Henry Ford Hospital Medical Journal

Volume 18 | Number 4 Article 4

12-1970 Mycosis Fungoides with Thrombotic Microangiopathy and Major Central Nervous System Manifestations T. A. Chapel

S. M. Saeed

B. W. Steinhauer

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Recommended Citation Chapel, T. A.; Saeed, S. M.; and Steinhauer, B. W. (1970) "Mycosis Fungoides with Thrombotic Microangiopathy and Major Central Nervous System Manifestations," Henry Ford Hospital Medical Journal : Vol. 18 : No. 4 , 237-244. Available at: https://scholarlycommons.henryford.com/hfhmedjournal/vol18/iss4/4

This Article is brought to you for free and open access by Henry Ford Health System Scholarly Commons. It has been accepted for inclusion in Henry Ford Hospital Medical Journal by an authorized editor of Henry Ford Health System Scholarly Commons. Henry Ford Hosp. Med. Journal Vol. 18, No. 4, 1970

Mycosis Fungoides with Thrombotic Microangiopathy and Major Central Nervous System Manifestations

T. A. Chapel, M.D.;* S. M. Saeed, M.B.B.S.,** and B.W. Steinhauer, M.D.***

A case of mycosis fungoides is presented which terminated in death by an acute central nervous system illness. Autopsy revealed thrombotic microangiopathy. This is felt to be the first report of thrombotic thrombocytopenic purpura occurring in a patient with mycosis fungoides. Since thrombotic thrombocytopenic purpura has been reported in association with other malignancies, the association of these relatively rare disorders may represent more than a coincidence.

Mycosis fungoides (MF) is a malig­ Case Report nant reticulosis arising within the skin. This 58-year-old, Negro female was Its position in the lymphomatous dis­ first seen in the Henry Ford Hospital orders is controversial, although many Dermatology Clinic in January of 1968 when she presented with a generalized authors accept it as a distinct disease eruption. She gave the history of having entity on clinical and histological developed hives after eating tomatoes. A grounds. Visceral involvement is com­ provisional diagnosis of skin allergy was made with the possibility of mycosis fun­ mon and can be the immediate cause goides. There was no follow-up because she of death. left for Tennessee. A variety of central nervous system The patient was next seen in the Emer­ gency Room of the Hospital on August 6, effects of mycosis fungoides have been 1968, with epigastric pain, nausea, vomiting, reported and will be reviewed here. The bilateral supraorbital headaches, and leth­ present case of mycosis fungoides was argy. There had been a 10-pound weight loss over a two-month period. She had a terminated by an acute central nervous previous history of hypertension. system illness found, at autopsy, to be On physical examination, the patient a thrombotic microangiopathy. Al­ was in moderate distress and had a gen­ though the latter disorder has been eralized pruritic eruption. There were num­ erous areas of hypopigmentation with -other found in association with other malig­ areas of hyperpigmentation; numerous nancies, the present combination of plaques and papules showed changes of diseases to our knowledge has never lichenification and several showed excoria­ tion. All of the lesions, which covered the been previously published. entire body including the palms and soles of the feet, were covered by a fine scale. The remainder of the physical examination "'Department of Dermatology was unremarkable except for minimal ar­ * "'Department of Pathology teriovenous compression seen in the fundus, "'* "'Third Medical Division, Department a grade II/VI systolic ejection murmur at of Medicine the right apex, and blood pressure of 210/

237 Chapel, Saeed and Steinhauer

110. There were no abdominal masses. creased cellularity with a ME ratio of 2.5: Neurologic examination was negative ex­ 1.0. Normoblasts and megakaryocytes were cept for lethargy. increased. No tumor cells or granulomata were found. Following admission, an exci- Laboratory Data sional biopsy performed on one of the Hemoglobin was 8 grams per cent, white skin lesions of the left forearm disclosed the count 22,200 with a distribution of 70% plaque stage of mycosis fungoides (Fig 1). polymorphs, 23% lymphocytes and 3 atypi­ cal lymphs; platelet count was 26,900 Hospital Course cu mm. Tests of liver function were nor­ The patient underwent a stormy febrile mal. BUN was 32, blood sugar 66 mg %, course, with increasingly impaired cere­ VDRL was nonreactive and urine porpho­ bration. Skull x-rays and echograms of bilinogen negative. Urine: specific gravity the skull were normal except for the possi­ 1.006, 4 plus albumin, numerous white cells ble postglenoid thinning. The brain scan was with a few coarse granular casts and 4 to class III with increased activity on the 5 red blood cells per high powered field. right anterior side. For this reason a right Blood cultures taken during this patient's carotid arteriogram was carried out and was febrile illness were negative. A lupus ery­ normal. A lumbar puncture was also normal. thematosus preparation was negative as The impression of the neurologist was that were barbiturate and salicylate levels. Spinal metabolic and/or toxic factors were prob­ fluid was unremarkable. Complement fixa­ ably responsible for her central nervous tion for cytomegalic inclusion virus was less system manifestation. than 1:4. The bone marrow showed in­ Starting August 8th. the patient devel-

i

Figure 1 Skin biopsy shows heavy pleomorphic lymphohistiocytic infiltrate within the dermis. Note Pautrier's microabscess and abnormal reticulum cells. X 390 H & E reduced 22%

238 Mycosis Fungoides with Thrombotic Microangiopathy oped numerous clonic convulsions. Anti­ yellowish discoloration and necrosis were convulsant therapy failed to alleviate this noted. condition and the patient expired on August The visceral pleura revealed numerous 11, 1968. petechiae especially over the lower lobes which were firm in consistency. The liver had Autopsy Data multiple small hemangiomata on cross sec­ The patient was a well-developed, well- tion, the largest of these was 1.8 cm in nourished Negro female of 133 pounds. The diameter. The spleen was normal in size skin over the entire body showed numerous and appearance. Gastrointestinal tract, pan­ small and large plaques some of which were creas, genitourinary organs, vascular system hyperpigmented. others hypopigmented and and the skeletal system were unremarkable. several excoriated. These ranged in size from The brain weighed 1250 grams and show­ 0.5 up to 1.0 cm. ed generalized edema with multiple small Abnormal findings in the viscera were as petechial hemorrhages in the left upper parie­ follows: The heart weighed 425 grams and tal cortex. The larger cerebral vessels were appeared to have left ventricular enlarge­ unremarkable. ment. Examination of the valve cusps re­ vealed numerous small rather firm vegeta­ Microscopic Pathology tions on the superior surfaces of mitral and On sections of a few random skin lesions, aortic valves (Fig 2). These vegetations the dermis was composed of an avascular measured, on an average. 0.2 cm in diame­ layer of thick hyalinized connective tissue ter. Throughout the myocardium, several with almost complete loss of dermal ap­ small petechial hemorrhages and areas of pendages. The epidermis showed moderate

Figure 2 Large friable mitral valve vegetations.

239 Chapel, Saeed and Steinhauer hyperkeratosis and parakeratosis with some The underlying endocardium was edema­ flattening of the rete pegs. These sections tous. In the brain the arterioles and capil­ were more representative of the late stages laries of the basal ganglia and the left parie­ of poikiloderma atrophicans vasculare and tal cortex were especially involved by the did not resemble the appearance of mycoses thrombi (Fig 4). Perivascular edema and a seen in earlier surgical biopsy. small parietal lobe infarct were concomitant The most important findings in the viscera findings. Sufficient lesions were found within were the presence of multiple platelet throm­ the basal ganglia, brain stem and cerebrum bi involving the systemic arterioles and capil­ to explain the convulsions which the patient laries. These thrombi were most marked in had exhibited. the heart, kidneys, and the brain, although None of the sections of the viscera showed lungs, liver, spleen, pancreas, and adrenals infiltrates corresponding to mycoses fun­ all showed vascular thrombi to some extent. goides. In the myocardium the thrombi were very extensive and involved most of the capil­ Discussion laries (Fig 3). The capillary walls showed varying degree of endothelial reaction. An Visceral involvement is common in occasional area of myocardial necrosis with MF^ but reports vary greatly as to the polymorphonuclear reaction was found but frequency of dissemination to internal large infarcts were not noted. The endo­ organs. Bluefarb- found visceral metas­ cardial vegetations were composed of plate­ lets and fibrin only, without bacterial growth. tasis to be rare, while GalP reported an

Figure 3

Marked endothelial hyperplasia around fibrin-platelet thrombi. Inflammatory reaction is virtually nonexistent. X 390 H & E reduced 20%

240 Mycosis Fungoides with Thrombotic Microangiopathy

Figure 4 The Virchow-Robinson space around thrombosed cerebral vessels is dilated due to edema fluid. X 390 H & E reduced 20% incidence of 46% ; Cawley et al* found involvement. Although several such an incidence of 80% and Block et aV- cases are included in reviews of dis­ 82%. The nature of the metastatic in­ seminated MF,i' the authors do filtrates varied—some were similar to not describe the nature and extent of that of the primary cutaneous process, the nervous system findings. Riecke,^ while others were indistinguishable Kobner,^ Cawley et al* reported cases from more malignant lymphomatous of MF with metastatic involvement of diseases. the dura mater, but no symptoms re­ The lymph nodes, bone marrow and ferable to the nervous system. Pautrier's spleen are the organs most commonly case" had involvement of the dura and involved in disseminated MF and al­ pia mater and Hemmingson's patientj^" most every organ has exhibited his­ also asymptomatic, had choroid plexus tologic evidence of invasion; however, involvement. metastasis to the central nervous system Breakley, one of the first to report is rare, even in cases with generalized central nervous system involvement in

241 Chapel, Saeed and Steinhauer

a patient with MF, found an infiltrate Necropsy showed multiple foci of de- in the gray and white matter of the myelinization in the brain and cerebel­ cerebral hemispheres.^^ A patient de­ lum and a polymorphous perivascular scribed by Paltaut et aV~ had involve­ inflammatory reaction with numerous ment of the right oculomotor, trigem­ atypical histiocytes throughout the inal and femoral nerves, sparing the brain. The infiltrate was similar to that brain substance. Moncorps et aU^ re­ of the skin lesions. A 1967 CPC from ported the case of a 35-year-old male Barnes Hospital describes a case of MF who developed abnormalities of most in which major neurologic manifesta­ cranial nerves, and increased intra­ tion proved to be due to invasion of cranial pressure several months after the central nervous system by tumor the appearance of cutaneous MF. Nec­ along with focal demyelinization. MF ropsy revealed a cellular infiltrate sim­ and neuromyopathy were reported by ilar to that of the skin about all cranial Kurwa and Payne,^'^ similar to the nerves, the pia mater, corpora quad- association of neuromyopathy with car­ rigemina and left caudate nucleus. cinoma and lymphoma observed by Brandweiner" reported the case of Brain et al.^" The patient, a 67-year- a 50-year-old male who had cutaneous old male, experienced difficulty ascend­ lesions of MF for 30 years. He then ing stairs and rising from a chair almost developed rightsided hemiplegia and simultaneously with the development rightsided deviation of the head and of cutaneous MF. The process rapidly eyes. Needle prick sensation was nor­ progressed, leaving the patient almost mal and Babinsky's sign negative. At bedridden. Shortly before hospitaliza­ autopsy, "hazelnut" to "apple" size tion he awoke with complete paralysis nodules seen within the brain substance of the left hand. Examination revealed were felt to represent metastasis along weakness and wasting of the hand, arm, vessels from the cutaneous process. and leg muscles with fasciculation of The famous physiologist, W. B. the thigh muscles. Autopsy showed Cannon^-'' had a 14-year history of MF. small foci of degeneration of the white He experienced a loss of taste for matter with some loss of anterior horn sweets on the right side of the tongue, cells along the spinal cord and mild together with a rightsided facial paral­ degeneration in the pyramidal tracts. ysis and bilateral deafness. Because No tumor was noted in the central the symptoms responded to irradiation, nervous system or viscera. they were felt to represent neural in­ MF is not frequently associated with vasion. Postmortem examination con­ other disease states. Bluefarb- culled firmed visceral dissemination of the from the Hterature case reports of MF disease but no mention was made of occurring with carcinoma, lupus er­ central nervous system findings. ythematosus, Addison's disease, Ka­ Rosai and Spiro^" presented an in­ posi's sarcoma, leukemia and deep my­ teresting case of a 79-year-old female coses. He did not feel that MF pro­ with a one-year history of MF. She gressed to other lymphomas. However, developed a seventh nerve palsy, left- many authors believe that a mutability sided weakness and increasing lethargy, exists among the lymphomatous di­ but no papilledema and meningismus. seases. Patients with histologically con-

242 Mycosis Fungoides with Thrombotic Microangiopathy firmed MF were reported to undergo myelocytic leukemia, and in two pa­ transition to Hodgkin's disease, lymph­ tients with gastric carcinoma. The osarcoma or reticular cell sarcoma in TTP was the direct cause of death. 34% of the cases collected by Cyr These authors, using the fluorescent et al-" and 16% by Block et aU antibody method, concluded that the The cardinal features of thrombotic thrombi of arterioles and capillaries in thrombocytopenic purpura form a pen­ these cases were composed of platelets tad consisting of thrombocytopenic and fibrin or fibrinogen. purpura, hemolytic anemia, fever, The thrombotic phenomena which neurologic manifestations and renal occur in large veins in association with disease. Diagnosis is confirmed by his­ certain cancers, especially cancer of tologic evidence of widespread hyaline the pancreas, is well known. Although occlusion of terminal arterioles and the incidence of malignant disease with capiflaries. None of these findings are microangiopathy is sufficiently rare that common in patients with mycosis fun­ the possibility of coincidence is strong, goides and there is general agreement this case brings the total number of that MF lacks pathognomonic hema­ reported cases only to six. It is in­ tologic findings.!• -• Anemia, which teresting that many observers regard is not infrequent, is never hemolytic in TTP to be an immunohematologic origin, and platelet counts in MF are or autoimmune disorder which belongs generally normal. to the spectrum of collagen disease like Capillary thrombosis has been ob­ lupus erythematosus and dermatomyo­ served in patients with malignant tu­ sitis.-^-'^ The collagen diseases in turn mors as well as those with acute or have a fairly high incidence of co­ chronic leukemia,-^• but it has not existent neoplasm. Komori-i states that been reported previously in patients any pathogenic relationship between with MF. Thrombotic thrombocyto­ primary malignant disease and TTP penic purpura (TTP) has been reported resembles acquired hemolytic anemia to be associated with systemic lupus ery­ in which idiopathic and symptomatic thematosus, polyarteritis nodosa, malig­ forms occur. nant nephrosclerosis and rheumatism. Summary A few cases were associated with A case is reported of mycosis fun­ malignant tumors, ie, acute myeloid goides with rapid death due to throm­ leukemia and malignant thymoma. A botic thrombocytopenic purpura. The Japanese study reported on observa­ association of these two relatively rare tions of TTP in a patient with acute disorders is reviewed.

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