Edwin Kaiserling

Diagnostic value of immunostaining for tryptase in patients with mastocytosis

The term mastocytosis is used to describe a heterogeneous group of disorders characterized by abnormal growth and accumulation of mast cells (MCs). Cutaneous and systemic variants exist. Systemic mastocytosis may show an indolent or malignant clinical course. In malignant mastocytosis (MM), the diagnosis often is missed because the MCs are morphologically abnormal and lack metachromatic granules or the underlying histologic picture is complex. The cytoplasmic serine protease tryptase is produced by MCs and is thought to be expressed at all stages of MC maturation. To assess the diagnostic value of tryptase staining in mastocytosis, tissue sections from 93 patients with mastocytosis, including MM (n = 37), systemic indolent mastocytosis (n = 47), urticaria pigmentosa (n = 5), MC leukemia (n = 2), and solitary skin mastocytoma (n = 2) were stained with the antitryptase antibody G3. The results were compared with those of Giemsa and chloroacetate esterase (CAE) staining. Using antitryptase antibody G3, MC infiltrates were identified in all patients examined, including those with MM (37 of 37), and virtually all the neoplastic MCs (> 95%) appeared to react with G3. In MM, significantly fewer MCs were positive in Giemsa (54.5%; p < 0.05) and CAE (78.8%; p < 0.05). Moreover, G3 produced clear diagnostic staining in all cases of MM, but the proportion of cases with clear diagnostic results (> 10% of neoplastic cells positive) was considerably lower with Giemsa (48.6%; p < 0.05) and CAE (75.7%; p < 0.05) staining. By contrast, tryptase, Giemsa, and CAE produced diagnostic staining of MCs in virtually all cases of systemic indolent mastocytosis, urticaria pigmentosa, and solitary skin mastocytoma. In systemic mastocytosis, survival was significantly reduced in cases with Giemsa-/tryptase+ or CAE-/tryptase+ tumor cells compared to those cases with Giemsa+ or CAE+ MC infiltrates (p < 0.001).

Liver findings in generalized mastocytosis. A clinicopathologic study

Although the liver is one of the four organs most often involved in generalized mastocytosis (GM), little is known about macroscopic and microscopic liver findings in this rare disease. This study included 182 patients with GM (confirmed in most by bone marrow histologic study), comprising 52 cases of our own and 130 reported in the literature. Hepatomegaly was found in 131 (72%) of the 182 patients, cirrhosis in seven (4%), and periportal fibrosis in 25 (14%). Mast cell (MC) infiltration of the liver was confirmed histologically in 77 (42%). Liver specimens were available for further histologic investigation in 11 of our own cases of GM. Nine of these contained MC aggregates. Mast cells were found predominantly in the portal tracts but numerous MC also were loosely scattered throughout the sinusoids. Diagnostic confusion of GM with reactive lesions of the liver is unlikely to occur since MC, according to our own observations and the available literature, are found only in very low numbers in normal liver tissue, where they occur mainly in the portal tracts. Reliable identification of MC does, however, require special stains, like Giemsa, toluidine blue, or naphthol AS‐D chloroacetate esterase.

Mast cell sarcoma of the larynx.

A 74 year old woman presented with a primary subglottic tumour. Neither cutaneous mastocytosis (urticaria pigmentosa) nor spread to the bone marrow, liver, or spleen were detected. About two years after initial manifestation of the tumour nodular skin metastases appeared, as well as local recurrence in the larynx. Despite chemotherapy and radiation the disease progressed and was fatal. The terminal phase was characterised by generalisation of the mast cell tumour with diffuse infiltration of bone marrow and, shortly before death, leukaemic transformation. The patient died four years after onset of disease with symptoms of a hemorrhagic diathesis. As far as we know this is the first case of mast cell sarcoma to be reported in man.

Lymphoid cells and tissue mast cells of bone marrow lesions in systemic mastocytosis: a histological and immunohistological study

Systemic mastocytosis (SM) can be regarded as a tumorous proliferation of tissue mast cells (TMC) involving various organs, particularly the bone marrow. The infiltrates, however, are by no means composed exclusively of TMC, but also contain eosinophils and lymphocytes. The varying composition of the TMC infiltrates and the immunohistological characteristics of the lymphatic cells were the main subjects of investigation in this study.

Spleen findings in generalized mastocytosis. A clinicopathologic study

Background. Little information regarding the morphologic findings of the spleen in generalized mastocytosis (GM) is available and no comprehensive review of the literature on this subject has been published.

The decidua of early human pregnancy: immunohistochemistry and function of immunocompetent cells.

Like the endometrial stroma, the decidua contains lymphoreticular cells, and these are probably involved in immunological interactions between the conceptus and the mother. Lymphoreticular cells in decidual tissue obtained from 12 patients undergoing therapeutic abortion of an intact pregnancy at 6-10 weeks gestation were investigated in this study. Immunophenotyping with a broad panel of monoclonal antibodies revealed various subpopulations of lymphoreticular cells. Macrophages (Ki-M6+, Ki-M7+, Ki-M8+, KP1+, MAC 387+ and Ki-M1P+) represented the largest fraction of intradecidual lymphoreticular cells. CD3+ and CD8+ lymphocytes were found in moderate numbers and CD4+ cells in small numbers. The majority of the intradecidual lymphoid cells exhibited an unusual phenotype [CD7+, CD2+, CD56+, triple negative (CD3-, CD4-, CD8)]. The distribution of these unusual lymphocytes mirrored that of the so-called endometrial stromal granulocytes. A few of these stromal granulocytes reacted with the macrophage-associated antibody KP1, but not with Ki-M1P, another macrophage marker. This was confirmed by immuno-electron microscopy. The finding that intradecidual CD3+ lymphocytes express neither the alpha/beta nor the gamma/delta heterodimer of the T cell antigen receptor was unexpected. However, these cells did express the alpha/beta heterodimer after in vitro culture with PHA-P and recombinant exogenous interleukin-2. No stimulated T lymphocytes expressing activation antigens could be detected. B lymphocytes, T and B immune accessory cells and CD15+ granulocytes were found only in small numbers or were absent. Amongst cells expressing NK cell markers, CD57+ and CD16+ cells were found in small to moderate numbers, while CD56+ cells were detected in large numbers.(ABSTRACT TRUNCATED AT 250 WORDS)

Solitary mastocytoma of the eyelid. A case report with special reference to the immunocytology of human tissue mast cells, and a review of the literature.

Solitary mastocytoma (mast cell naevus) of the skin represents a relatively rare dermal tumour. Its occurrence on the lower eyelid is exceptional. We report the case of a 4 month old male infant who exhibited a firm, yellowish nodule (1 cm in maximum diameter) on the lower lid of the right eye from birth. Histologically, the tumour consisted of strongly metachromatic tissue mast cells (TMC) infiltrating the whole dermis, the adjacent subcutaneous tissue and the lid muscle. Since comparable skin lesions in other sites were not observed, a diagnosis of solitary mastocytoma was made. Immunocytological investigations revealed strong reactivity of the TMC to antisera against vimentin, common leucocyte antigen (CLA),α1-antitrypsin (α1-AT) and α1-antichymotrypsin (α1-ACT). A minor proportion of the TMC reacted to antisera against lysozyme and KiB3. Surprisingly, the TMC also reacted to antisera against certain regulatory peptides (RP), namely adrenocorticotropic hormone (ACTH), peptide histidine isoleucine (PHI), leu-enkephalin and met-enkephalin. However, absorption controls revealed that the immunostaining for ACTH and the two enkephalins was non-specific. The immunocytological phenotype of TMC suggests a close relationship to the myeloid-monocytic lineage, but a possible relationship between TMC and the diffuse neuroendocrine system needs further investigation.

Expression of cell adhesion molecules by endothelium in the human lower uterine segment during parturition at term

OBJECTIVEnOur purpose was to determine whether the expression of certain adhesion molecules by endothelium in the human lower uterine segment at term varies with the degree of cervical dilatation.nnnSTUDY DESIGNnBiopsy specimens of the lower uterine segment of 34 women undergoing cesarean section at term at various stages of cervical dilatation were immunostained for endothelial leukocyte adhesion molecule-1, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and platelet-endothelial cell adhesion molecule.nnnRESULTSnThe expression of endothelial leukocyte adhesion molecule-1 was significantly greater at more than 6 cm dilatation than at less than 2 cm (p = 0.00031) as was that of vascular cell adhesion molecule-1 (p = 0.033). Expression of intercellular adhesion molecule-1 and platelet-endothelial cell adhesion molecule did not vary with the degree of cervical dilatation.nnnCONCLUSIONnCervical dilatation is associated with up-regulation of certain endothelial cell adhesion molecules. The findings support the hypothesis that certain processes associated with cervical dilatation at term resemble those involved in the acute inflammatory reaction.

Melanin-containing hepatoblastoma with endocrine differentiation : an immunohistochemical and ultrastructural study

Background. The authors previously have reported that hepatoblastomas may exhibit endocrine differentiation. This report describes a hepatoblastoma in which a melanocytic component was present in addition to endocrine differentiation.

Acute myeloid leukemia : immunohistologic findings in paraffin-embedded bone marrow biopsy specimens

Immunohistochemical investigations were performed on decalcified, paraffin-embedded iliac crest trephine biopsy specimens from 30 cases of acute myeloid leukemia (AML, as defined by the FAB classification) with antibodies against B cells (L26, 4KB5, MB1, Ki-B3), T cells (UCHL1, MT1), myeloid/histiocytic cells (anti-neutrophil elastase, MAC387, anti-S-100 protein, anti-alpha 1-antichymotrypsin, DAKO-M1), natural killer/killer cells (anti-Leu-7), and megakaryocytes (anti-factor VIII-related antigen). (1) The blast cells of all the cases reacted with from at least two to at most eight different antibodies. Each antibody reacted with blast cells in a minimum of two (maximum 30) cases. (2) MT1, Ki-B3, anti-alpha 1-antichymotrypsin anti-neutrophil elastase, anti-S-100 protein, and MAC387 stained blast cells in more than 50% of the cases; MB1, L26, UCHL1, 4KB5, and DAKO-M1 in 20% to 50% of the cases; and anti-Leu-7 and anti-factor VIII-related antigen in less than 20% of the cases. (3) In the majority of cases many T lymphocytes, a small-to-moderate number of B lymphocytes, and a few Leu-7-positive lymphoid cells were intermingled with the blast cells. In some cases, especially where only a minor proportion of the blast cells was immunostained, it was nearly impossible to distinguish the lymphocytes of the tumors stromal reaction from small blast cells. Thus, AML exhibits a heterogeneous immunophenotype in trephine biopsy specimens. Immunohistologic diagnosis of this disease in such specimens may be extremely difficult. Since staining of the blast cells with one or more of the antibodies generally used to define B cells, T cells, or their neoplastic derivatives is not uncommon, misinterpretation as non-Hodgkins lymphoma of high-grade malignancy could easily occur. These findings also suggest that mixed-type (hybrid) acute leukemias with coexpression of myeloid and lymphoid cell markers could be more common than generally realized.