Anatomical Society Symposium on extramedullary haematopoiesis

A symposium on extramedullary haematopoiesis was held on 11–12 September 1996 at the University of St Andrews. The following are abstracts of papers and posters presented at the meeting.     

Embryonic stem cell-derived haematopoiesis

Embryonal stem (ES) cells are pluripotent cell types that in chimaeric mice can give rise to all cellular lineages. Early studies showed that they also had the potential to form mature erythrocytes following in vitro differentiation. In recent years ES cells have been demonstrated to be competent both to produce all haematopoietic lineages following in vitro differentiation and long-term repopulating haematopoietic stem cells. This review discusses the approaches that have been used to produce these haematopoietic cells and the nature of the haematopoietic stem cells that can be isolated. The utility of the system to both isolate genes involved in control of haematopoiesis and to assess their function following transgenesis is demonstrated. The prospectives for this field are then discussed in the context of recent developments in human ES cells and evidence of stem cell plasticity.     

Splenic T helper cell type 1 cytokine profile and extramedullary haematopoiesis in severe combined immunodeficient (scid) mice with inflammatory bowel disease (IBD)

Scid mice develop a severe, chronic, and lethal IBD 3–6 months after engraftment of gut wall from immunocompetent congenic donors, induced by donor-derived CD4⁺ T cells migrating from the graft [ 7]. We have investigated intracellular T-helper type 1 (Th1) cytokines in the spleens of gut wall-transplanted scid mice with IBD. Increased fractions of interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α) and IL-2-positive CD4⁺ T cells were found in the spleens of diseased mice compared with control mice. Moreover, a small but significant population of CD4⁺ T cells which stained positive for granulocyte-macrophage colony-stimulating factor (GM-CSF) was found in scid mice with IBD but was virtually absent in congenic non-scid control mice. Cloning of granulocyte/macrophage colony-forming cells (G/M-CFC) revealed that both non-transplanted scid mice and scid mice with IBD had an 8–14-fold increase in splenic G/M-CFC compared with control mice. No significant difference in the number of G/M-CFC per total spleen was found between non-transplanted and disease scid mice, although both groups of mice showed a nearly two-fold increase compared with control mice. G/M-CFC were never found in the thymus, liver or lymph nodes of diseased mice. Immunohistochemistry revealed that the multinucleated giant cells observed in the gut wall of diseased mice did not represent haematopoietic foci, but were derived from macrophages. These observations point towards a dominant role for Th1-type CD4⁺ T cells in the immunopathogenesis of IBD, whereas haematopoiesis does not seem to be affected by the development of the disease.     

Extramedullary haematopoiesis in massive hepatic necrosis

AIMS: To determine the frequency of extramedullary haematopoiesis (EMH) in massive hepatic necrosis (MHN). METHODS AND RESULTS: Explanted livers of 11 adult patients transplanted consecutively for MHN were examined histologically and immunohistochemically for the presence of EMH. The aetiology of the liver damage was unknown in seven cases and drug induced in four. The presence of stem cell markers (CD34, c-kit), erythroid precursors (glycophorin A), myeloid precursors (myeloperoxidase) and megakaryocyte precursors (CD31) was investigated by immunohistochemistry. Erythroid, myeloid and megakaryocyte precursors were observed in all cases. Morphologically, haematopoietic blast cells were clustered in areas of collapse, separating islands of regenerating ductules and scattered between ductules, in a similar distribution to immunohistochemically identified c-kit-positive putative stem cells. No CD34+ cells other than endothelial cells were seen. All 11 patients were anaemic at the time of transplantation. CONCLUSIONS: EMH is a frequent finding in patients undergoing liver transplantation for MHN. This may be a consequence of the anaemia associated with this condition. Alternatively, the possibility that intrahepatic haematopoiesis is linked with hepatopoiesis is an additional, intriguing possibility that deserves further study.     

Plasmablastic extramedullary plasmacytoma

Extramedullary plasmactyoma is the solitary, soft tissue form of plasma cell neoplasm but lack the defining features of medullary or multiple myeloma. The diagnosis is difficult to make in routine practice setting due to the morphological and immunohistochemical overlap with plasmablastic lymphoma. We report a case of plasmablastic extramedullary plasmacytoma in a 52-year-old in the mandibular lingual gingiva and discuss its differential from plasmablastic lymphoma. The gingival mass regressed with primary radiotherapy.     

Extramedullary haematopoiesis in the thyroid gland

The case of an 82-year-old female patient with extramedullary haematopoiesis in the thyroid gland due to agnogenic myeloid metaplasia is reported.     

A stochastic model for haematopoiesis in cats

Haematopoiesis is the process by which progenitor cells differentiate into competent mature blood cells. Only those cells in the latter stages of haematopoiesis can be observed in vitro, so theories about the early stages of the process cannot be tested directly. Experimental data of bone marrow samples from Safari cats provides evidence for the clonal succession hypothesis of early haematopoiesis. In this paper, a hidden Markov model is constructed to quantify this support. Recursive updating techniques are derived and are used to calculate the likelihood and to construct fitted values for the model. Inference is based on multimodal likelihood surfaces.     

Intraocular Myeloma

Abstract

An eighty-seven year old female presented with complaints of pain in the left eye. She had a history of chronic open angle glaucoma that was under control with medication. She had lost all vision, and the eye had become very painful and inflamed. She was admitted with a diagnosis of endopthalmitis. Enucleation was performed and inspection of the specimen revealed a firm globe with a white mass extending over the iris and across the pupil in the anterior chamber. Microscopic evaluation with the hematoxylin and eosin stain revealed a plasma cell infiltrate involving the ciliary process, extending into the posterior chamber, occlusion of the retinal artery, and extensive loss of nerve fibers within the optic nerve. An accumulation of a pinkish and somewhat fibrillar material within the tumor and optic nerve was also observed. Stains for myelin and amyloid and a methyl green pyronine were performed, and immunoperoxidase for IgG, IgA, IgM, kappa and lambda.     

Sclerosing extramedullary hematopoietic tumor

A 73-year-old woman presented with abdominal pain, weakness, and weight loss. Pertinent medical history included myelofibrosis, severe anemia, and lumpectomy for breast cancer. Computed tomography showed marked splenomegaly and numerous soft tissue masses in the mesentery. Excisional biopsy of the mass showed an encapsulated tumor with yellow-tan nodular growth pattern. Microscopically, the tumor was characterized by the presence of bizarre giant cells in background of prominent dense fibrous stroma. The atypical giant cells were positive for FVIII antibody staining. Many other cells were positive for CD43 antibody staining, indicating that the tumor was hematopoietic in nature, so-called sclerosing extramedullary hematopoietic tumor. Extramedullary hematopoiesis is a common phenomenon associated with severe anemia of any cause. When associated with myelofibrosis, however, it has different morphology from extramedullary hematopoiesis of the other causes. The significance of recognizing sclerosing extramedullary hematopoietic tumor is that it is often mistaken for sarcomas and other malignant neoplasms, especially when the clinical history is unknown.     

Intraocular medulloepithelioma

Intraocular medulloepithelioma is a congenital tumor of the ciliary epithelium that typically presents during the first decade of life. The histologic diagnosis is based on characteristic ribbons of pseudostratified neuroepithelium admixed with loose mesenchymal tissue rich in hyaluronic acid, vaguely resembling developing retina and vitreous. More than a third of medulloepitheliomas contain heteroplastic tissue, which in some cases makes up most of the tumor. Malignant medulloepitheliomas consist of a proliferation of neuroblasts, which in areas can be indistinguishable from retinoblastoma. Unlike its highly malignant counterpart in the central nervous system, intraocular medulloepithelioma has a good prognosis as long as tumor has not spread beyond the eye. Definitive diagnosis and eye-conserving therapy is possible with fine-needle aspiration biopsy. The histologic differential diagnosis of medulloepithelioma is broad, ranging from retinoblastoma and sarcoma to ciliary epithelial adenoma and adenocarcinoma.     

Intraocular Myeloma

Abstract

An eighty-seven year old female presented with complaints of pain in the left eye. She had a history of chronic open angle glaucoma that was under control with medication. She had lost all vision, and the eye had become very painful and inflamed. She was admitted with a diagnosis of endopthalmitis. Enucleation was performed and inspection of the specimen revealed a firm globe with a white mass extending over the iris and across the pupil in the anterior chamber. Microscopic evaluation with the hematoxylin and eosin stain revealed a plasma cell infiltrate involving the ciliary process, extending into the posterior chamber, occlusion of the retinal artery, and extensive loss of nerve fibers within the optic nerve. An accumulation of a pinkish and somewhat fibrillar material within the tumor and optic nerve was also observed. Stains for myelin and amyloid and a methyl green pyronine were performed, and immunoperoxidase for IgG, IgA, IgM, kappa and lambda.