmic cells, possibly representing phagocytosis, were observed. Specimens stained with periodic acid-Schiff reagent with and without exposure to diastase, examined by light microscopy, showed that numerous cells contained phagocytized material consisting of degenerating cells rather than cytoplasmic glycogen. Intraumor lymphocytes apparently represented an inflammatory reaction to the tumor. The tumor giant cells and xanthoma cells were probably modified histiocytes. Results of the study were compared with previous reports of ultrastructural studies of malignant histiocytoma of soft tissues. Fundamental similarities between such studies and this one suggested that the progenitor cell is a histiocyte, whether arising in bone or in soft tissues, and that the progenitor cell is capable of differentiation in both histiocytic and fibroblastic directions.     

Malignant histiocytosis: a study on clinicopathological features and cell origin]

Thirty-one autopsy cases previously diagnosed as malignant histiocytosis (MH) were studied by means of immunohistochemical staining. Antibodies detecting the formalin resistant epitopes on T-cells, B-cells and those of histiocyte/monocyte origin were used. It was shown that the malignant histiocytes reacted only to the cell markers derived from histiocyte/monocyte, and only a part of lymphocytes showed positive reaction to the T and B cell markers. It is suggested that the histiocyte/monocyte lineage is the possible origin of the malignant proliferating cells in MH. The clinicopathological features and the differentiation of MH from familial erythrophagocytic lymphohistiocytosis, virus-associated hemophagocytic syndrome and malignant lymphoma are described. The pathogenesis, the causes of death and the points for attention in the treatment of MH are also discussed.     

Spontaneous regression of metastatic malignant melanoma in 2 sibs with xeroderma pigmentosum.

The clinical and pathology findings in 2 sibs with xeroderma pigmentosum (XDP), complicated by metastatic malignant melanoma which underwent spontaneous regression, are described. The pathology of one of these patients showed features of possible spontaneous regression, namely foamy histiocytes, capillary proliferation, and a chronic inflammatory infiltrate which was devoid of malignant cells, suggesting the possibility that an immunological mechanism was at work. It was of interest that a recent review of 27 cases of spontaneous regression of metastatic melanoma since 1900 contained a patient with XDP. Adding our 2 cases, at least 10% of the spontaneous regressions of metastatic melanoma occurred in patients with XDP. This unusual association raised the question that the genotype for XDP may possibly foster control of metastatic malignant melanoma in some as yet unknown way.