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A case of lymphomatoid papulosis and Hodgkin's disease
Volume 21 Number 5, Part 2 November 1989
REFERENCES 1. Gilchrest B, Rowe JW, Mihm MC Jr. Bullous dermatosis of hemodialysis. Ann Intern Med 1975;83:480-3. 2. Goldsman GI, Taylor JS. Porphyria cutanea tarda and bullous dermatose.s associated with chronic renal failure: a review. Cleve Clin Q 1983;50:151-61. 3. Webster SB, Dahlberg PJ. Bullous dermatosis of hemodialysis: case report and review of the dermatologic changes in chronic renal failure. Cutis 1980;25:322-6. 4. Gupta AK, Gupta MA, Cardella C J, Haberman HF. Cutaneous associations of chronic renal failure and dialysis. Int J Dermatol 1986;25:498-504. 5. Shelley WB, Elpern D J, Shelley ED. Naprosyn photosensitization demonstrated by challenge. Cutis 1986;38:16970.
Blisters of the fingertips 6. Lichtenstein JR, Babb EJ, Felsher BF. Porphyria cutanea tarda (PCT) in a patient with chronic renal failure on haemodialysis. Br J Dermatol 1981;104:575-8. 7. Palomo-Anellano A, Jimenez-Reyes J, Martin-Moreno L, De Castro-Torres A. Blistering distal dactylitis in an adult. Arch Dermatol 1985;121:1242. 8. CantweU A R Jr, Martz W. Idiopathic bullae in diabetics: bullosis diabeticorum. Arch Dermatol 1967;96:42-4. 9. Matarredona .1, Martin R, De Salamanca RE, et ai. BuUous dermatosis of hemodialysis. J Dermatol (Tokyo) 1985;12:410-5. 10. Jensen JA, Goodson WH, Omachi RS, et al. Subcutaneous tissue oxygen tension falls during hemodialysis. Surgery 1987;101:416-21.
A case of lymphomatoid papulosis and Hodgkin's disease Gabriela Marques Pinto, MD¢ Luis Gon~alves, MD, b Helder Gongalves, MD, a Felicidade Gra~a, MD, c Ana Quental, MD, a Isabel Fonseca, MD, b and Am61ia Monteiro, MD c Lisbon, Portugal Lymphomatoid papulosis is a unique paradoxic entity characterized by recurrent selfhealing papulonodular lesions with histologic features of malignancy. Usually the disease has a protracted benign course; however, it can be associated with or evolve to a lymphoproliferative disorder. Thus "lymphoma-associated papulosis" represents the malignant end of a wide spectrum. We describe a case of a patient with lymphomatoid papulosis who developed Hodgkin's disease 8 years after the onset of skin lesions. Systemic chemotherapy achieved complete remission of Hodgkin's disease, but recurrent papulonodular lesions continued to form in the subsequent 18 months. (J AM ACAD DERMATOL 1989;21: 1051-6.)
In 1968 Macaulay ~ introduced the term lymphomatoid papulosis for a continuing, self-healing papular eruption that was clinically benign and histologically malignant. The eruption consists of recurrent crops of papular and papulonecrotic lesions, often closely resembling those of pityriasis lichenoides et varioliformis acuta (MuchaFrom the Departments of Dermatology" and Pathology,b Curry Cabral Hospital, and the Department of Hematology, Capuchos Hospital? Financial support for color reproduction was provided by Lederle Laboratories of Portugal. Presented in part at the PortugueseSociety of Dermatology Meeting, Lisbon, Portugal, June 20-21, 1987. Reprint requests: Gabriela Marques Pinto, MD, Departamento de Dermatologia, Hospital Curry Cabral, Rua da Benefic~ncia, 1000 Lisboa, Portugal. 16/4/15793
Habermann disease). 24 The histologic finding is papillary or mid-dermal inflammatory infiltrate that contains atypical lymphoid cells in sufficient numbers to suggest a malignant lymphoma. 26 Reviewing the subject, Macaulay 7 suggested that lymphomatoid papulosis is only part of a wide spectrum of "rhythmic paradoxical eruptions." In spite of its alarming pathologic appearance, the disease generally pursues a benign protracted course. However, there have been several reports of the subsequent emergency of systemic lymphomas in patients with lymphomatoid papulosis. 2,3,5-1s In this report the clinicopathologic features of a new case of malignant lymphoma (Hodgkin's disease) complicating lymphomatoid papulosis are described and compared with those of previously reported cases.
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Fig. 1. Multiple papulonodular lesions in various stages of development. Fig. 2. Photomicrograph of lymph node biopsy specimen showing infiltration by lymphocytes, eosinophils, and a Reed-Sternberg cell. (Hematoxylin-eosin stain; X400.) Fig. 3. Photomicrograph of detail of pleomorphic dermal infiltrate showing large, atypical cell that resembles a Reed-Sternberg cell, and atypical lymphoid cell in mitosis. (Hematoxylin-eosin stain; ×400.) Fig. 4. Photomicrograph showing labeling of most atypical lymphoid cells in dermis with anti-helper T cell antibody (OKT4). (Peroxidase-antiperoxidase technique with immunoperoxidase stain; X400.) CASE REPORT
A 37-year-old white man was first seen at our department of dermatology in July 1978 for evaluation of skin lesions of 18 months' duration. The eruption started on the arms and subsequently involved the trunk and legs. The lesions had progressed through several stages; they began as small red papules that enlarged, then crusted, and finally resolved spontaneously within 4 to 6 weeks, leaving a hypopigmented area. Some papules ulcerated and formed hemorrhagic crusts. The lesions were developing and regressing continuously with no disease-free period. Past medical history was noncontributory. On examination the patient was noted to be a healthyappearing man. There were multiple erythematous, papulonodular lesions, 0.5 to 1.0 cm in diameter,
on the trunk and extremities. Some papules were grouped and scaly. Some nodules had necrotic centers, and older lesions had healed with residual hypopigmentation (Fig. 1). The remainder of the results of the physical examination were normal. Results of laboratory studies, including a chest roentgenogram, electrocardiogram, complete blood cell count, blood chemistry studies, protein electrophoresis, erythrocyte sedimentation rate, VDRL test, and urinalysis, were normal. Cultures of thelesions for bacteria and fungi were negative. Biopsy specimens were obtained from three papulonodular lesions on the trunk. Examination of the specimens showed all three lesions had similar pathologic changes that were consistent with the diagnosis of lymphomatoid papulosis.
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Lymphomatoid papulosis and Hodgkin's disease 1053
The patient was reexamined during a 6½-year period; he remained healthy even though new lesions developed periodically. In November 1984, almost 8 years after the onset of the papular eruption, the patient had a weight loss and night sweats. On examination left axillary and bilateral inguinal lymphadenopathies were noted. Examination of a lymph node biopsy specimen showed histologic changes of Hodgldn's disease, mixed-cellularity type (Fig. 2). The lower limb lymphangiogram and the tomography scan of the trunk revealed bilateral mediastinal,//iac, and pelvic lymphadenopathies. The erythrocyte sedimentation rate was 64 mm in the first hour, and the plasma fibrinogen level was 495 mg/dl. Results of the following studies were normal or negative: complete blood cell count, blood chemistry studies to evaluate renal and liver function, protein electrophoresis, immunoglobulin levels, antinuclear antibody, cutaneous delayed-hypersensitivity tests, liver-spleen scan, roentgenogram of the gastrointestinal tract, computed tomography scan of the abdomen, and bone marrow aspirate and biopsy. It was established that the patient had stage III Bb Hodgkin's disease, mixedcellularity type. The patient was treated with nine cycles of therapy by the MOPP combination (mechlorethamine hydrochlofide, vincristine sulfate, procarbazine hydrochloride, prednisone) from May 1985 to July 1986, with complete remission of Hodgkin's disease. During chemotherapy there was considerable improvement of the skin lesions. However, 1 month after the last course of MOPP therapy, multiple papules and nodules reappeared with increased intensity. During the last 18-month period, from August 1986 to December 1987, the patient remained healthy without evidence of extracutaneous disease on complete restaging procedures, but the papulonodular lesions continued to come and go as before. Examination of repeated biopsy specimens of a prominent forearm lesion, taken in February and July 1987, showed pathologic changes similar to those observed in the specimens obtained 9 years before. Observed with light microscopy, the epidermis was normal and the predominant feature was a wedge-shaped, nonepidermotropic, polymorphic cell infiltrate filling the papillary and mid dermis. The infiltrate consisted mainly of lymphocytes, atypical lymphoid cells, and large atypical cells, some multinucleated and closely resembling Reed-Sternberg cells (Fig. 3). Moderate numbers of histiocytes, neutrophils, and eosinophils also were present. Furthermore, immunoperoxidasestudies revealed that 80% of the dermal lymphocyticinfiltrate, including the atypical cells, was reactive with antibodies that define helper/inducer T cells (OKT4) (Fig. 4); only a small proportion (approximately 20%) of lymphocytes reacted with antibodies that
define cytotoxic/suppressor T cells (OKTS). The OKT6 studies revealed an increased number of denditric cells within the epidermis and dermis. Finally, positive reactivity with pan-B was not noted in either large atypical or small lymphoid cells. DISCUSSION Since the first description of lymphomatoid papulosis by Macaulay in 1968,' several cases of this paradoxical entity--clinically benign but histologically malignant--have been reported, some associated with the development of a lymphoreticular malignancy5 3.5-~s In fact, the incidence of lymphomas has been noted in 10% 1° to 19% 13 of patients with lymphomatoid papulosis, suggesting more than a chance concurrence. Among these, at least 10 cases of lymphomatoid papulosis associated with Hodgkin's disease have been reported previously. 7.9-11,13-16 Macaulay, 7 reviewing 59 cases of lymphomatoid papulosis in the literature, found three patients with associated mycosis fungoides and two other patients who developed mycosis fungoides and Hodgkin's disease, respectively. Scheen et al. 9 described two cases of patients with lymphomatoid papulosis in whom Hodgkin's disease and lymphocytic lymphoma, respectively, were ultimately discovered. Weinman and Ackerman 1° reported a case of a 57-year-old man, with lesions since childhood that clinically resembled lymphomatoid papulosis, in whom Hodgkin's disease developed. Dowd et al. '1 described a case of a man with a 20-year history of lymphomatoid papulosis who developed a large cutaneous tumor and regional lymphadenopathy; histologic changes in both skin and lymph node were those of Hodgkin's disease. Sanchez et al. ~3reviewed 31 cases of lymphomatoid papulosis; 6 of the patients developed a lymphoma, including mycosis fungoides, (2 patients), Hodgkin's disease (1), and non-Hodgkin's lymphoma (3). Willemze et al) 4 reported a case of a patient who had Hodgkin's disease involving the paraaortic and parailiac lymph nodes after 25 years of lymphomatoid papulosis. Kadin's study 15 of 15 cases (9 reported previously 19) of lymphomatoid papulosis found (1) two patients in whom Hodgkin's disease developed several years after the onset of lymphomatoid papulosis and whose skin lesions persisted after successful treatment of the lymphoma and (2) two other patients in whom lym-
1054 Pinto et aL phomatoid papulosis skin lesions appeared only after treatment and remission of Hodgkin's disease. Chen and Flare TM reported a case of a man with a 14-year history of lymphomatoid papulosis who developed subcutaneous Hodgkin's disease; the lymphoma remained localized in the subcutis for 10 years before lymph node involvement occurred. Our patient had many similarities to the patients in cases reported previously in which lymphomatold papulosis progressed to a lymphoproliferative disorder. For 8 years he had recurrent crops of lesions clinically and histologically resembling lymphomatoid papulosis, and he was otherwise in good health. Then, systemic symptoms and multiple lymphadenopathies led to the diagnosis of Hodgldn's disease, confirmed by examination of a lymph node biopsy specimen. The lymphoma was treated successfully with MOPP therapy, and there has been no recurrence or other evidence of disease in 18 months of careful observation. Nevertheless, the skin lesions have continued to appear and resolve spontaneously as before. Several cases of benign self-healing Hodgkin's disease confined to the skin were reported in the earlier literature as primary cutaneous Hodgkin's disease?T M Considering the morphologic similarities between the large atypical cells of lymphomatold papulosis and those of Hodgldn's disease, I°,14 some of those eases could probably be diagnosed today as lyrnphomatoid papulosis}6 In fact, skin involvement in Hodgkin's disease usually is associated with advanced preterminal disease and is most often secondary to retrograde lymphatic spread from tumor-involved lymph nodes.~7-29Therefore it is difficult to accept a case with disease limited to skin or with recurrent skin lesions after successful treatment of a lymphoma elsewhere as unequivocal cutaneous Hodgkin's disease, even when ReedSternberg cells are found within the skin infiltrate. 19,29 Thus only the clinical course of the disorder may ultimately establish the distinction of lymphomatoid papulosis from cutaneous Hodgkin's disease} 3,19 The favorable clinical course observed in our patient provided further evidence that he represents another case of lymphoma-associated papulosis in which lymphomatoid papulosis skin lesions appeared severn years before Hodgldrt's disease developed in the lymph nodes and persisted after treatment and remission of the lymphoma. The origin of the atypical cells in lymphomatoid
Journal of the American Academy of Dermatology
papulosis has been controversial. They are claimed to derive from monocyte/macrophage,3° Langerhans' interdigitating reticulum cells,3l and/or inducer/helper T cells.~S,19.32-34Willemze and Scheffer 17iand Willemze et al.31 recognize two major histologic types of lymphomatoid papulosis and strongly contend that they are not distinct entities but, rather, represent the ends of a spectrum: type A (histiocytic) lesions, in which large, atypical cells resembling Reed-Sternberg cells are the principal cellular component; and type B (lymphocytic) lesions, in which cerebriform mononuclear cells with the phenotype of activated helper T cells similar to those observed in the early stages of mycosis fungoides predominate. In our patient the infiltrate observed in all the papulonodular lesion biopsy specimens taken during a 9-year period contained abnormal histiocytoid cells, some resembling Reed-Sternberg cells. On the other hand, examination of the skin biopsy specimens taken in 1987 revealed T lymphocytes of the helper/inducer type within the infiltrate. Thus we found characteristic features of lymphomatoid papulosis type A and some features of type B. Willemze et al? 1 also referred to the presence of transitional forms and of both types in concurrent lesions of lymphomatoid papulosis. It has been hypothesized that the lymphoid cells, on receiving antigenic stimulus, transform into the large atypical Reed-Sternberg-like cells.26 In addition to the reported cases of malignant lymphoma complicating lymphomatoid papulosis, there have been several reports regarding the clinical associations of lymphomatoid papulosis, Hodgkin's disease, and mycosis fungoides.7-13Lederman et al? 5 reported cases of two patients who developed lymphomatoid papulosis 1 and 10 years after diagnosis and therapy for advanced Hodgkin's disease. Kadin 15 and Kadin et al. 19 reported cases of two patients with preceding lymphomatoid papulosis and one case in which the patients transient lesions of lymphomatoid papulosis appeared to evolve into chronic lesions of mycosis fungoides. Fine et al. 3~ also described a case of a patient with lymphomatoid papulosis in whom mycosis fungoides developed. Willemze et al. 31 reported a similar close relation between lymphomatoid papulosis and mycosis fungoides. Furthermore, at least 20 cases of mycosis fungoides associated with Hodgkin's disease have been described in recent years. 15.37-4, The nature of Reed-Sternberg-like cells in lym-
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Lymphomatoid papulosis and Hodgkin's disease 1055
phomatoid papulosis and the unexpectedly frequent clinical associations of lymphomatoid papulosis, Hodgkin's disease, and mycosis fungoides have been clarified by Kadin 15 arid Kadin et al., j9 who proposed a common activated helper T cell origin for those disorders. They found a spectrum of activated T4-positive cells, including cerebriform cells and large transformed Reed-Sternberg-like cells, within the lymphomatoid papulosis skin infiltrate. In view of this fact, they suggested that clonal expansion of the cerebfiform cells leads to mycosis fungoides and similar expansion of the ReedSternberg-like cells results in Hodgkin's disease. Support of this hypothesis is provided by recent studies regarding the immunophenotype of the large atypical cells of lymphomatoid papulosis. 42"47 It appears that these cel/s express Ki-1 and activation-associated antigens while showing the variable pattern of T cell antigen expression. Therefore the subsequent development of Hodgkin's disease in some patients with lymphomatoid papulosis could be taken as an indication that the atypical cells proceed in their differentiation to a degree of activation closely related, or even identical, to that of Hodgkin's and Reed-Sternberg cells. Further correlations of cell phenotype and clinical course may help to predict which patients with lymphomatoid papulosis will eventually develop mycosis fungoides and Hodgkin's disease. Moreover, the progression of lymphomatoid papulosis to lymphoma m a y involve the lessening of host resistance or the acquisition of one or more mutations in clonal T cells, allowing them to overcome the host response,4S, 47 In conclusion, the diagnosis of cutaneous Hodgkin's disease should be made cautiously because it may be mistaken for or be associated with lymphomatoid papulosis. On the other hand, all patients with lymphomatoid papulosis require long-term follow-up, because they m a y develop actual malignancy. REFERENCES 1. Macaulay WL. Lymphomatoid papulosis: a continuing self-healing eruption, clinically benign--histologically malignant. Arch Dermatol 1968;97:23-30, 2. Kawada A, Anekoji K, Miyamoto M, Nakai T, Moris S, Unusual manifestation of malignant reticulosis of the skin: cutaneous lesions simulating parapsoriasis guttata. Dermatologica 1969;138:369-78. 3, Black MM, Wilson Jones E. "Lymphomatoid" pityriasis lichenoldes: a variant with histological features simulating a lymphoma--a clinical and histopathological study of 15 cases with details of long term follow up. Br J Dermatol 1972;86:329-47.
4. Valentino LA, Hclwig EG. Lymphomatoid papulosis. Arch Pathol 1973;96:409-16, 5. Dupont A. Transformation maligne trrs tardive d'une rrticulose papuleuse/t 6volution prolong& (lymphomatoid papulosis). Ann Dermatol Syph 1973;I00:141-6. 6. Brehmer-Andersson E. Mycosis fungoides and its relation to Srzary's syndrome, lymphomatoid papulosis, and primary cutaneous Hodgkin's disease: a clinical, histopathologic and cytologic study of fourteen cases and a critical review of the literature. Aeta Derm Venereol (Stockh) [suppl] 1976;75:1-142. 7. Macaulay WL. Lymphomatoid papulosis, Int J Dermatol 1978;17:204-12. 8. Messenger AG, Marshall TL, Summerly R. A case of lymphomatoid papulosis and systemic lymphoma. Br J Dermatol 1981;104:77-82. 9. Scheen SR III, Doyle JA, Winklemann RK, Lymphomaassociated papulosis: lymphomatoid papulosis associated with lymphoma. J AM ACADDF.RMATOL1981;4:45l-7. 10. Weinman V, Aekerman AB. Lymphomatoid papulosis: a critical review and new findings. Am J DermatopathoI 1981;3:129-63. 11. Dowd PM, Munro DD, Stansfeld AG. Lymphomatoid papulosis and primary cutaneous Hodgkin's disease. J R Soc Med 1981;74:68-71. 12. Sina B, Burnett JW. Lymphomatoid papulosis: case report and literature review. Arch Dermatol 1983; ]19:189-97. 13. Sanchez NP, Pittelkow MR, Muller SA, et aL The clinicopathologic spectrum of lymphomatoid papulosis: study of 31 cases. J AM ACADDERMATOL1983;8:81-94. 14. Willemze R, Scheffer E, Ruiter D J, et al. Lymphomatoid papulosis and Hodgkin's disease: are they related? Arch Dermatol Res 1983;275:159-67. 15. Kadin ME. Common activated helper T-cell origin for lymphomatoid papulosis, mycosis fungoides, and some types of Hodgkin's disease. Lancet 1985;2:864-5, 16. Chen KTK, Flare MS. Hodgkin's disease complicating lymphomatoid papulosis. Am J Dermatopathol 1985; 7:555-61. 17. Witlemze R, Scheffer E. Clinical and histological differentiation between lymphomatoid papulosis and pityriasis lichenoides. J AM ACADDERMATOI.1985;13:418-28. 18. Lange-Wantzin G, Thomsen K, Branrup F, et al. Lymphomatoid papulosis: development into cutaneous T-cell lymphoma. Arch Dermatol 1985;121:792-4. 19. Kadin M, Nasu K, Sako D, Said J, Vanderheid E. Lymphomatoid papulosis: a cutaneous proliferation of activated helper T cells expressing Hodgkin's diseaseassociated antigens, Am J Pathol 1985;119:315-25. 20. Van der Meiren L. Three cases of Hodgkin's disease with predominantly cutaneous localization, Br J Dermatol 1948;60:181-4, 21. Rotter B, Liebner E, Aram H. Hodgldn's disease: cutaneous nodules preceding systematization. Cutis 1968;4: 415-9. 22. Szur L, Levene GM, Harrison CV, Samman PD. Primary cutaneous Hodgkin's disease. Lancet 1970;1:1016-20. 23. Rubins J. Cutaneous Hodgkin's disease: indolent course and control with chemotherapy. Cancer 1978;42:121921, 24. Gordon RA, Lookingbill DP, Abt AB. Skin infiltration in Hodgkin's disease. Arch Dermatol 1980;116:1038-40. 25. Silverman CL, Strayer DS, Wasserman TH. Cutaneous Hodgkin's disease. Arch Dermatol 1982;118:918-21. 26. Tokura Y, Takigawa M, Oku T, Yamada M. Lymphomatoid papulosis. Arch Dermatol 1986;122:1400-5.
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27. Benninghoff DL, Medina A, Alexander LL, Camiel MR. The mode of spread of Hodgkin's disease to the skin. Cancer 1970;26:1135-40. 28. Smith JL Jr, Butter J J. Skin involvement in Hodgkin's disease. Cancer 1980;45:354-61. 29. White RM, Patterson JW. Cutaneous involvement in Hodgkin's disease. Cancer 1985;55:1136-45. 30. Poppema S, Van Voorst Vader PC, Rozeboom-Uiterwijk T, Dijkstra JWE. Lymphomatoid papulosis: case report providing evidence for a monocyte-macrophage origin of the atypical cells. Cancer 1983;52:1178-82. 31. Willemze R, Scheffer E, Ruiter D J, et al. Immunological, cytochernical and ultra-struotural studies in lymphomatoid paputosis. Br J Dermatol 1983;108:381-94. 32. Burg G, Hoffmann-Fezer G, Nikolowski J, et al. Lymphomatoid papulosis: a cutaneous T-ceU pseudolymphoma. Acta Derm Venereol (Stock_h) 1981;61:491-6. 33. Harrist T J, Bhan AK, Murphy GF, et al. Lymphomatoid papulosis and lymphomatoid granulomatosis: T cell subset populations, refined light microscopic morphology and direct immunoftuorescence observations [Abstract]. J Invest Dermatol 1981;76:326. 34. Espinoza CG. Erkman-Balis B. Fenske NA. Lyrnphomatold papulosis: a premalignant T cell disorder. J AM ACAD DERMATOU1985;13:736-43. 35. Lederman JS, Sober AJ, Harrist T J, Lederman GS. Lymphomatoid papulosis following Hodgkin's disease. J AM ACAD DERMATOL1987;16:331-5. 36. Fine RM, Meltzer HD, Rudner EJ. Lymphomatoid papulosis eventuating in mycosis fungoides. South Med J 1974;67:1492-7. 37. Chart WC, Griem ML, Grozea PN, et al. Mycosis fungoides and Hodgkin's disease occurring in the same patient: report of three cases. Cancer 1979;44: I408-13. 38. Hawkins KA, Schinella R, Schwartz M, et al. Simultaneous occurrence of mycosis fungoides and Hodgkin's disease. Am J Hematol 1983;14:355-62.
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39. Clement M, Monk M, Pembroke AC, Bhakri H, Pettingale KW, der Vivien A. Mycosis fungoides and Hodgldn's disease. J R Soc Med 1984;77:1037-9. 40. Caya JG, Choi H, Tieu TM, Wollenberg NL, Almagro UA. Hodgldn's disease followed by mycosis fungoides in the same patient: case report and literature review. Cancer 1984;53:463-7. 41. Scheen SR, Banks PM, Winkelmann RK. Morphologic heterogeneity of malignant lymphomas developing in mycosis fungoides. Mayo Clin Proc 1984;59:95-106. 42. Stein H, Mason DY, Gerdes J, O'Connor N, Wainscoat J, Pollesen G. The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. Blood 1985:66:848-58. 43. Ralfldaer E, Stein H, Wantzin GL, et al. Lymphomatoid papulosis: characterization of skin infiltrates by monoclonal antibodies. Am J Clin Pathol 1985;84:587-93. 44. Wood GS, Striclder JG, Deneau DG, Egbert B, Warnke RA. Lymphomatoid papulosis expresses immunophenotypes associated with T cell lymphoma but not inflammation. J AM ACADDERMATOL1986;15:444-58. 45. Kaudewitz P, Stein H, Burg G, Mason DY, Braun-Falco O. Atypical cells in lymphomatoid papulosis express the Hodgkin's cell-associated antigen Ki-1. J Invest Dermatol 1986;86:350-4. 46. Weiss LM, Wood GS, Trela M, et al. Clonal T-cell populations in lymphomatoid papulosis: evidence of a lymphoproliferative origin for a clinically benign disease. N Engl J Med 1986;315:475-9. 47. Wood GS, Strickler JG, Abel EA, Deneau DG, Warnke RA. Immunohistology of pityriasis lichenoides et variliformis acuta and pityriasis lichenoides chronica: evidence for their interrelationship with lymphomatoid papulosis. J AM ACAD DE•MATOL 1987;16:559-70.
REFERENCES 1. Gilchrest B, Rowe JW, Mihm MC Jr. Bullous dermatosis of hemodialysis. Ann Intern Med 1975;83:480-3. 2. Goldsman GI, Taylor JS. Porphyria cutanea tarda and bullous dermatose.s associated with chronic renal failure: a review. Cleve Clin Q 1983;50:151-61. 3. Webster SB, Dahlberg PJ. Bullous dermatosis of hemodialysis: case report and review of the dermatologic changes in chronic renal failure. Cutis 1980;25:322-6. 4. Gupta AK, Gupta MA, Cardella C J, Haberman HF. Cutaneous associations of chronic renal failure and dialysis. Int J Dermatol 1986;25:498-504. 5. Shelley WB, Elpern D J, Shelley ED. Naprosyn photosensitization demonstrated by challenge. Cutis 1986;38:16970.
Blisters of the fingertips 6. Lichtenstein JR, Babb EJ, Felsher BF. Porphyria cutanea tarda (PCT) in a patient with chronic renal failure on haemodialysis. Br J Dermatol 1981;104:575-8. 7. Palomo-Anellano A, Jimenez-Reyes J, Martin-Moreno L, De Castro-Torres A. Blistering distal dactylitis in an adult. Arch Dermatol 1985;121:1242. 8. CantweU A R Jr, Martz W. Idiopathic bullae in diabetics: bullosis diabeticorum. Arch Dermatol 1967;96:42-4. 9. Matarredona .1, Martin R, De Salamanca RE, et ai. BuUous dermatosis of hemodialysis. J Dermatol (Tokyo) 1985;12:410-5. 10. Jensen JA, Goodson WH, Omachi RS, et al. Subcutaneous tissue oxygen tension falls during hemodialysis. Surgery 1987;101:416-21.
A case of lymphomatoid papulosis and Hodgkin's disease Gabriela Marques Pinto, MD¢ Luis Gon~alves, MD, b Helder Gongalves, MD, a Felicidade Gra~a, MD, c Ana Quental, MD, a Isabel Fonseca, MD, b and Am61ia Monteiro, MD c Lisbon, Portugal Lymphomatoid papulosis is a unique paradoxic entity characterized by recurrent selfhealing papulonodular lesions with histologic features of malignancy. Usually the disease has a protracted benign course; however, it can be associated with or evolve to a lymphoproliferative disorder. Thus "lymphoma-associated papulosis" represents the malignant end of a wide spectrum. We describe a case of a patient with lymphomatoid papulosis who developed Hodgkin's disease 8 years after the onset of skin lesions. Systemic chemotherapy achieved complete remission of Hodgkin's disease, but recurrent papulonodular lesions continued to form in the subsequent 18 months. (J AM ACAD DERMATOL 1989;21: 1051-6.)
In 1968 Macaulay ~ introduced the term lymphomatoid papulosis for a continuing, self-healing papular eruption that was clinically benign and histologically malignant. The eruption consists of recurrent crops of papular and papulonecrotic lesions, often closely resembling those of pityriasis lichenoides et varioliformis acuta (MuchaFrom the Departments of Dermatology" and Pathology,b Curry Cabral Hospital, and the Department of Hematology, Capuchos Hospital? Financial support for color reproduction was provided by Lederle Laboratories of Portugal. Presented in part at the PortugueseSociety of Dermatology Meeting, Lisbon, Portugal, June 20-21, 1987. Reprint requests: Gabriela Marques Pinto, MD, Departamento de Dermatologia, Hospital Curry Cabral, Rua da Benefic~ncia, 1000 Lisboa, Portugal. 16/4/15793
Habermann disease). 24 The histologic finding is papillary or mid-dermal inflammatory infiltrate that contains atypical lymphoid cells in sufficient numbers to suggest a malignant lymphoma. 26 Reviewing the subject, Macaulay 7 suggested that lymphomatoid papulosis is only part of a wide spectrum of "rhythmic paradoxical eruptions." In spite of its alarming pathologic appearance, the disease generally pursues a benign protracted course. However, there have been several reports of the subsequent emergency of systemic lymphomas in patients with lymphomatoid papulosis. 2,3,5-1s In this report the clinicopathologic features of a new case of malignant lymphoma (Hodgkin's disease) complicating lymphomatoid papulosis are described and compared with those of previously reported cases.
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Fig. 1. Multiple papulonodular lesions in various stages of development. Fig. 2. Photomicrograph of lymph node biopsy specimen showing infiltration by lymphocytes, eosinophils, and a Reed-Sternberg cell. (Hematoxylin-eosin stain; X400.) Fig. 3. Photomicrograph of detail of pleomorphic dermal infiltrate showing large, atypical cell that resembles a Reed-Sternberg cell, and atypical lymphoid cell in mitosis. (Hematoxylin-eosin stain; ×400.) Fig. 4. Photomicrograph showing labeling of most atypical lymphoid cells in dermis with anti-helper T cell antibody (OKT4). (Peroxidase-antiperoxidase technique with immunoperoxidase stain; X400.) CASE REPORT
A 37-year-old white man was first seen at our department of dermatology in July 1978 for evaluation of skin lesions of 18 months' duration. The eruption started on the arms and subsequently involved the trunk and legs. The lesions had progressed through several stages; they began as small red papules that enlarged, then crusted, and finally resolved spontaneously within 4 to 6 weeks, leaving a hypopigmented area. Some papules ulcerated and formed hemorrhagic crusts. The lesions were developing and regressing continuously with no disease-free period. Past medical history was noncontributory. On examination the patient was noted to be a healthyappearing man. There were multiple erythematous, papulonodular lesions, 0.5 to 1.0 cm in diameter,
on the trunk and extremities. Some papules were grouped and scaly. Some nodules had necrotic centers, and older lesions had healed with residual hypopigmentation (Fig. 1). The remainder of the results of the physical examination were normal. Results of laboratory studies, including a chest roentgenogram, electrocardiogram, complete blood cell count, blood chemistry studies, protein electrophoresis, erythrocyte sedimentation rate, VDRL test, and urinalysis, were normal. Cultures of thelesions for bacteria and fungi were negative. Biopsy specimens were obtained from three papulonodular lesions on the trunk. Examination of the specimens showed all three lesions had similar pathologic changes that were consistent with the diagnosis of lymphomatoid papulosis.
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Lymphomatoid papulosis and Hodgkin's disease 1053
The patient was reexamined during a 6½-year period; he remained healthy even though new lesions developed periodically. In November 1984, almost 8 years after the onset of the papular eruption, the patient had a weight loss and night sweats. On examination left axillary and bilateral inguinal lymphadenopathies were noted. Examination of a lymph node biopsy specimen showed histologic changes of Hodgldn's disease, mixed-cellularity type (Fig. 2). The lower limb lymphangiogram and the tomography scan of the trunk revealed bilateral mediastinal,//iac, and pelvic lymphadenopathies. The erythrocyte sedimentation rate was 64 mm in the first hour, and the plasma fibrinogen level was 495 mg/dl. Results of the following studies were normal or negative: complete blood cell count, blood chemistry studies to evaluate renal and liver function, protein electrophoresis, immunoglobulin levels, antinuclear antibody, cutaneous delayed-hypersensitivity tests, liver-spleen scan, roentgenogram of the gastrointestinal tract, computed tomography scan of the abdomen, and bone marrow aspirate and biopsy. It was established that the patient had stage III Bb Hodgkin's disease, mixedcellularity type. The patient was treated with nine cycles of therapy by the MOPP combination (mechlorethamine hydrochlofide, vincristine sulfate, procarbazine hydrochloride, prednisone) from May 1985 to July 1986, with complete remission of Hodgkin's disease. During chemotherapy there was considerable improvement of the skin lesions. However, 1 month after the last course of MOPP therapy, multiple papules and nodules reappeared with increased intensity. During the last 18-month period, from August 1986 to December 1987, the patient remained healthy without evidence of extracutaneous disease on complete restaging procedures, but the papulonodular lesions continued to come and go as before. Examination of repeated biopsy specimens of a prominent forearm lesion, taken in February and July 1987, showed pathologic changes similar to those observed in the specimens obtained 9 years before. Observed with light microscopy, the epidermis was normal and the predominant feature was a wedge-shaped, nonepidermotropic, polymorphic cell infiltrate filling the papillary and mid dermis. The infiltrate consisted mainly of lymphocytes, atypical lymphoid cells, and large atypical cells, some multinucleated and closely resembling Reed-Sternberg cells (Fig. 3). Moderate numbers of histiocytes, neutrophils, and eosinophils also were present. Furthermore, immunoperoxidasestudies revealed that 80% of the dermal lymphocyticinfiltrate, including the atypical cells, was reactive with antibodies that define helper/inducer T cells (OKT4) (Fig. 4); only a small proportion (approximately 20%) of lymphocytes reacted with antibodies that
define cytotoxic/suppressor T cells (OKTS). The OKT6 studies revealed an increased number of denditric cells within the epidermis and dermis. Finally, positive reactivity with pan-B was not noted in either large atypical or small lymphoid cells. DISCUSSION Since the first description of lymphomatoid papulosis by Macaulay in 1968,' several cases of this paradoxical entity--clinically benign but histologically malignant--have been reported, some associated with the development of a lymphoreticular malignancy5 3.5-~s In fact, the incidence of lymphomas has been noted in 10% 1° to 19% 13 of patients with lymphomatoid papulosis, suggesting more than a chance concurrence. Among these, at least 10 cases of lymphomatoid papulosis associated with Hodgkin's disease have been reported previously. 7.9-11,13-16 Macaulay, 7 reviewing 59 cases of lymphomatoid papulosis in the literature, found three patients with associated mycosis fungoides and two other patients who developed mycosis fungoides and Hodgkin's disease, respectively. Scheen et al. 9 described two cases of patients with lymphomatoid papulosis in whom Hodgkin's disease and lymphocytic lymphoma, respectively, were ultimately discovered. Weinman and Ackerman 1° reported a case of a 57-year-old man, with lesions since childhood that clinically resembled lymphomatoid papulosis, in whom Hodgkin's disease developed. Dowd et al. '1 described a case of a man with a 20-year history of lymphomatoid papulosis who developed a large cutaneous tumor and regional lymphadenopathy; histologic changes in both skin and lymph node were those of Hodgkin's disease. Sanchez et al. ~3reviewed 31 cases of lymphomatoid papulosis; 6 of the patients developed a lymphoma, including mycosis fungoides, (2 patients), Hodgkin's disease (1), and non-Hodgkin's lymphoma (3). Willemze et al) 4 reported a case of a patient who had Hodgkin's disease involving the paraaortic and parailiac lymph nodes after 25 years of lymphomatoid papulosis. Kadin's study 15 of 15 cases (9 reported previously 19) of lymphomatoid papulosis found (1) two patients in whom Hodgkin's disease developed several years after the onset of lymphomatoid papulosis and whose skin lesions persisted after successful treatment of the lymphoma and (2) two other patients in whom lym-
1054 Pinto et aL phomatoid papulosis skin lesions appeared only after treatment and remission of Hodgkin's disease. Chen and Flare TM reported a case of a man with a 14-year history of lymphomatoid papulosis who developed subcutaneous Hodgkin's disease; the lymphoma remained localized in the subcutis for 10 years before lymph node involvement occurred. Our patient had many similarities to the patients in cases reported previously in which lymphomatold papulosis progressed to a lymphoproliferative disorder. For 8 years he had recurrent crops of lesions clinically and histologically resembling lymphomatoid papulosis, and he was otherwise in good health. Then, systemic symptoms and multiple lymphadenopathies led to the diagnosis of Hodgldn's disease, confirmed by examination of a lymph node biopsy specimen. The lymphoma was treated successfully with MOPP therapy, and there has been no recurrence or other evidence of disease in 18 months of careful observation. Nevertheless, the skin lesions have continued to appear and resolve spontaneously as before. Several cases of benign self-healing Hodgkin's disease confined to the skin were reported in the earlier literature as primary cutaneous Hodgkin's disease?T M Considering the morphologic similarities between the large atypical cells of lymphomatold papulosis and those of Hodgldn's disease, I°,14 some of those eases could probably be diagnosed today as lyrnphomatoid papulosis}6 In fact, skin involvement in Hodgkin's disease usually is associated with advanced preterminal disease and is most often secondary to retrograde lymphatic spread from tumor-involved lymph nodes.~7-29Therefore it is difficult to accept a case with disease limited to skin or with recurrent skin lesions after successful treatment of a lymphoma elsewhere as unequivocal cutaneous Hodgkin's disease, even when ReedSternberg cells are found within the skin infiltrate. 19,29 Thus only the clinical course of the disorder may ultimately establish the distinction of lymphomatoid papulosis from cutaneous Hodgkin's disease} 3,19 The favorable clinical course observed in our patient provided further evidence that he represents another case of lymphoma-associated papulosis in which lymphomatoid papulosis skin lesions appeared severn years before Hodgldrt's disease developed in the lymph nodes and persisted after treatment and remission of the lymphoma. The origin of the atypical cells in lymphomatoid
Journal of the American Academy of Dermatology
papulosis has been controversial. They are claimed to derive from monocyte/macrophage,3° Langerhans' interdigitating reticulum cells,3l and/or inducer/helper T cells.~S,19.32-34Willemze and Scheffer 17iand Willemze et al.31 recognize two major histologic types of lymphomatoid papulosis and strongly contend that they are not distinct entities but, rather, represent the ends of a spectrum: type A (histiocytic) lesions, in which large, atypical cells resembling Reed-Sternberg cells are the principal cellular component; and type B (lymphocytic) lesions, in which cerebriform mononuclear cells with the phenotype of activated helper T cells similar to those observed in the early stages of mycosis fungoides predominate. In our patient the infiltrate observed in all the papulonodular lesion biopsy specimens taken during a 9-year period contained abnormal histiocytoid cells, some resembling Reed-Sternberg cells. On the other hand, examination of the skin biopsy specimens taken in 1987 revealed T lymphocytes of the helper/inducer type within the infiltrate. Thus we found characteristic features of lymphomatoid papulosis type A and some features of type B. Willemze et al? 1 also referred to the presence of transitional forms and of both types in concurrent lesions of lymphomatoid papulosis. It has been hypothesized that the lymphoid cells, on receiving antigenic stimulus, transform into the large atypical Reed-Sternberg-like cells.26 In addition to the reported cases of malignant lymphoma complicating lymphomatoid papulosis, there have been several reports regarding the clinical associations of lymphomatoid papulosis, Hodgkin's disease, and mycosis fungoides.7-13Lederman et al? 5 reported cases of two patients who developed lymphomatoid papulosis 1 and 10 years after diagnosis and therapy for advanced Hodgkin's disease. Kadin 15 and Kadin et al. 19 reported cases of two patients with preceding lymphomatoid papulosis and one case in which the patients transient lesions of lymphomatoid papulosis appeared to evolve into chronic lesions of mycosis fungoides. Fine et al. 3~ also described a case of a patient with lymphomatoid papulosis in whom mycosis fungoides developed. Willemze et al. 31 reported a similar close relation between lymphomatoid papulosis and mycosis fungoides. Furthermore, at least 20 cases of mycosis fungoides associated with Hodgkin's disease have been described in recent years. 15.37-4, The nature of Reed-Sternberg-like cells in lym-
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Lymphomatoid papulosis and Hodgkin's disease 1055
phomatoid papulosis and the unexpectedly frequent clinical associations of lymphomatoid papulosis, Hodgkin's disease, and mycosis fungoides have been clarified by Kadin 15 arid Kadin et al., j9 who proposed a common activated helper T cell origin for those disorders. They found a spectrum of activated T4-positive cells, including cerebriform cells and large transformed Reed-Sternberg-like cells, within the lymphomatoid papulosis skin infiltrate. In view of this fact, they suggested that clonal expansion of the cerebfiform cells leads to mycosis fungoides and similar expansion of the ReedSternberg-like cells results in Hodgkin's disease. Support of this hypothesis is provided by recent studies regarding the immunophenotype of the large atypical cells of lymphomatoid papulosis. 42"47 It appears that these cel/s express Ki-1 and activation-associated antigens while showing the variable pattern of T cell antigen expression. Therefore the subsequent development of Hodgkin's disease in some patients with lymphomatoid papulosis could be taken as an indication that the atypical cells proceed in their differentiation to a degree of activation closely related, or even identical, to that of Hodgkin's and Reed-Sternberg cells. Further correlations of cell phenotype and clinical course may help to predict which patients with lymphomatoid papulosis will eventually develop mycosis fungoides and Hodgkin's disease. Moreover, the progression of lymphomatoid papulosis to lymphoma m a y involve the lessening of host resistance or the acquisition of one or more mutations in clonal T cells, allowing them to overcome the host response,4S, 47 In conclusion, the diagnosis of cutaneous Hodgkin's disease should be made cautiously because it may be mistaken for or be associated with lymphomatoid papulosis. On the other hand, all patients with lymphomatoid papulosis require long-term follow-up, because they m a y develop actual malignancy. REFERENCES 1. Macaulay WL. Lymphomatoid papulosis: a continuing self-healing eruption, clinically benign--histologically malignant. Arch Dermatol 1968;97:23-30, 2. Kawada A, Anekoji K, Miyamoto M, Nakai T, Moris S, Unusual manifestation of malignant reticulosis of the skin: cutaneous lesions simulating parapsoriasis guttata. Dermatologica 1969;138:369-78. 3, Black MM, Wilson Jones E. "Lymphomatoid" pityriasis lichenoldes: a variant with histological features simulating a lymphoma--a clinical and histopathological study of 15 cases with details of long term follow up. Br J Dermatol 1972;86:329-47.
4. Valentino LA, Hclwig EG. Lymphomatoid papulosis. Arch Pathol 1973;96:409-16, 5. Dupont A. Transformation maligne trrs tardive d'une rrticulose papuleuse/t 6volution prolong& (lymphomatoid papulosis). Ann Dermatol Syph 1973;I00:141-6. 6. Brehmer-Andersson E. Mycosis fungoides and its relation to Srzary's syndrome, lymphomatoid papulosis, and primary cutaneous Hodgkin's disease: a clinical, histopathologic and cytologic study of fourteen cases and a critical review of the literature. Aeta Derm Venereol (Stockh) [suppl] 1976;75:1-142. 7. Macaulay WL. Lymphomatoid papulosis, Int J Dermatol 1978;17:204-12. 8. Messenger AG, Marshall TL, Summerly R. A case of lymphomatoid papulosis and systemic lymphoma. Br J Dermatol 1981;104:77-82. 9. Scheen SR III, Doyle JA, Winklemann RK, Lymphomaassociated papulosis: lymphomatoid papulosis associated with lymphoma. J AM ACADDF.RMATOL1981;4:45l-7. 10. Weinman V, Aekerman AB. Lymphomatoid papulosis: a critical review and new findings. Am J DermatopathoI 1981;3:129-63. 11. Dowd PM, Munro DD, Stansfeld AG. Lymphomatoid papulosis and primary cutaneous Hodgkin's disease. J R Soc Med 1981;74:68-71. 12. Sina B, Burnett JW. Lymphomatoid papulosis: case report and literature review. Arch Dermatol 1983; ]19:189-97. 13. Sanchez NP, Pittelkow MR, Muller SA, et aL The clinicopathologic spectrum of lymphomatoid papulosis: study of 31 cases. J AM ACADDERMATOL1983;8:81-94. 14. Willemze R, Scheffer E, Ruiter D J, et al. Lymphomatoid papulosis and Hodgkin's disease: are they related? Arch Dermatol Res 1983;275:159-67. 15. Kadin ME. Common activated helper T-cell origin for lymphomatoid papulosis, mycosis fungoides, and some types of Hodgkin's disease. Lancet 1985;2:864-5, 16. Chen KTK, Flare MS. Hodgkin's disease complicating lymphomatoid papulosis. Am J Dermatopathol 1985; 7:555-61. 17. Witlemze R, Scheffer E. Clinical and histological differentiation between lymphomatoid papulosis and pityriasis lichenoides. J AM ACADDERMATOI.1985;13:418-28. 18. Lange-Wantzin G, Thomsen K, Branrup F, et al. Lymphomatoid papulosis: development into cutaneous T-cell lymphoma. Arch Dermatol 1985;121:792-4. 19. Kadin M, Nasu K, Sako D, Said J, Vanderheid E. Lymphomatoid papulosis: a cutaneous proliferation of activated helper T cells expressing Hodgkin's diseaseassociated antigens, Am J Pathol 1985;119:315-25. 20. Van der Meiren L. Three cases of Hodgkin's disease with predominantly cutaneous localization, Br J Dermatol 1948;60:181-4, 21. Rotter B, Liebner E, Aram H. Hodgldn's disease: cutaneous nodules preceding systematization. Cutis 1968;4: 415-9. 22. Szur L, Levene GM, Harrison CV, Samman PD. Primary cutaneous Hodgkin's disease. Lancet 1970;1:1016-20. 23. Rubins J. Cutaneous Hodgkin's disease: indolent course and control with chemotherapy. Cancer 1978;42:121921, 24. Gordon RA, Lookingbill DP, Abt AB. Skin infiltration in Hodgkin's disease. Arch Dermatol 1980;116:1038-40. 25. Silverman CL, Strayer DS, Wasserman TH. Cutaneous Hodgkin's disease. Arch Dermatol 1982;118:918-21. 26. Tokura Y, Takigawa M, Oku T, Yamada M. Lymphomatoid papulosis. Arch Dermatol 1986;122:1400-5.
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27. Benninghoff DL, Medina A, Alexander LL, Camiel MR. The mode of spread of Hodgkin's disease to the skin. Cancer 1970;26:1135-40. 28. Smith JL Jr, Butter J J. Skin involvement in Hodgkin's disease. Cancer 1980;45:354-61. 29. White RM, Patterson JW. Cutaneous involvement in Hodgkin's disease. Cancer 1985;55:1136-45. 30. Poppema S, Van Voorst Vader PC, Rozeboom-Uiterwijk T, Dijkstra JWE. Lymphomatoid papulosis: case report providing evidence for a monocyte-macrophage origin of the atypical cells. Cancer 1983;52:1178-82. 31. Willemze R, Scheffer E, Ruiter D J, et al. Immunological, cytochernical and ultra-struotural studies in lymphomatoid paputosis. Br J Dermatol 1983;108:381-94. 32. Burg G, Hoffmann-Fezer G, Nikolowski J, et al. Lymphomatoid papulosis: a cutaneous T-ceU pseudolymphoma. Acta Derm Venereol (Stock_h) 1981;61:491-6. 33. Harrist T J, Bhan AK, Murphy GF, et al. Lymphomatoid papulosis and lymphomatoid granulomatosis: T cell subset populations, refined light microscopic morphology and direct immunoftuorescence observations [Abstract]. J Invest Dermatol 1981;76:326. 34. Espinoza CG. Erkman-Balis B. Fenske NA. Lyrnphomatold papulosis: a premalignant T cell disorder. J AM ACAD DERMATOU1985;13:736-43. 35. Lederman JS, Sober AJ, Harrist T J, Lederman GS. Lymphomatoid papulosis following Hodgkin's disease. J AM ACAD DERMATOL1987;16:331-5. 36. Fine RM, Meltzer HD, Rudner EJ. Lymphomatoid papulosis eventuating in mycosis fungoides. South Med J 1974;67:1492-7. 37. Chart WC, Griem ML, Grozea PN, et al. Mycosis fungoides and Hodgkin's disease occurring in the same patient: report of three cases. Cancer 1979;44: I408-13. 38. Hawkins KA, Schinella R, Schwartz M, et al. Simultaneous occurrence of mycosis fungoides and Hodgkin's disease. Am J Hematol 1983;14:355-62.
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39. Clement M, Monk M, Pembroke AC, Bhakri H, Pettingale KW, der Vivien A. Mycosis fungoides and Hodgldn's disease. J R Soc Med 1984;77:1037-9. 40. Caya JG, Choi H, Tieu TM, Wollenberg NL, Almagro UA. Hodgldn's disease followed by mycosis fungoides in the same patient: case report and literature review. Cancer 1984;53:463-7. 41. Scheen SR, Banks PM, Winkelmann RK. Morphologic heterogeneity of malignant lymphomas developing in mycosis fungoides. Mayo Clin Proc 1984;59:95-106. 42. Stein H, Mason DY, Gerdes J, O'Connor N, Wainscoat J, Pollesen G. The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. Blood 1985:66:848-58. 43. Ralfldaer E, Stein H, Wantzin GL, et al. Lymphomatoid papulosis: characterization of skin infiltrates by monoclonal antibodies. Am J Clin Pathol 1985;84:587-93. 44. Wood GS, Striclder JG, Deneau DG, Egbert B, Warnke RA. Lymphomatoid papulosis expresses immunophenotypes associated with T cell lymphoma but not inflammation. J AM ACADDERMATOL1986;15:444-58. 45. Kaudewitz P, Stein H, Burg G, Mason DY, Braun-Falco O. Atypical cells in lymphomatoid papulosis express the Hodgkin's cell-associated antigen Ki-1. J Invest Dermatol 1986;86:350-4. 46. Weiss LM, Wood GS, Trela M, et al. Clonal T-cell populations in lymphomatoid papulosis: evidence of a lymphoproliferative origin for a clinically benign disease. N Engl J Med 1986;315:475-9. 47. Wood GS, Strickler JG, Abel EA, Deneau DG, Warnke RA. Immunohistology of pityriasis lichenoides et variliformis acuta and pityriasis lichenoides chronica: evidence for their interrelationship with lymphomatoid papulosis. J AM ACAD DE•MATOL 1987;16:559-70.