Special Pathology 3 страница

Clinical picture. The onset of the disease is in most cases acute or subacute: high temperature (remittent or hectic), profuse sweating, chills, pronounced weakness, pain in the bones, and other general symptoms resembling those of acute septic affections. Pain in the throat is often one of the first complaints: swallowing becomes painful because of necrotic ulceration of the throat and fauces. For this reason the disease is often mistaken for necrotic tonsillitis and only further observation of the patient and the study of the bone marrow and blood help the physician establish a correct diagnosis. Fever, chills and sweating, which are so characteristic of acute leucosis, are explained by the pyrogenic effect of purines released in great quantity during the decomposition of immature leucocytes. Fever can also be caused by secondary infections; despite the markedly increased pro­duction of white blood cells, their function is inadequate, and resistance of leucosis patients to various infections decreases.

In some cases the onset of the disease is gradual, with non-pronounced general symptoms: slight weakness, indisposition, rapid fatigue, and subfebrility. The condition then worsens and a complete clinical picture of the disease develops. Anaemia and various haemorrhagic complications and secondary infection develop.

Inspection of the patient usually reveals grave condition from the very onset of the disease. In the terminal period the condition is particularly grave: the patient is passive, answers the doctor's questions with difficulty, or is unconscious. The skin is pallid, sometimes with yellowish or greyish hue, and moist; its turgor is decreased. Traces of subcutaneous and in-

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Chapter 9. Diseases of the Blood

tracutaneous haemorrhages can be seen. The tourniquet and the pinch tests are positive; haemorrhage is considerable at points of injections. Necrosis and bed-sores are possible. Necrosis of the mucosa, especially of the mouth and throat, is especially pronounced. Ulcerous and necrotic tonsillitis, gingivitis, and stomatitis are quite characteristic of the disease. Necrotized surfaces are covered with a poorly removable grey or yellowish coat. When removed, it reveals bleeding ulcers. The breath of the patient is putrefac­tive. Palpation reveals enlargement of separate groups of the lymph nodes, spleen, and the liver. The heart borders are broadened; tachycardia, systolic murmur at the heart apex (due to dystrophic processes in the heart muscle), and anaemia are revealed. Pericarditis and pleuritis are possible. Each haematological form of leucosis is characterized (though not necessarily) by some special clinical features.

The blood of parents contains increased number of white blood cells: to 1 x 10¹¹ and even 2 x 10^u per 1 1 (in rare cases even this figure may be exceeded) (Plate 32). Subleukaemic forms of the disease can occur. Leucopenia can develop in some cases at the early stage of acute leucosis. Leucopenia is then succeeded by leucocytosis. The most specific haematological sign of the disease is the presence of blast cells in the peripheral blood. All blast cells are similar morphologically but special cytochemical reactions can be used to differentiate between them. Prevalence of their certain forms is determined by the haematological variant of leucosis (acute lymphoblastic, acute myeloblastic, acute monoblastic leucosis, etc.). The immature forms may amount to as high as 95 and even 99 per cent. Leukaemic cells often have some specific defects in their nuclear and cytoplasmic structure. Only the youngest and the most mature cells can be revealed in the blood of most patients with acute leucosis, while intermediate forms are absent (hiatus leucaemicus). Eosinophils and basophils are absent; other cell forms are decreased significantly not only relatively but also absolutely. Thrombocytopenia and anaemia are observed which can be explained by the displacement of megakariocytes and erythroblasts from the bone marrow by vigorously proliferating blast cells and also by the prevalent development in the direc­tion of leucopoiesis. Anaemia may intensify due to haemorrhage (characteristic of this disease) and also due to the intensified haemolysis of erythrocytes. Coagulability of blood and the bleeding time are abnormal in most cases; ESR sharply increases.

The bone marrow punctate contains 80-90 per cent of leukaemic blast cells, which displace all other cell elements.

Course. The course of the disease is progressive. Prognosis is un­favourable. The average life expectancy of patients with acute leucosis is about 2 months; in separate cases from 2 days to 18 months. But modern

therapy can prolong the patients' life to 2-3 years; in rare cases to 5 years and more.

Treatment. Combined therapy, including 3-5 preparations, depends on the clinico-haematological variant of the disease. Corticosteroids (e.g. prednisolone) in large doses are prescribed together with cytostatic (6-mercaptopurin, vincristin, methotrexate, etc.). Anaemia is removed by blood transfusion and by preparations preventing haemorrhagic complica­tions (vicasol, calcium chloride, aminocaproic acid). If secondary infection arises, antibiotics are indicated. Intense vitamin therapy is also useful.

CHRONIC MYELOLEUCOSIS

Chronic myeloleucosis is the most common variety of leucosis. It develops from precursors of myelopoiesis. It is characterized by myeloid hyperplasia of the bone marrow attended by delayed maturation of the myeloid elements at a certain stage of their development and by myeloid metaplasia of the spleen, liver, lymph nodes and other organs. Karyological studies reveal, in the overwhelming majority of cases, the so-called Philadelphia (Ph¹) chromosome in the myeloid precursors. Chronic myeloleucosis occurs at any age but its incidence at the age of 20-45 is higher.

Pathological anatomy. The internal organs are pallid and anaemic. The spleen is marked­ly enlarged, consolidated; it has traces of past ischaemic infarctions and new infarctions. Microscopy does not reveal spleen follicles; diffuse proliferation of the myeloid tissue can be seen. The liver is enlarged and myeloid proliferation can be traced by the course of the liver capillaries and the periportal layers. The lymph nodes are somewhat enlarged; their section is greyish-red. Myeloid tissue can be seen in them (as well as in the other organs).

The bone marrow is juicy, bright-red or greyish-red; it displaces fat marrow in the tubular bones to a lesser or greater extent. Red bone marrow is represented mainly by the myeloid elements; the more acute the process, the greater the prevalence of less differentiated elements.

Clinical picture. The initial symptoms of the disease are not specific: weakness, fatigue, excess sweating, and subfebrile temperature. The symp­toms become more pronounced with time and the patient consults a doc­tor. The work capacity decreases appreciably, weakness increases, sweating becomes profuse, the body temperature rises periodically to 37.5—39 °C; cachexia develops. A common symptom is the feeling of heaviness in the left part of the abdomen which depends on the pronounced enlargement of the spleen. Pain may be due to a considerable distension of the spleen cap­sule. Splenic infarction is manifested by piercing pain which intensifies during breathing. Pain in the bones is not infrequent. It is due to hyperplasia of the myeloid tissue.

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Chapter 9. Diseases of the Blood

Fig. 109. A patient with chronic myeloid leucosis (marked are the borders of the enlarged spleen and liver).

Myeloid infiltration in various internal organs can be the cause of some additional symptoms, such as dyspeptic signs in affections of the gastro­intestinal tract, coughing in the presence of infiltrations in the lungs and the pleura, neurological changes due to affection of the brain, the spinal cord, nerve radices, etc. In the terminal period of the disease, the heart is overloaded due to pronounced anaemization; dyspnoea and oedema develop (their origin being dependent also on hypoproteinaemia). Throm-bocytopenia and shifts in the blood coagulation system cause haemor-rhagic complications. Inspection of the patient helps physician assess his general condition and determine (approximately) the stage of the disease (stage I—the initial symptoms, stage II—pronounced symptoms, and stage III—dystrophy; this is the terminal stage). The terminal stage is characterized by pronounced cachexia and considerable enlargement of the abdomen due to markedly enlarged liver and spleen (Fig. 109). The skin is pallid, with a yellowish or greyish hue; it is flaccid and moist. The legs are affected by oedema. Gingivitis and necrosis of the mouth mucosa are possible. Palpation reveals moderate enlargement of the lymph nodes of various groups. The liver and especially the spleen are markedly enlarged. It is believed that no other disease is attended by enlargement of the spleen to the extent to which it is enlarged in the terminal stage of chronic

myeloleucosis. The liver and the spleen are firm. In the presence of infarc­tions of the spleen it is tender to palpation. Peritoneal friction sound can be heard over the spleen by auscultation. Applying pressure to the bones and tapping over them are painful.

The leucocyte count is markedly high (Plate 33). It can be 3 x 10¹¹ and even 6 x 10¹¹ per 1 1. Leucocyte count can first only slightly exceed the normal level but later it increases, gradually or suddenly. Temporary remissions are possible, especially in the appropriate therapy. In addition to the main form of myeloleucosis characterized by a considerable increase in the white blood cells count (leukaemic), there may be cases with their moderately increased (subleukaemic) and normal counts (aleukaemic). Study of the blood smears reveals mainly cells of granulocytic series which make 95-97 per cent of all white blood elements. There are many im­mature forms among them (myelocytes, promyelocytes, and even myeloblasts). During exacerbation, the number of young forms markedly increases. Only the youngest cells, myeloblasts, and a relatively small number of mature granulocytes (stab and segmented ones) can be revealed in the blood, while the intermediate forms are absent (hiatus leucaemicus). Basophils and eosinophils are usually present in the smear; their percentage can even be increased. Basophilia in 4-5 per cent of cases is regarded as a sign of myeloleucosis. The number of lymphocytes and monocytes decreases to 3—0.5 per cent in grave cases with significant leucocytosis, but their absolute amount in the blood does not change substantially. Red blood changes are only observed at stages II and III of the disease, when anaemia joins the process and progresses. Erythrocyte and haemoglobin content of the blood decreases synchronously. The colour index therefore remains within the normal range (0.8-1.0). Thrombocytopenia develops as the terminal period approaches. ESR usually increases to 30—70 mm/h.

The content of the erythroid precursors markedly decreases in the bone marrow (especially when the disease approaches its terminal stage). Cells of the myeloid series prevail (especially juvenile forms: promyelocytes, myelocytes, and myeloblasts). Megakaryocyte count slightly increases in the first half of the disease. Characteristic also is the increase in the number of basophilic and eosinophilic promyelocytes and myelocytes.

Course. The course of the disease is progressive, sometimes with tran­sient spontaneous remissions. Before modern methods of treatment of the disease were introduced into clinical practice, the average life expectancy of patients was 2.5—3 years (sometimes to 10 years). Today the life of patients is prolonged more significantly. Patients die of cachexia, anaemization in­compatible with life, haemorrhagic complications, or from a joining infec­tion.

Treatment. Myelosan and other cytostatics are prescribed, usually in

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Chapter 9. Diseases of the Blood

combination with 6-mercaptopurine, prednisolone, etc. Patients with a marked splenomegaly are given radiotherapy or dopan. Repeated transfu­sions of blood or packed red cells are indicated in cases with pronounced anaemization.

CHRONIC LYMPHOID LEUCOSIS

Chronic lymphoid leucosis is now regarded as a benign tumour of the immunocompetent tissue. Its haematological basis is mainly B-lymphocytes (morphologically mature but functionally inadequate). Chronic lymphoid leucosis is characterized by systemic hyperplasia of the lymphoid apparatus, lymphoid metaplasia of the spleen, bone marrow, and other organs. Chronic lymphoid leucosis is a common form of leucosis. It usually occurs in the middle-aged and aged individuals (from 35 to 70), mostly in men.

Pathological anatomy. The lymph nodes of various groups are enlarged significantly. Their section is grey or greyish-red. The pattern of the lymph nodes is blurred; microscopy reveals accumulation of lymphoid cells, among which juvenile forms occur. The tonsils are enlarged, their structure is indistinct; microscopy reveals large accumulations of lymphocytes and lymphopoietic cells. The spleen is markedly enlarged but not to the extent to which it is enlarged in chronic myeloleucosis. Its structure is indistinct because of diffuse hyperplasia of the lymphoid tissue. Lymphatic infiltrations are seen in the liver, the stomach wall, pancreas, kidneys, and the skin; in other words, all organs can be affected. Lymphoid metaplasia of the bone marrow is observed.

Clinical picture. The initial symptoms are general weakness, indisposi­tion, and rapid fatigue. The first symptom which troubles the patient and makes him feel like consulting a doctor is usually enlargement of the sub­cutaneous lymph nodes. General weakness gradually increases, excess sweating develops along with subfebrile temperature. Depending on a par­ticular enlarged lymph node group and the organ affected by lymphoid in­filtration, additional symptoms develop: dyspepsia, diarrhoea (in affection of the gastro-intestinal tract), dyspnoea and attacks of asphyxia (in com­pression of the trachea and bronchi by the bifurcation lymph nodes), erythema, dryness and itching of the skin (in leukaemic lymphodermia), etc. Lymphoid metaplasia of the bone marrow may cause haemorrhagic symptoms (due to thrombocytopenia) and anaemia. Leukaemic infiltration can cause radicular pain and exophthalmos. Diffuse lymphatic prolifera­tion in the nasopharynx can develop.

Enlarged lymph nodes can often be revealed during inspection of the patient. Lymph nodes of one or several groups are often enlarged; later all other lymph nodes become also involved. The tonsils can be enlarged too.

Skin infiltration is attended by its consolidation, reddening, dryness and scaling. At the terminal stage, the patients are extremely thin (cachexia).

Palpation is used to assess accurately the enlargement of the lymph nodes and their properties. The lymph nodes are elastic-pasty; they do not fuse with the skin or with one another, and are painless in most cases. They can grow to the size of a hen egg. Even markedly enlarged, the lymph nodes never ulcerate or suppurate (as distinct from tuberculosis affection of the nodes). The liver and the spleen are enlarged and consolidated. In­farctions of the spleen can occur; its palpation then becomes tender.

Leucocyte counts in the leukaemic form of the disease are as high as 3 x 10¹¹ per 11, and more. Lymphocytes make 80—95 per cent of the white blood (Plate 34); they are mostly mature. The structure of their nucleus and cytoplasm is sometimes quite peculiar: the cells are very soft and are easily destroyed when preparing a smear; specific Botkin-Gumprecht shadows are formed. Small amounts of juvenile cells, prolymphocytes and lymphoblasts, occur. During exacerbation their number increases. The relative quantity of neutrophils is much decreased (to 20-4 per cent). The blood picture is less specific in subleukaemic and aleukaemic forms of the disease, where lymphocytosis is usually less pronounced. Anaemia and thrombocytopenia (mainly of the auto-immune genesis) join at the ter­minal period.

Study of the punctate of the bone marrow reveals its lymphoid metaplasia: great quantity of lymphoid cells are found (to 50 and even 90 per cent in especially grave cases). The number of cell elements of the granulocytic and erythroid precursors is decreased. The results of studying the lymph node punctate are less convincing because lymphoid cells are common elements of its parenchyma while the hyperplastic character of the lymphoid tissue is sometimes difficult to determine.

Course. The disease progresses in cycles or gradually. The average life expectancy of patients is 4-5 years. Some survive for 10-12 years and over. The patients die of secondary infections, usually pneumonia (which is promoted by inhibition of humoral immunity), of haemorrhagic complica­tions, and cachexia.

Treatment. Active treatment is not given during the initial period of the disease (like in chronic myeloleucosis). Special attention is given to nor­malization of conditions of work and rest of the patients, who must be fed an adequate diet rich in vitamins and proteins. The patient should walk in the open air. X-ray therapy is given in the presence of toxicosis or if the disease is rapidly progressing. The enlarged lymph nodes and the spleen are irradiated. Leukeran, prednisolone, cyclophosphane and other chemical cytostatics are given. Blood transfusion is indicated in anaemia and throm­bocytopenia.

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Chapter 9. Diseases of the Blood

ERYTHRAEMIA

Erythraemia (chronic erythromyelosis, Vaquez' disease) is a benign myeloproliferative disease characterized by total hyperplasia of the bone marrow cell elements, which is more pronounced in the erythroid precur­sor. Erythraemia was first described by the French clinicist Luis Vaquez in 1892. Aged males are mostly affected.

Erythraemia should be differentiated from erythrocytosis which may be a symptom of some other diseases (chronic diseases of the lungs and the heart, essential hypertension, some kidney diseases, etc.) and erythrocytosis developing in the presence of hypoxia (at high altitudes, e.g. in highland; less frequently in pilots). The symptoms of the main disease prevail in the clinical picture of symptomatic erythrocytosis. During remis­sion, or in cases of recovery, the erythrocyte count in the peripheral blood normalizes. Symptomatic erythrocytosis is not attended by neutrophilic leucocytosis or thrombocytosis, or else splenomegaly, which are common in erythraemia.

Pathological anatomy. Pronounced hyperaemia of the organs and the presence in them of old and new haemorrhages are characteristic. Red bone marrow is affected by hyperplasia; it displaces fat from the diaphysis of the tubular bones. Histological studies reveal increased number of the erythroid series cells. The liver and the spleen are mildly enlarged and plethoric. The left ventricle of the heart is often hypertrophied (in arterial hypertension).

Clinical picture. The onset of the disease is slow and indistinct. When the symptoms are activated, the patient complains of headache, heaviness in the head and noise in the ears, exertional dyspnoea, impaired memory, and skin itching. Vision and hearing function are also impaired in some cases. Pain in the abdomen can develop, probably due to excess blood delivery to the internal organs. Unbearable and burning pain can transient­ly develop in the finger tips (erythromelalgia), which can be explained by transient vascular spasms.

Inspection of the patient reveals peculiar plethoric redness of the expos­ed skin (face, neck, hands). The tongue and the lips are bluish-red, the eye conjunctiva is hyperaemic. This peculiar colour of the skin and mucosa is due to overfilling of the surface vessels with blood and its slow movement in the vessels. The greater part of haemoglobin is thus converted into its reduced form. Palpation reveals moderately enlarged spleen and liver. Tapping over flat bones and exerting pressure on them are painful, which is characteristic of bone marrow hyperplasia.

Arterial pressure (both systolic and diastolic) is often increased. It is believed that arterial hypertension is a compensatory reaction of the vessels to the increased viscosity of blood. In these cases palpation of the apex beat and electrocardiography reveal left-ventricular hypertrophy.... i

The erythrocyte count increases and is usually from 6 x 10¹² to 8 x 10¹² per 1 1, and more; haemoglobin increases to 180-220 g/1; the colour index is less than 1. The total blood circulatory volume increases significantly (1.5—2.5 times) mainly at the expense of increased erythrocyte count. The blood reticulocyte content increases to 15-2O%owhich indicates intensified regeneration of erythrocytes. Polychromasia of erythrocytes is observed; separate erythroblasts can be found in the smear. The number of white blood cells also increases (1.5—2 times) at the expense of neutrophils, whose content is 70-85 per cent. The nuclear shift to the left is observed. The number of eosinophils, less frequently of basophils, increases. The number of thrombocytes increases sharply to 1.5 x 10¹²-2 x 10¹² per 1 1 of blood. ESR is slow, blood viscosity increases significantly, while coagulability of blood and the bleeding time remain normal.

Histological study of the bone marrow (obtained by trepanobiopsy) shows significantly increased number of cells of the erythroid series. The number of juvenile cells of the granulocytic series and of megakaryocytes is also increased.

Course. The disease progresses slowly. The average life expectancy of patients is 10-14 years. The outcome of the disease is myelofibrosis with progressive hypoplastic anaemia or transformation into myeloleucosis. Most frequent complications are thrombosis of the cerebral vessels, spleen, lower extremities, and less frequently of other parts of the body. Tendency to bleeding also develops which is due to both functional inadequacy of thrombocytes and the low relative content of fibrinogen in the blood. Erythraemia patients often develop gastroduodenal ulcer.

Treatment. Radioactive phosphorus (³²P) is the best therapeutic means for erythraemia. It produces a cytostatic effect on haemopoiesis in the bone marrow. Clinical remission, lasting from 1 to 3 years is attained in most cases. New cytostatics (myelosan and marcofan) are also used. Symp­tomatic therapy includes phlebotomy (500 ml) at 5—7 day intervals.

LYMPHOGRANULOMATOSIS, ', ',.

Lymphogranulomatosis is a systemic disease in the group of malignant lymphomas and is characterized by the specific malignant affection of the lymph nodes, the spleen, and other organs. The disease was first described by Thomas Hodgkin in 1832. Hence another name, Hodgkin's disease.

Aetiology and pathogenesis. It is believed that the disease is underlain
by lymphogenic metastasis from the primary focus, which obeys the law of
tumour propagation. Lymphogranulomatosis is possibly a tumour of
histiocytes in which the chromosome set is disordered (Melburn
chromosome). _: ,,...

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Chapter 9. Diseases of the Blood

Pathological anatomy. The main changes are enlargement of various lymph nodes. Their histological studies reveal focal three-stage growths of the granuloma cells. The stage of dif­fuse hyperplasia of the lymph node is followed by focal, and then diffuse proliferation of the reticular and endothelial cells, and also of the cells of juvenile connective tissue. The presence of the Berezovsky-Sternberg cells is especially characteristic. These giant cells have 1, 2 or 3 large nuclei with large nucleoli. Fibrosis develops at the third stage. Necrotic foci are sometimes observed. Lymphogranulomatosis is characterized by a varied histological picture and simultaneous presence of various phases of lymphogranulomatous growths in various lymph nodes. The spleen is enlarged and firm; the section shows many light-grey foci of lym­phogranulomatous proliferations which account for the porphyritic texture. Proliferation of lymphogranulomatous tissue can be seen in other organs, e.g. in the stomach, intestine, liver, etc.

Clinical picture. Weakness and general indisposition are in most cases the first appreciable signs of the disease. Skin itching is among them. It can be excruciating and the patient scratches the skin. The temperature elevates and hidrosis develops. Attacks of fever are first infrequent, but later become more constant. The temperature curve has a specific pattern, to reach 38—39.5 °C at its peaks. The difference between the morning and evening temperatures is 1-2 °C. The main symptom for which the patient would first consult the doctor is gradual swelling of some part of the body, mostly of the neck (due to growth of the lymph nodes). Both surface and deep-seated lymph nodes become enlarged. Considerable enlargement of the lymph nodes of any internal group can involve some additional changes in the patient's condition and cause complaints. For example, when the lymph nodes grow to compress the mediastinum, the trachea or bronchi the patient develops dyspnoea, cough, pain and the pressing sensation in the chest. If the recurrent nerve is compressed, the corresponding vocal cord is affected by paresis and voice becomes hoarse. Lymphogranulomatous af­fection of the stomach causes symptoms of dyspepsia (abdominal pain, regurgitation, vomiting, etc.). If the abdominal lymph nodes and the in­testine are involved, persistent constipation may develop.

Findings of physical examination show enlargement of the lymph nodes which is the most characteristic sign of the disease. The cervical lymph nodes (mostly on the right side of the neck) become enlarged in more than 50 per cent cases; the nodes of the other side of the neck become involved later. Next involved are submandibular, supra- and subclavicular, axillary, femoral, and inguinal lymph nodes; less frequently the lymph nodes of the other regions (occipital, ulnar, etc.) are involved.

Newly involved nodes are soft, while the old ones become very firm. They fuse together to form conglomerates but do not adhere to the skin. The nodes are painless, they do not suppurate or open, as distinct from actinomycosis- or tuberculosis-affected nodes (scrofuloderma). If a group of lymph nodes is enlarged considerably, the overlying skin becomes dark-

red and then bronze due to disordered circulation; it does not however get thin.

Inspection of the patient reveals some symptoms caused by compres­sion of the vessels and nervous trunks by the enlarged lymph nodes (regional cyanosis, dilatation of the veins, Homer's symptom, etc.). Ab­dominal lymph nodes can be palpated if their enlargement is considerable. A tuberous tumour can be felt in the mesogastric region round the um­bilicus. The spleen is enlarged and firm; it is tender in the presence of perisplenitis. Enlargement of the liver is less characteristic. Enlargement of the mediastinal lymph nodes can best of all be revealed by X-rays.

Hypochromic anaemia and neutrophilic leucocytosis are usually found; lymphocyte counts (absolute and relative quantities) are low. Eosinophilia and thrombocytopenia may also occur. ESR is increased: at the terminal stage it is 50—70 mm/h. Study of the punctate of the bone marrow is not quite informative but the Berezovsky-Sternberg cells may often be observ­ed.

Histological study of lymph node bioptates (Plate 35) reliably confirms the diagnosis of lymphogranulomatosis. The cell composition of the lym­phogranulomatous tissue is as a rule quite varied but its most specific ele­ment are granulomas with giant cells to 30—80 ^m in diameter (Berezovsky-Sternberg polynuclear cells which do not occur in other diseases). Study of the content of lymph nodes is more accessible but less informative.