Lymphomatoid papulosis an ultrastructural study of 2 cases

Summary An ultrastructural study of 2 cases of lymphomatoïd papulosis (Macaulay) showed the prevalence of lymphocytes in the dermal infiltrate, with a variable admixture of other inflammatory cells. These lymphocytes are normal or in lymphoblastic transformation; some are abnormal in size (up to 12 µm in diameter) and have corrugated or cerebriform nuclei like small Sezary cells. Histiocytes have an indented nucleus, an actively phagocytic cytoplasm and sometimes vermiforme inclusions 150–180 Å wide. Circulating and dermal polymorphonuclear leukocytes are rich in caryoschisis. In short, the ultrastructural pattern is inflammatory and also close to lymphomas.

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Zusammenfassung In einer ultrastructurellen Untersuchung von zwei Patienten mit lymphomatoider Papulosis (Macaulay) zeigte sich ein vorwiegend lymphocytäres dermales Infiltrat, das von einer wechselnden Zahl weiterer Entzündungszellen durchsetzt war. Die Lymphocyten erschienen normal oder lymphoblastisch transformiert. Einige Lymphocyten lagen abnorm groß (bis zu 12 µm im Durchmesser) vor und zeigten einen gefalteten oder cerebriformen Nucleus ähnlich kleinen Sezary-Zellen. In den Histiocyten war der Kern eingebuchtet, das Cytoplasma war aktiv phagocytierend mit gelegentlichen vermiformen Einschlüssen (150–180 Å in der Weite). Zirkulierende wie auch dermale Granulocyten zeigten bemerkenswerte Caryoschisis. Das ultrastrukturelle Gesamtbild entspricht dem eines entzündlichen Prozesses mit Verwandtschaft zur Retikulose.

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Presented at the meeting of the Société Française de Dermatologie, Paris, December 13th 1973. Request reprints from Dr. Agache Pierre, Clinique Dermatologique Universitaire. Centre Hospitalier 25030 Besançon — France.     

Lymphomatoid papulosis. Histologic and immunohistochemical studies in a patient with a scaly pigmented eruption

A patient with lymphomatoid papulosis type A showed a peculiar, scaly pigmented eruption on the broad skin areas as well as papulonodular lesions. Large atypical cells characteristic of the infiltrate of the disease were observed not only in the dermal infiltrate of papular lesions, but also in the perivascular infiltrate of the scaly pigmented lesions, indicating that the latter was one of the skin manifestations of lymphomatoid papulosis. Immunohistochemical studies showed that these atypical cells expressed Ki-1 and cellular activation-associated antigens such as HLA-DR, Tac, and T9, but were not reactive with T-cell specific antibodies Leu-1, Leu-3a, and Leu-2a.     

Immunological, cytochemical and ultrastructural studies in lymphomatoid papulosis

In lymphomatoid papulosis two histological types can be distinguished, i.e. type A and type B. In the present study various immunological, enzyme-histochemical and ultrastructural techniques were used to investigate the cellular infiltrate in both types of lymphomatoid papulosis. The type A lesions showed a predominance of large atypical cells, relatively few T cells and few or no Langerhans or related cells, as defined by a positive staining for OKT6 and NA I/34 antisera. The immunological, cytochemical and ultrastructural characteristics of these large atypical cells resembled those of the Langerhans cell/interdigitating reticulum cell series. The morphology and marker profile of these large cells resembled those of Reed-Sternberg cells, which suggests a relationship between lymphomatoid papulosis type A and Hodgkin's disease. The type B lesions showed a predominance of small, medium-sized and large cerebriform mononuclear cells with the phenotype of activated T helper cells, and numerous Langerhans and/or related cells. Their cellular composition was similar to that observed in the early stages of mycosis fungoides.     

Lymphomatoid papulosis: an update and review

Lymphomatoid papulosis (LyP) is a benign chronic often relapsing skin condition that belongs to the CD30-positive cutaneous lymphoproliferative disorders. LyP typically presents as crops of lesions with a tendency to self-resolve, and morphology can range from solitary to agminated or diffuse papules and plaques to nodules or tumours. The clinical–histological spectrum can range from borderline cases to overlap with primary cutaneous anaplastic cell lymphoma (pcALCL). Histology and immunophenotype commonly show overlap with other CD30-positive disorders and sometimes may be identical to pcALCL, making its diagnosis more difficult. Patients with LyP have an increased risk of developing a second neoplasm such as mycosis fungoides, pcALCL and/or Hodgkin lymphoma. Clinical correlation allows its proper classification and diagnosis, which is fundamental for treatment and prognosis. This review focuses on the clinical appearance, histopathological features, diagnosis, differential diagnosis and management of LyP.     

Lymphomatoid papulosis and FK 506

A 53-year-old woman underwent an orthotopic liver transplant in Pittsburgh in October 1990. She had been suffering from chronic hepatitis C that had evolved into cirrhosis with ascites, jaundice, and encephalopathy. In April 1991 she required reconstruction of the biliary anastomosis because of stricture, and in October 1991 she underwent a liver biopsy because of mild elevation of alkaline phosphatase. The biopsy revealed mild chronic rejection and changes consistent with viral hepatitis. She was on oral FK 506, 4 mg b.i.d. In November 1992 she developed recurrent self-healing erythematous, papulonodular lesions on the chest and shoulders (Pig. 1). The lesions were purplish red, mildly pruritic, and undergoing vesiculation on the top. The lesions ranged from 3 to 5 mm in size, and a few showed ulceration and necrosis and were healing with hypopigmented scars. The lesions gradually increased in number and size. A trephine biopsy specimen was obtained from the lesional skin. The tissue was prepared for light microscopic study by fixing in 10% formaldehyde solution and staining with hematoxylin and eosin. Immunohistochemistry was carried out for lymphoid markers. In February 1993, a papulonodular lesion near the left axilla enlarged to a size of 10 × 10 cm; it was ulcerated and necrotic. A biopsy was taken and sent for histopathology and immunohistochemistry. The patient continued on FK 506, 4 mg b.i.d. Many of the early lesions had become purpuric, eroded, and healed with scarring; however, fresh lesions continued to appear. A decision about modification of the patient's immunosuppressive medication was left to the Transplant Team; however, there was concern that her lymphomatoid papulosis may be a side-effect of her PK 506 treatment. Laboratory investigation revealed a normal peripheral blood film. Liver enzymes and a renal profile were within normal limits. The results of a bone marrow study, liver and spleen scan, and endoscopic examination of the gastrointestinal tract were normal. A skin biopsy revealed a nodular and wedge-shaped dermal infiltrate involving the entire dermis. The pleomorphic epidermotropic infiltrate in the upper one-third of the dermis was composed of many round or oval cells with hyperchromatic nuclei. A few nuclei were indented or kidney shaped. Mild mitotic activity was seen. The larger immunoblast-like cells were mixed with normal lymphoctyes and histiocytes. The capillaries had thickened walls with prominent endothelial cells. The second biopsy from the ulcerated axillary lesion showed a dense superficial and deep wedge-shaped infiltrate, abnormal pleomorphic cells, and a few large lymphoid cells (Fig. 2) infiltrating the dermis and extending to the subcutaneous tissue. There were scanty histiocytes, neutrophils, and a few eosinophils. Some of the large abnormal cells had kidney shaped nuclei but most had irregularly shaped nuclei with abundant cytoplasm (Fig. 3). There were many abnormal mitoses, and there were also numerous extravasated red blood cells and edema in the dermis. The epidermis was necrotic and ulcerated. The results of immunohistochemical tests showed a strong reaction for LCA and CD8, but a negative reaction for CD20. The patient's general condition and laboratory tests of hepatic and renal functions remained normal. The results of all hematologic studies, including bone marrow smear, lymph node biopsy, and liver-spleen scan, were normal. The patient continued on FK 506, 4 mg b.i.d. Serum levels of FK 506 which were never communicated to us were sent for the first time in May 1993 and showed a serum level of 39 ng/mL (normal 0.5–2 ng/mL)¹ with an instruction to repeat the test. The dose of FK 506 was immediately reduced to 4 mg/day. The patient revisited the clinic for routine check-up on June 26, 1993. The axillary lesion had disappeared leaving a hyperpigmented scar, the small lesions of lymphatoid papulosis continued to come and go.     

Lymphomatoid papulosis: a follow-up study

A follow-up study has been performed on 16 patients with lymphomatoid papulosis diagnosed at the Finsen Institute during the years 1970-81. In none of the patients did malignant lymphoma develop during the observation period (7 months to 22 years). During this period the nature of the lesions and the tendency to recurrence were unchanged in 11 patients, spontaneous remission took place in 4, and 1 patient went into complete remission after PUVA treatment (8-methoxsalen followed by UVA). The histological material (32 punch biopsies) could be divided into two major groups diagnosed as either typical (16 biopsies) or consistent with lymphomatoid papulosis (16 biopsies). Based on our present knowledge, we suggest the following classification of lymphomatoid papulosis: 1) "classical" lymphomatoid papulosis, 2) lymphomatoid papulosis associated with parapsoriasis en plaque or mycosis fungoides and 3) primary cutaneous T-cell lymphoma.     

Lymphomatoid papulosis with folliculotropism,eccrinotropism and neurotropism

The histopathological characteristics of lymphomatoid papulosis (LyP) vary. Currently, 6 subtypes have been reported, including a new subtype with perifollicular infiltration and different degrees of folliculotropism of CD30+ atypical lymphocytes, known as follicular LyP. However, LyP pathologically manifesting with folliculotropism, eccrinotropism and neurotropism has been rarely reported. We present a case of LyP showing CD30+ atypical lymphocytes around the hair follicle, eccrine gland and nerve fiber, with varying degrees of infiltrates. The pathological characteristics of folliculotropism and eccrinotropism are often associated with mycosis fungoides (MF). This case suggests that differential diagnosis is necessary when atypical lymphocytes infiltrate the follicle and eccrine gland. As folliculotropism and eccrinotropism can occur in both MF and LyP, it may represent a conceptual intersection between the 2 disease processes.     

C型淋巴瘤样丘疹病

报告1例C型淋巴瘤样丘疹病.患者男,52岁.躯干、手腕出现丘疹及溃疡2年,反复发作,并能自愈.皮损组织病理检查:真皮全层有结节或弥漫单一异形大细胞浸润,间有少量嗜酸性粒细胞.免疫组化染色结果显示肿瘤细胞CD3、CD4、CD5、CIM5RO、CD30阳性,CD19、CD79a、CD68、CD15阴性.根据患者临床表现、组织病理检查结果和免疫表型,诊断为C型淋巴瘤样丘疹病.     

Lymphomatoid papulosis: a cutaneous T-cell pseudolymphoma

It was the purpose of this study to further define the nature of the dermal infiltrates in lymphomatoid papulosis (LP) means of enzyme cytochemistry (acid phosphatase and esterase), immunology (rosetting techniques, immunoperoxidase technique on cryostat sections), and by semithin and ultrathin sections. The studies performed on biopsy samples with clinically and histologically typical LP indicated that most lymphoid cells display markers for T-lymphocytes, which were helper T-cells in the one case studied with monoclonal antibodies. Regarding the typical benign self-involutive clinical course, LP is considered to be a cutaneous pseudolymphoma of T-cell type.     

Lymphomatoid papulosis type A: clinical, morphologic, and immunophenotypic study

Background Lymphomatoid papulosis (LyP) is a cutaneous clonal or polyclonal Ki-1 + T-cell lymphoproliferative disorder, morphologically resembling Ki-1 + anaplastic large cell lymphomas (Ki-1 + ALCL) or Hodgkin's disease (HD). Lymphomatoid papulosis usually has a characteristic benign clinical course with remissions and relapses of the cutaneous eruptions. Methods The authors studied three patients with LyP. in each case the diagnosis was established based on the typical clinical history and presentation of the cutaneous lesions as well as the morphologic and immunophenotypic findings. Results in all three cases the skin biopsies showed a polymorphic, nonepidermotropic, dermal lymphocytic infiltrate, composed of small lymphocytes and fewer large, atypical cells. The large ceils were positive for the activation markers CD30 (Ki-1) and CD45R (leukocyte common antigen), and were negative for the HD marker CD15 (Leu Ml). Conclusions In most cases, LyP can be distinguished from Ki-1 + ALCL and HD on the basis of clinical, morphologic, and/or immunophenotypic findings. We emphasize the importance of the recognition of LyP as a clinicopathologic entity and the awareness of dermatologists, oncoiogists, and surgical pathologists in differentiating LyP from other primary cutaneous Ki-1 + lymphoproliferative disorders (Ki-1 + ALCL and HD). The prognosis of cutaneous Ki-1 + ALCL and HD is usually different from LyP and requires a different therapeutic approach.     

Lymphomatoid papulosis associated with mycosis fungoides: clinicopathological and molecular studies of 12 cases

The association of mycosis fungoides and a primary cutaneous CD30+ lymphoproliferative disorder has been reported and probably represents different clinical aspects of a unique T-cell monoclonal expansion. In this study, 12 patients (6 men and 6 women) presented with lymphomatoid papulosis and mycosis fungoides. A TCRgamma gene rearrangement study was performed by an automated high-resolution PCR fragment analysis method on skin biopsy specimens taken from the different clinical lesions in each patient. An indolent clinical course was observed in the majority of patients. T-cell clonality was identified in 7 of 12 lymphomatoid papulosis lesions (58%) and in 6 skin biopsies of plaque stage mycosis fungoides (50%). In each individual case, where T-cell clonality was detected, both mycosis fungoides and lymphomatoid papulosis specimens exhibited an identical peak pattern by automated high-resolution PCR fragment analysis, confirming a common clonal origin. Only one case showed a clonal TCRgamma rearrangement from the lymphomatoid papulosis lesion, which could not be demonstrated in the mycosis fungoides specimen. The demonstration of an identical clone seems to confirm that both disorders are different clinical manifestations of a unique T-cell monoclonal proliferation. Our results also seem to confirm that the association of mycosis fungoides with a primary cutaneous CD30+ lymphoproliferative disorder usually carries a favourable prognosis.     

Lymphomatoid papulosis: remission following intravenously administered acyclovir

In a 54-year-old male patient suffering from Hodgkin's disease, lymphomatoid papulosis occurred. Complete clearing of the skin lesions was observed immediately after intravenously administered acyclovir. The patient had numerous relapses of his skin eruption with complete responses after each course of intravenously applied acyclovir. This striking therapeutic effect parallels reports of regression of mycosis fungoides and chronic generalized lymphadenopathy after acyclovir application. The mode of action of acyclovir in these disorders is not known. They all are characterized by involvement of the T cell system, and in all these diseases, a virus etiology has been proved or is suggested. Thus, a specific effect of acyclovir on T lymphocytes or selectively on helper T cells is discussed. Alternatively, the virustatic effect of acyclovir could be responsible for the therapeutic success.     

Lymphomatoid papulosis and Hodgkin's disease: Are they related?

Two different characteristic types of lymphomatoid papulosis (type A and type B) can be histologically distinguished, that represent the ends of a spectrum. In the present report, two patients are described. One patient with both lymphomatoid papulosis type A and type B lesions for more than 25 years developed Hodgkin's disease (nodular sclerosing type) in the para-aortic and para-iliac lymph nodes. Histologic examination of the skin lesions in the second patient, who had Hodgkin's disease (nodular sclerosing type) in many supradiaphragmatic lymph nodes, showed the characteristic features of lymphomatoid papulosis type A. These findings, together with the results of recent immunohistochemical investigations showing many similarities between the large atypical cells in lymphomatoid papulosis type A lesions and Reed-Sternberg cells in Hodgkin's disease, support the view that lymphomatoid papulosis type A and Hodgkin's disease are closely related conditions. The results of recent studies indicate a close relationship between lymphomatoid papulosis type B and the early stages of mycosis fungoides. Accordingly, the possible relationship between lymphomatoid papulosis types A and B, mycosis fungoides, and Hodgkin's disease is discussed.     

Lymphomatoid papulosis: a study of 18 cases*

Lymphomatoid papulosis (LyP) is a cutaneous eruption that is clinically benign but histologically malignant. To date, more than 300 cases have been published. About 10–20% of the patients develop a lymphoma. The purpose of this study was to make a clinicopathological study of 18 patients diagnosed with LyP in our hospital from 1973 to 1990, to characterize cellular infiltrates in the lesions, to find clonal populations of T-cells and to look for predictive factors of malignant lymphoma in LyP patients. Mean age was 48.7 years. The most frequent clinical lesions were papules (88.8%) followed by plaques (38.8%). The localizations were on extremities (100%), trunk (88%), face (22%), palms or soles (11%), perigenital (11%) and scalp (5%). Two patients have been free of disease for more than 5 years. IgA levels are increased in LyP patients. Neither HTLV I nor III can be considered as a cause of the LyP in any of our patients. Associated diseases were found in 6 cases (1 mycosis fungoides, 1 Hodgkin's disease, 2 anaplastic large-cell lymphoma and 2 large plaque parapsoriasis). Some types of parapsoriasis should be included in the ‘spectrum of Ki-1 lymphomas’. 52 skin biopsies were studied. 17% were type A of Willemze, 67% were type B and 15% were transitional. In 12 of the samples follicular or perifollicular infiltration was found. Follicular LyP should not be considered as a distinct type of LyP. Vasculitis is an uncommon finding in LyP. In all the cases studied, large atypical cells were CD30 +; 5/7 cases had lost CD5 and 4/5 cases had lost CD7. In one case, all T-cell antigens were negative. Cerebriform mononuclear cells were always recognized by T-cell antibodies and they were CD30 positive in only two cases. In one case there were more CD8 + than CD4 + cells. In 5 patients skin and blood samples for genetic rearrangement (beta-T) were taken. Only germinal line was found. We did not find any significant difference between those cases in which malignant lymphoma developed and those in which it did not.     

Lymphomatoid papulosis subtype C: A case report and literature review

Lymphomatoid papulosis (LyP) is a rare CD30⁺ lymphoproliferative primary skin disease with a benign clinical course and malignant histopathology. LyP is classified into seven subtypes based on histopathology: subtypes A through F and LyP with 6p25.3 chromosome rearrangement. We present here, a case report of a 51‐year‐old man, afflicted with multiple papules and nodules on his left arm for over 3 months and diagnosed with LyP subtype C. The patient refused treatment, and his lesions faded with no visible rash on the left arm 14 months after diagnosis.