cf also bones neoplasms
The real case. A patient comes to us for a normochromic normocytic anemia, that isn't due to iron loss, such as a classic sideropenic anemia or microcytic anemia but it's characterized by myelodysplasia. The investigation of the case is started. In the standard CRX, "nummular lesions" are highlighted, which are such as 10 cent coins, visualized on on both the humeri, as if they were "repetitions", ie metastases. It seems that the bone is worm-eaten, full of osteolytic areas. Let's go, immediately, to look at the prodidogramma: the diagnosis is soon made, it is a striking case of Myeloma Multiplo. It is an affection that derives from the proliferation of a single clone of neoplastic cells of B-lymphocyte nature, differentiated, so to speak, in a plasma cellular sense, with infiltration of the same cells in the bone marrow, spleen, liver. These myelomatous elements produce a monoclonal immunoglobulin called M protein and / or light chains that can be found in urine as Bence Jones proteins.
The disease affects individuals aged 60 and constitutes 10% of all neoplasms of
haematological relevance;
An etiology of prolonged exposure to ionizing radiation has been demonstrated, ie, in radiology personnel, among the survivors of Hiroshima and Nagasaki; it is also believed that chromosomal alterations are at the base of this neoplasm, e.g. trisomies 3, 5,7,9,11 or chromosomal rearrangements 1 and 14; presence of a higher expression of the HLA B5 locus; increased expression of the c-myc oncogene and mutations of the proto-oncogene ras. Finally, there are cases of multiple myeloma among personnel who came into contact with asbestos (asbestos), pesticides, petroleum derivatives. The onset of the pathology is subtle; for our experience, a pazient of about 65 years, came to our observation by chance, for a not well-defined bronchopneumopathy, presented for about 10 years and other symptoms such as episodes of edema in the lower limbs, pleural effusion, bone pain and dyspromidemic state, with significant reduction in values albumin and increase in the fraction of gamma globulins with monoclonal peak. He was suffering from febrile episodes, asthenia, and slimming.
A radiological survey of the skull showed osteolytic areas and, as well, there were further areas of osteolysis on the vertebral column, pelvis and ribs, presence of confluent pulmonary opacifications as interstitial infiltrates. From the laboratory investigation, on the basis of the finding of normocytic anemia and of monoclonal gammapathy and on the basis of the Rx finding, diagnosis was made and treatment with melphan was undertaken. The skeletal of these subjects presents bone deformities and is subject to pathological fractures, even for costal, femoral, vertebral crushing. An anemic syndrome is present in these subjects due to infiltration of the marrow by myelomatous neoplastic elements and also for renal insufficiency and myelotoxic action of the drugs. Hyperdisprotidemia, hypercalcemia, elevated ESR is also present.
Infections for neutrophil deficiency and for the presence in the circulation of
neoplastic plasma cells that secrete immunoglobulins without effect; among the
infections there are streptococcus pneumoniae pneumoniae, staphylococcus aureus,
pneumocystis carinii.
Haemorrhages: epistaxis, gingivorrhagia, retinal hemorrhage due to platelet drop
and coagulation abnormalities probably related to the fact that M proteins
interact via the Fab fragment with fibrin monomers, so that the clot becomes
gelatinous, with scarce fibrous supports and does not retracts. Furthermore,
coagulation factors decrease, probably due to myelomatous infiltration of the
liver, which is the main site of their synthesis.
Effects of increased blood viscosity: epistaxis, headache, sensory disturbances
up to paraproteinemic dulling.
Deposition of amyloid and heart failure, nephrosis and steatorrhea.
Kidney: Bence Jones hypercalcemia and proteinuria, recurrent pyelonephritis,
obstructive tubulopathy.
Nervous system: root pains due to root compression and spinal transverse lesions.Cefalea,
deafness, nystagmus, radiculovitis.
Major diagnostic criteria: bone marrow biopsy with giant plasma cells greater
than 30%, Mott cells; B) Serum M protein rate greater than 3.5 grams / dl for
IgG,> 2 g / dl for IgA. C) Bence Jones proteinuria greater than 1 gram / 24
hours for kappa or lambda chains.
Minor criteria: A) plasmocytosis of the marrow between 10-30%; B) osteolytic
lesions C) anemia D) reduction of IgG, IgA and IgM values.
The pathology presents a staging for the prognosis; the most accepted staging is
that of Durie and Salmon which is based on the criteria of anemia,
hypercalcaemia, skeletal injury and M protein.
STAGE I: Hemoglobin> 10 grams / dl; Normal calcemia; Rx skeleton at most with
only one injury; low production of Protein M: IgG <5 g / dl; IgA <3 g / dl; M
proteinuria <4 grams / 24 hours.
STAGE II: internmedio
STAGE III: hemoglobin <8.5 g / dl; calcemia> 12 mg / 100 ml; numerous osteolytic
lesions; production of proteins M: IgG> 7 g / dl; IgA> 5 g / dl; M proteinuria>
12 grams / 24 hours.
It uses chemotherapy. The classic scheme includes the use of Melphalan (6 mg / m2) + Prednisone (60 mg / m2) for 7 days per month or other alkylating agents such as cyclophosphamide and nitrosuree, but since the 1980s schemes combined with adriamates have been introduced, vincristine and dexamethasone (VAD) or vincristine cyclophosphamide, melphalan, cyclophosphamide and prednisone. The intent is to achieve a remission with a 50-76 reduction of the M protein to values <25 g / l in two measurements at 4 weeks; reduction of B.J. with values of 0.2 g / 24 hours and absence in the progression of bone lesions with normalization of calcemia. Over the last few years, hope has been given by the transplantation of autologous and allogeneic marrow, after ablative therapy, by the infusion of peripheral stem cells and other hematopoietic growth factors (G-CSF and GM-CSF). The advice of Gastroepato is, therefore, to turn to specialized Centers and to start well and soon with the appropriate therapies, not underestimating the risk of infectious complications that, for our experience, are the order of the day including the heavy side effects of chemotherapies.
Waldenstrom's Macroglobulinemia (MW) is a neoplastic proliferation with a "lymph-plasma-cellular"
morphology, which synthesizes monoclonal immunoglobulins of the IgM class, by
neoplastic transformation of a lymphocytic B-cell; the symptomatology is subtle,
with asthenia, adynamia, dyspnea, due to an infiltrative syndrome with
hepatosplenomegaly and hemorrhagic syndrome, with mucosal bleeding and
hyperviscosity due to a high rate of IgM molecules; to this are added, as for
Myeloma Multiplo, infectious complications. The IgM groups together to form
tetrameric complexes with a molecular weight of 1,000,000, responsible for
hyperviscosity. The diagnosis makes use of the study of the bone marrow biopsy
which is characterized by plasmacellular elements; in addition we will have
Bence Jones proteinuria due to kappa chains, and erythrocyte rouleaux, ie
erythrocytes stacked on the slide.
Cryoglobulins are antibodies that precipitate and gel monoclonal:
IgM, IgG, IgA, Bence Jones chains
mixed, Igm + IgG
polyclonal, more proteins
They are due to abnormal production of proteins in the course of multiple
myeloma, macroglobulinemia, lymphoproliferative diseases, or they can be found
in the course of SLE, rheumatoid arthritis, allergic vasculitis, Sjogren's
syndrome; if the presence of crioglubine is suspected it is necessary to leave
the serum of a blood sample first in a water bath at 37 ° and then at 4 °: at
this point a precipitate will be observed, criocrito. Cryoglobulins are
responsible for Raynaud's phenomenon, namely the circulatory slowing of the
extremities and the frogor vasospasm of the fingers, tip of the nose, ear lobes,
etc., and of hives in frigore.