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Cutaneous Manifestations of Lymphoma Including Leukemia
Cutaneous Manifestations of Lymphoma Including Leukelnia ROBERT R. KIERLAND
No STANDARD classification has been devised for the many and varied cutaneous manifestations of the lymphoblastomas, or as they are often called, "the lymphomas." Those to be discussed in this paper include mycosis fungoides, Hodgkin's disease, lymphosarcoma and leukemia cutis. Certain less common allied conditions which cannot be considered in the scope of this paper have been well presented by Montgomery. All of the diseases under consideration appear to be closely related diseases and even the cutaneous manifestations may be similar. For example, a patient may have clinical evidence on the skin of mycosis fungoides, yet examination of a smear of the peripheral blood may indicate leukemia and the pathologic appearance of an excised lymph node may suggest lymphosarcoma. It has been estimated that 25 to 40 per cent of patients with lymphoblastoma will exhibit cutaneous signs and symptoms during the course of their disease. These manifestations may be specific or nonspecific in the sense that the microscopic examination of excised tissue will or will not show diagnostic features of lymphoma or leukemia. It is further true that the microscopic findings may be diagnostic for lymphoblastoma but not diagnostic for the type of lymphoblastoma present. NONSPECIFIC CUTANEOUS MANIFESTATIONS
The nonspecific cutaneous manifestations of the lymphomas including leukemia are many and varied. Practically everything from pruritus without cutaneous signs to universal erythroderma and exfoliative dermatitis may be presented. Generalized severe pruritus may be the presenting symptom of Hodgkin's disease or lymphosarcoma and may be the one cutaneous symptom suggesting a correct clinical diagnosis. In any patient complaining of generalized pruritus without any explanatory cutaneous change, lymphoblastoma must be one of the first conditions to be excluded. Pruritus also usually accompanies the other specific and nonspecific cutaneous findings of leukemia and the other lymphomas. 114-1
1142
Robert R. Kierland
Purpura in the form of petechiae, ecchymoses, deep subcutaneous contusions, easy bruising and ready bleeding from mucous membranes is another nonspecific cutaneous manifestation of this group of diseases, especially of leukemia. The individual purpuric lesion or groups of lesions in themselves are not diagnostic but are highly suggestive of leukemia. Other conditions, among them allergic purpuras, purpura simplex and drug eruptions, produce purpura also and must be considered in the differential diagnosis. Urticaria and signs of erythema multiforme are further nonspecific signs that may occur in any stage of lymphoma. The individual lesions are transient but recur frequently. The exact mechanism involved in their production is unknown but is considered by many to be a toxic process. These findings together with generalized pruritus occasionally are used to measure response to treatment. Marked improvement or disappearance of these signs may indicate beneficial response or control while recurrence suggests that the condition is active again. In this connection it should be remembered that erythema multiforme may be a sequel of roentgen therapy, and also that all these cutaneous manifestations may be produced by the chemotherapy of lymphoma. Universal erythroderma and exfoliative dermatitis may make its appearance early or late in the course of leukemia or the other lymphomas, and may be specific or nonspecific. It has been said that in as many as 50 per cent of all cases, in which exfoliative dermatitis occurs in the later decades of life, the disease may be of lymphoblastomatous origin. Eczematous eruptions leading to exfoliative dermatitis also may be seen as a consequence of ill-advised treatment of other specific and nonspecific cutaneous signs or symptoms. Although the manifestations just mentioned comprise the majority of the nonspecific cutaneous manifestations, others are seen occasionally. These are localized or generalized bullous eruptions suggesting dermatitis herpetiformis or pemphigus; eczematous or psoriasiform plaques; hyperpigmentations usually in connection with cutaneous manifestations of long duration; herpes zoster from lymphoblastomatous infiltration about a dorsal nerve root, and lymphedema from infiltration of lymph channels and nodes. SPECIFIC CUTANEOUS CHANGES
The specific cutaneous changes of the lymphomas including leukemia also vary in form and degree but frequently a clinical diagnosis may be made and confirmed by microscopic examinations later. This is true particularly for mycosis fungoides which is primarily a cutaneous disease. The details of specific manifestations will be dealt with in detail later when specific entities are considered. In a broad sense the specific manifestations are usually discrete or confluent infiltrated plaques, nodules or tumors some of which may have undergone necrosis leading to ulceration.
Cutaneous M anijestations oj Lymphoma
1143
In patients with nonspecific clinical findings of hemorrhage, psoriasiform plaques or exfoliative dermatitis, microscopic examination of excised skin may reveal findings specifically diagnostic of leukemia or one of the other lymphomas. In this connection it is important that the site for biopsy be selected carefully and if possible that it be an infiltrated area. At this point some mention should be made of lipomelanic reticulosis which is a pathologic diagnosis of the findings in certain lymph nodes. It has been thought by some that this is a diagnostic feature of the lymphomas. My colleagues and I do not subscribe to this, for we have seen many patients with chronic inflammatory dermatoses due to various causes whose lymph nodes showed lipomelanic reticulosis. In other words, lipomelanic reticulosis i3 a secondary phenomenon and it is secondary to chronic inflammatory dermatosis of any cause. MYCOSIS FUNGOIDES
Mycosis fungoides is primarily a skin disease which occasionally involves internal organs and which may eventuate terminally in any of the other conditions under consideration. 1 The classic clinical appearance is a generalized cutaneous eruption composed of discrete and confluent noninfiltrated and infiltrated scaly erythematous plaques, nodules and tumors which may arise in the plaques or independently, and in any given area there are lesions of different ages and evolution even to the point of spontaneous healing (Fig. 146). At the onset, however, there may be localized or generalized pruritus with a few scattered, ill-defined,
Fig. 146. Mycosis fungoides. Note tumors and infiltrated plaques.
114-4-
Robert R. Kierland
dry, scaly and slightly red plaques. The following phases of mycosis fungoides have been recognized: (1) premycotic or noninfiltrated, (2) infiltrated, (3) tumorous, (4) erythrodermic and (5) the phase of mycosis fungoides d'emblee. The premycotic or noninfiltrated phase of mycosis fungoides suggests parapsoriasis en plaque or even the plaque type of asteatotic dermatitis. Some dermatologists have thought that parapsoriasis en plaque may eventuate in mycosis fungoides; however, most dermatologists now are of the opinion that the premycotic phase of mycosis fungoides is really mycosis fungoides from the onset of the eruption. The faint ill-defined plaques and scaly red plaques may persist as such for months or years and frequently improve or disappear during the warm summer months. Later the disease enters the infiltrative phase. Not all plaques become infiltrated however; some remain as parapsoriasiform or eczematous lesions, some become more intensely red and scaly, and others become slightly or thickly infiltrated. In this phase the eruption first becomes recognizable clinically. Still later the tumor phase becomes apparent. The nodules and tumors may arise from apparently normal skin or the infiltrated plaques. Certain of the tumors enlarge slowly, others rapidly, while some ulcerate because of pressure from the underlying dense infiltrate. The erythrodermic phase may be the original phase or the terminal stage. In any event the appearance is not unlike that of poikiloderma: there is a generalized diffuse erythematous scaly eruption with scattered blotchy telangiectatic lesions, areas of hyperpigmentation and suggestions of cutaneous mild atrophy. In this phase, the infiltrated plaques, nodules or tumors may appear also. The d'emblee type of mycosis fungoides starts from the onset with nodules and tumors without going through the preliminary phases just mentioned. The disease usually runs a more rapid and fulminating course, and death occurs relatively early. No one can prognosticate accurately the course of mycosis fungoides. At the Clinic we have under observation a man whose eruption was first diagnosed as mycosis fungoides in 1917; other patients have died of their disease in a few months. The response to treatment (usually roentgen therapy) is at first satisfactory but later the eruption becomes resistant to any form of therapy. The clinical diagnosis of mycosis fungoides is confirmed by the microscopic and histopathologic appearance of tissue removed at biopsy. Imprint or touch smears have diagnostic value here but are of greater value in the diagnosis of cutaneous leukemia. HODGKIN'S DISEASE AND LYMPHOSARCOMA
The specific cutaneous manifestations4 of Hodgkin's disease and lymphosarcoma are uncommon while the nonspecific changes are seen fre-
Cutaneous M anijestations oj Lymphoma
1145
quently. The specific findings are usually grouped nodules which form plaques in which ulceration may appear or there may be solitary scattered large tumors with or without ulceration (Fig. 147); rarely the onset may be an exfoliative erythroderma (Fig. 148). These lesions are not specific in the clinical sense but are specific pathologically. Nonspecific manifestations of Hodgkin's disease and lymphosarcoma are seen most frequently in the form of intense severe pruritus with consequent excoriations. These excoriations are frequently long, linear and parallel, not unlike those seen in vagabond's disease (pediculosis cor-
Fig. 147. Hodgkin's disease showing discrete tumors with ulceration.
poris). Secondary infection of the excoriations and skin with eczematization frequently supervenes. Later hyperpigmentation may appear. Herpes zoster is not uncommon. The other nonspecific manifestations mentioned earlier also may be present but less frequently. While most instances of cutaneous Hodgkin's disease have their origin from an underlying focus, the disease may begin primarily in the skin (autochthonous). THE LEUKEMIAS
Leukemia cutis may be divided into the lymphatic (Fig. 149) myelogenous and monocytic types; the last includes reticuloendotheliosis (Fig. 150).6 The majority of specific cutaneous changes arise by extension from underlying foci or are metastatic; nevertheless, leukemia as with the
1146
Robert R. K ierland
other lymphomas under discussion may originate in the skin and the pattern of cutaneous lesions is not unlike that of the other lymphomas. The specific lesions may present themselves in a multiplicity of types. Innumerable small discrete erythematous nodules may constitute the entire eruption. 3 There may be few but large plum-colored tumors which sometimes undergo ulceration, or the manifestation may be an intensely pruritic exfoliative dermatitis with or without poikilodermatous changes.
Fig. 148. Hodgkin's disease showing erythroderma and evidences of intense pruritus.
Bullous specific eruptions, especially those in the light exposed areas, may be uncommon. 2 Except as a temporary beneficial response to'.treatment the specific eruptions tend to progress; the individual nodules become larger and fuse with one another, ulceration appears as a result of pressure of the dense underlying infiltrate, and specific infiltrations and hemorrhage appear in areas of exfoliative dermatitis. Hemorrhagic areas while not clinically diagnostic of leukemia may reveal specific findings when a specimen removed at biopsy is examined microscopically. Hemorrhage without the cutaneous lesions or hemorrhage into bullae, nodules
Cutaneous Manifestations of Lymphoma
11//,
Fig. 149. Lymphatic leukemia showing infiltrated leukemic plaques.
Fig. 150. Leukemic reticuloendotheliosis. Note innumerable, discrete, small nodules.
Robert R. Kierland
1148
and tumors or areas of dermatitis is seen more frequently in leukemia cutis than in the other lymphomas. As in the other lymphomas, pruritus of generalized nature is frequently a nonspecific manifestation of leukemia cutis. Urticaria of recurrent type may appear early or late and frequently appears as small urticarial papules. Petechiae and ecchymoses, of course, appear frequently but by themselves are not diagnostic clinically. Lesions resembling erythema multiforme and those resembling prurigo may be present also. The nonspecific cutaneous manifestations of leukemia are termed by many as "leukamids" or "leukemids." COURSE OF LYMPHOMAS
A fatal termination is an almost invariable rule in the types of lymphoma considered, yet the rapidity with which this develops varies greatly from patient to patient. The entire course may be a matter of days or weeks in acute leukemia or many years especially in mycosis fungoides. The duration of disease cannot be predicted accurately except in the occasional patient. Usually when the lymphoma originates in the skin, the interval from onset to death is longer than when the cutaneous lesions are metastatic or arise by extension from deeper involvement. In any type of lymphoma, severe, acutely progressive and fulminating, nonspecific and specific lesions or hemorrhage often indicates an early death. PATHOLOGY AND TREATMENT
Except to emphasize a few salient features, details of pathology and treatment cannot be covered in the space allotted this paper. There is no clear-cut distinction between anyone of the entities which comprise the group of lymphomas; one type may merge into another while microscopic examinations of different tissues in one patient may suggest the different entities of lymphoma. Nevertheless, the confirmation of the diagnosis of cutaneous lymphoma must always be made histologically. Wilson, Winer and others have emphasized the importance of touch or imprint smears done at the time of biopsy as a most valuable aid in proper diagnosis. This technique should be employed with greater frequency than it is now. Treatment for the majority of patients with lymphoma is satisfactory to the point of producing temporary relief of subjective symptoms and objective signs. Sooner or later, however, the cutaneous lesions recur after treatment with greater rapidity and in greater profusion. Roentgen therapy is the most frequently employed method of treatment yet many adjuncts exist which may be used in combination with roentgen therapy or which may be administered when the response to irradiation is no longer efficacious. These consist of steroids (cortisone or its derivatives), the mustards, folic acid antagonists, antimony, salts of para-aminobenzoic acid, urethane, and other chemotherapeutic agents. Occasionally
Cutaneous Manifestations of Lymphoma
1149
the surgical excision of the autochthonous lesion of lymphosarcoma, and other isolated cutaneous forms of lymphoma has resulted in apparent cure. Pruritus and urticaria may be treated symptomatically with the usual antipruritic and urticarial remedies but beneficial results are of short duration and generally poor. None of these therapeutic modalities can be used with impunity and those wishing to administer them must be trained and experienced in their use. SUMMARY
In this short account of the cutaneous manifestations of the lymphomas including leukemia emphasis has been given to the clinical, specific and nonspecific cutaneous signs and symptoms. The entities comprising this group of diseases frequently are not clear cut but may merge clinically and pathologically. The clinical diagnosis or suspicion of lymphoma must be confirmed histopathologically, and the touch or imprint smear is a valuable technique in diagnosis. Those who supervise treatment must be trained and experienced in the therapeutic modalities employed. REFERENCES 1. Bluefarb, S. M.: Is Mycosis Fungoides an Entity? A.M.A. Arch. Dermat. 71:293302 (March) 1955. 2. Costello, M. J., Canizares, Orlando, Montague, Meredith III and Buncke, C. M.: Cutaneous Manifestations of Myelogenous Leukemia. A.M.A. Arch. Dermat. 71 :605-614 (March) 1955. 3. Feldaker, Mauri, Kierland, R. R. and Montgomery, Hamilton: Cutaneous Lymphoblastoma: Report of Two Unusual Cases of Reticulum Cell Sarcoma with Emphasis on Cutaneous Touch Smears. A.M.A. Arch. Dermat. & Syph. 70:583-589 (Nov.) 1954. 4. Kierland, R. R. and Montgomery, Hamilton: Cutaneous Ulcerative Hodgkin's Disease. Proc. Staff Meet., Mayo Clin. 16:124-128 (Feb. 19) 1941. 5. Montgomery, Hamilton: Mycosis Fungoides, Lymphoblastoma of Skin and Allied Conditions as General Diseases. In Christian, H. A.: Oxford Medicine. New York, Oxford University Press, 1950, Vo!. 4, Pt. 1, pp. 44, (1)-44 (20-23). 6. Wilson, G. T.: Cutaneous Smears: A Diagnostic Aid in Certain Malignant Lesions of Skin. J. Invest. Dermat. 22:173-187 (March) 1954. 7. Winer, L. H.: Mycosis Fungoides: Benign and Malignant Reticulum Cell Dysplasia. Arch. Dermat. & Syph. 56:480-498 (Oct.) 1947.
No STANDARD classification has been devised for the many and varied cutaneous manifestations of the lymphoblastomas, or as they are often called, "the lymphomas." Those to be discussed in this paper include mycosis fungoides, Hodgkin's disease, lymphosarcoma and leukemia cutis. Certain less common allied conditions which cannot be considered in the scope of this paper have been well presented by Montgomery. All of the diseases under consideration appear to be closely related diseases and even the cutaneous manifestations may be similar. For example, a patient may have clinical evidence on the skin of mycosis fungoides, yet examination of a smear of the peripheral blood may indicate leukemia and the pathologic appearance of an excised lymph node may suggest lymphosarcoma. It has been estimated that 25 to 40 per cent of patients with lymphoblastoma will exhibit cutaneous signs and symptoms during the course of their disease. These manifestations may be specific or nonspecific in the sense that the microscopic examination of excised tissue will or will not show diagnostic features of lymphoma or leukemia. It is further true that the microscopic findings may be diagnostic for lymphoblastoma but not diagnostic for the type of lymphoblastoma present. NONSPECIFIC CUTANEOUS MANIFESTATIONS
The nonspecific cutaneous manifestations of the lymphomas including leukemia are many and varied. Practically everything from pruritus without cutaneous signs to universal erythroderma and exfoliative dermatitis may be presented. Generalized severe pruritus may be the presenting symptom of Hodgkin's disease or lymphosarcoma and may be the one cutaneous symptom suggesting a correct clinical diagnosis. In any patient complaining of generalized pruritus without any explanatory cutaneous change, lymphoblastoma must be one of the first conditions to be excluded. Pruritus also usually accompanies the other specific and nonspecific cutaneous findings of leukemia and the other lymphomas. 114-1
1142
Robert R. Kierland
Purpura in the form of petechiae, ecchymoses, deep subcutaneous contusions, easy bruising and ready bleeding from mucous membranes is another nonspecific cutaneous manifestation of this group of diseases, especially of leukemia. The individual purpuric lesion or groups of lesions in themselves are not diagnostic but are highly suggestive of leukemia. Other conditions, among them allergic purpuras, purpura simplex and drug eruptions, produce purpura also and must be considered in the differential diagnosis. Urticaria and signs of erythema multiforme are further nonspecific signs that may occur in any stage of lymphoma. The individual lesions are transient but recur frequently. The exact mechanism involved in their production is unknown but is considered by many to be a toxic process. These findings together with generalized pruritus occasionally are used to measure response to treatment. Marked improvement or disappearance of these signs may indicate beneficial response or control while recurrence suggests that the condition is active again. In this connection it should be remembered that erythema multiforme may be a sequel of roentgen therapy, and also that all these cutaneous manifestations may be produced by the chemotherapy of lymphoma. Universal erythroderma and exfoliative dermatitis may make its appearance early or late in the course of leukemia or the other lymphomas, and may be specific or nonspecific. It has been said that in as many as 50 per cent of all cases, in which exfoliative dermatitis occurs in the later decades of life, the disease may be of lymphoblastomatous origin. Eczematous eruptions leading to exfoliative dermatitis also may be seen as a consequence of ill-advised treatment of other specific and nonspecific cutaneous signs or symptoms. Although the manifestations just mentioned comprise the majority of the nonspecific cutaneous manifestations, others are seen occasionally. These are localized or generalized bullous eruptions suggesting dermatitis herpetiformis or pemphigus; eczematous or psoriasiform plaques; hyperpigmentations usually in connection with cutaneous manifestations of long duration; herpes zoster from lymphoblastomatous infiltration about a dorsal nerve root, and lymphedema from infiltration of lymph channels and nodes. SPECIFIC CUTANEOUS CHANGES
The specific cutaneous changes of the lymphomas including leukemia also vary in form and degree but frequently a clinical diagnosis may be made and confirmed by microscopic examinations later. This is true particularly for mycosis fungoides which is primarily a cutaneous disease. The details of specific manifestations will be dealt with in detail later when specific entities are considered. In a broad sense the specific manifestations are usually discrete or confluent infiltrated plaques, nodules or tumors some of which may have undergone necrosis leading to ulceration.
Cutaneous M anijestations oj Lymphoma
1143
In patients with nonspecific clinical findings of hemorrhage, psoriasiform plaques or exfoliative dermatitis, microscopic examination of excised skin may reveal findings specifically diagnostic of leukemia or one of the other lymphomas. In this connection it is important that the site for biopsy be selected carefully and if possible that it be an infiltrated area. At this point some mention should be made of lipomelanic reticulosis which is a pathologic diagnosis of the findings in certain lymph nodes. It has been thought by some that this is a diagnostic feature of the lymphomas. My colleagues and I do not subscribe to this, for we have seen many patients with chronic inflammatory dermatoses due to various causes whose lymph nodes showed lipomelanic reticulosis. In other words, lipomelanic reticulosis i3 a secondary phenomenon and it is secondary to chronic inflammatory dermatosis of any cause. MYCOSIS FUNGOIDES
Mycosis fungoides is primarily a skin disease which occasionally involves internal organs and which may eventuate terminally in any of the other conditions under consideration. 1 The classic clinical appearance is a generalized cutaneous eruption composed of discrete and confluent noninfiltrated and infiltrated scaly erythematous plaques, nodules and tumors which may arise in the plaques or independently, and in any given area there are lesions of different ages and evolution even to the point of spontaneous healing (Fig. 146). At the onset, however, there may be localized or generalized pruritus with a few scattered, ill-defined,
Fig. 146. Mycosis fungoides. Note tumors and infiltrated plaques.
114-4-
Robert R. Kierland
dry, scaly and slightly red plaques. The following phases of mycosis fungoides have been recognized: (1) premycotic or noninfiltrated, (2) infiltrated, (3) tumorous, (4) erythrodermic and (5) the phase of mycosis fungoides d'emblee. The premycotic or noninfiltrated phase of mycosis fungoides suggests parapsoriasis en plaque or even the plaque type of asteatotic dermatitis. Some dermatologists have thought that parapsoriasis en plaque may eventuate in mycosis fungoides; however, most dermatologists now are of the opinion that the premycotic phase of mycosis fungoides is really mycosis fungoides from the onset of the eruption. The faint ill-defined plaques and scaly red plaques may persist as such for months or years and frequently improve or disappear during the warm summer months. Later the disease enters the infiltrative phase. Not all plaques become infiltrated however; some remain as parapsoriasiform or eczematous lesions, some become more intensely red and scaly, and others become slightly or thickly infiltrated. In this phase the eruption first becomes recognizable clinically. Still later the tumor phase becomes apparent. The nodules and tumors may arise from apparently normal skin or the infiltrated plaques. Certain of the tumors enlarge slowly, others rapidly, while some ulcerate because of pressure from the underlying dense infiltrate. The erythrodermic phase may be the original phase or the terminal stage. In any event the appearance is not unlike that of poikiloderma: there is a generalized diffuse erythematous scaly eruption with scattered blotchy telangiectatic lesions, areas of hyperpigmentation and suggestions of cutaneous mild atrophy. In this phase, the infiltrated plaques, nodules or tumors may appear also. The d'emblee type of mycosis fungoides starts from the onset with nodules and tumors without going through the preliminary phases just mentioned. The disease usually runs a more rapid and fulminating course, and death occurs relatively early. No one can prognosticate accurately the course of mycosis fungoides. At the Clinic we have under observation a man whose eruption was first diagnosed as mycosis fungoides in 1917; other patients have died of their disease in a few months. The response to treatment (usually roentgen therapy) is at first satisfactory but later the eruption becomes resistant to any form of therapy. The clinical diagnosis of mycosis fungoides is confirmed by the microscopic and histopathologic appearance of tissue removed at biopsy. Imprint or touch smears have diagnostic value here but are of greater value in the diagnosis of cutaneous leukemia. HODGKIN'S DISEASE AND LYMPHOSARCOMA
The specific cutaneous manifestations4 of Hodgkin's disease and lymphosarcoma are uncommon while the nonspecific changes are seen fre-
Cutaneous M anijestations oj Lymphoma
1145
quently. The specific findings are usually grouped nodules which form plaques in which ulceration may appear or there may be solitary scattered large tumors with or without ulceration (Fig. 147); rarely the onset may be an exfoliative erythroderma (Fig. 148). These lesions are not specific in the clinical sense but are specific pathologically. Nonspecific manifestations of Hodgkin's disease and lymphosarcoma are seen most frequently in the form of intense severe pruritus with consequent excoriations. These excoriations are frequently long, linear and parallel, not unlike those seen in vagabond's disease (pediculosis cor-
Fig. 147. Hodgkin's disease showing discrete tumors with ulceration.
poris). Secondary infection of the excoriations and skin with eczematization frequently supervenes. Later hyperpigmentation may appear. Herpes zoster is not uncommon. The other nonspecific manifestations mentioned earlier also may be present but less frequently. While most instances of cutaneous Hodgkin's disease have their origin from an underlying focus, the disease may begin primarily in the skin (autochthonous). THE LEUKEMIAS
Leukemia cutis may be divided into the lymphatic (Fig. 149) myelogenous and monocytic types; the last includes reticuloendotheliosis (Fig. 150).6 The majority of specific cutaneous changes arise by extension from underlying foci or are metastatic; nevertheless, leukemia as with the
1146
Robert R. K ierland
other lymphomas under discussion may originate in the skin and the pattern of cutaneous lesions is not unlike that of the other lymphomas. The specific lesions may present themselves in a multiplicity of types. Innumerable small discrete erythematous nodules may constitute the entire eruption. 3 There may be few but large plum-colored tumors which sometimes undergo ulceration, or the manifestation may be an intensely pruritic exfoliative dermatitis with or without poikilodermatous changes.
Fig. 148. Hodgkin's disease showing erythroderma and evidences of intense pruritus.
Bullous specific eruptions, especially those in the light exposed areas, may be uncommon. 2 Except as a temporary beneficial response to'.treatment the specific eruptions tend to progress; the individual nodules become larger and fuse with one another, ulceration appears as a result of pressure of the dense underlying infiltrate, and specific infiltrations and hemorrhage appear in areas of exfoliative dermatitis. Hemorrhagic areas while not clinically diagnostic of leukemia may reveal specific findings when a specimen removed at biopsy is examined microscopically. Hemorrhage without the cutaneous lesions or hemorrhage into bullae, nodules
Cutaneous Manifestations of Lymphoma
11//,
Fig. 149. Lymphatic leukemia showing infiltrated leukemic plaques.
Fig. 150. Leukemic reticuloendotheliosis. Note innumerable, discrete, small nodules.
Robert R. Kierland
1148
and tumors or areas of dermatitis is seen more frequently in leukemia cutis than in the other lymphomas. As in the other lymphomas, pruritus of generalized nature is frequently a nonspecific manifestation of leukemia cutis. Urticaria of recurrent type may appear early or late and frequently appears as small urticarial papules. Petechiae and ecchymoses, of course, appear frequently but by themselves are not diagnostic clinically. Lesions resembling erythema multiforme and those resembling prurigo may be present also. The nonspecific cutaneous manifestations of leukemia are termed by many as "leukamids" or "leukemids." COURSE OF LYMPHOMAS
A fatal termination is an almost invariable rule in the types of lymphoma considered, yet the rapidity with which this develops varies greatly from patient to patient. The entire course may be a matter of days or weeks in acute leukemia or many years especially in mycosis fungoides. The duration of disease cannot be predicted accurately except in the occasional patient. Usually when the lymphoma originates in the skin, the interval from onset to death is longer than when the cutaneous lesions are metastatic or arise by extension from deeper involvement. In any type of lymphoma, severe, acutely progressive and fulminating, nonspecific and specific lesions or hemorrhage often indicates an early death. PATHOLOGY AND TREATMENT
Except to emphasize a few salient features, details of pathology and treatment cannot be covered in the space allotted this paper. There is no clear-cut distinction between anyone of the entities which comprise the group of lymphomas; one type may merge into another while microscopic examinations of different tissues in one patient may suggest the different entities of lymphoma. Nevertheless, the confirmation of the diagnosis of cutaneous lymphoma must always be made histologically. Wilson, Winer and others have emphasized the importance of touch or imprint smears done at the time of biopsy as a most valuable aid in proper diagnosis. This technique should be employed with greater frequency than it is now. Treatment for the majority of patients with lymphoma is satisfactory to the point of producing temporary relief of subjective symptoms and objective signs. Sooner or later, however, the cutaneous lesions recur after treatment with greater rapidity and in greater profusion. Roentgen therapy is the most frequently employed method of treatment yet many adjuncts exist which may be used in combination with roentgen therapy or which may be administered when the response to irradiation is no longer efficacious. These consist of steroids (cortisone or its derivatives), the mustards, folic acid antagonists, antimony, salts of para-aminobenzoic acid, urethane, and other chemotherapeutic agents. Occasionally
Cutaneous Manifestations of Lymphoma
1149
the surgical excision of the autochthonous lesion of lymphosarcoma, and other isolated cutaneous forms of lymphoma has resulted in apparent cure. Pruritus and urticaria may be treated symptomatically with the usual antipruritic and urticarial remedies but beneficial results are of short duration and generally poor. None of these therapeutic modalities can be used with impunity and those wishing to administer them must be trained and experienced in their use. SUMMARY
In this short account of the cutaneous manifestations of the lymphomas including leukemia emphasis has been given to the clinical, specific and nonspecific cutaneous signs and symptoms. The entities comprising this group of diseases frequently are not clear cut but may merge clinically and pathologically. The clinical diagnosis or suspicion of lymphoma must be confirmed histopathologically, and the touch or imprint smear is a valuable technique in diagnosis. Those who supervise treatment must be trained and experienced in the therapeutic modalities employed. REFERENCES 1. Bluefarb, S. M.: Is Mycosis Fungoides an Entity? A.M.A. Arch. Dermat. 71:293302 (March) 1955. 2. Costello, M. J., Canizares, Orlando, Montague, Meredith III and Buncke, C. M.: Cutaneous Manifestations of Myelogenous Leukemia. A.M.A. Arch. Dermat. 71 :605-614 (March) 1955. 3. Feldaker, Mauri, Kierland, R. R. and Montgomery, Hamilton: Cutaneous Lymphoblastoma: Report of Two Unusual Cases of Reticulum Cell Sarcoma with Emphasis on Cutaneous Touch Smears. A.M.A. Arch. Dermat. & Syph. 70:583-589 (Nov.) 1954. 4. Kierland, R. R. and Montgomery, Hamilton: Cutaneous Ulcerative Hodgkin's Disease. Proc. Staff Meet., Mayo Clin. 16:124-128 (Feb. 19) 1941. 5. Montgomery, Hamilton: Mycosis Fungoides, Lymphoblastoma of Skin and Allied Conditions as General Diseases. In Christian, H. A.: Oxford Medicine. New York, Oxford University Press, 1950, Vo!. 4, Pt. 1, pp. 44, (1)-44 (20-23). 6. Wilson, G. T.: Cutaneous Smears: A Diagnostic Aid in Certain Malignant Lesions of Skin. J. Invest. Dermat. 22:173-187 (March) 1954. 7. Winer, L. H.: Mycosis Fungoides: Benign and Malignant Reticulum Cell Dysplasia. Arch. Dermat. & Syph. 56:480-498 (Oct.) 1947.