Research Progress in Classification and Treatment Lymphomatoid Pap-ulosis

Lymphomatoid pap-ulosis (Ly P) is a relatively common low-grade malignant cutaneous lymphoma, which is a skin CD30-positive lymphoproliferative disease associated with primary anaplastic large cell lymphoma. Ly P clinical manifestations of chronic recurrent, self-healing papules, nodules, pathological manifestations of epidermal or dermal metaplasia of lymphocytes, tumor cells express CD30 markers. The disease was first named by Ma-caulay in 1968, but its origins were not known at the time. In 1972, Black et al. found abundant hydrolase in atypical large cells of Ly P, which was mistaken for the origin of tissue cells. In 1981, Weinman et al. and Brehmer-Andersson proposed that Ly P is the origin of lymphocytes. In 1986, Weiss et al. confirmed the monoclonal properties of T cells in Ly P by TCR gene rearrangement detection. In the same year, Kaudewitz et al. confirmed the expression of CD30 in tumor cells in Ly P by immunohistochemistry. This article briefly introduces the basic classification of Ly P and the special clinical, pathological and immunohistochemical types, points out the current problems in diagnosis, and briefly introduces the treatment of lymphoma-like papulosis.

1. Basic classification of Ly P

1.1 Type A and B

In 1982, Willemz et al. divided Ly P into type A and type B. Type A is the most common histopathological type characterized by scattered or clustered atypical large cells mixed with small lymphocytes, neutrophils, and eosinophils to form wedge infiltration. Since tumor cells are similar in morphology to tissue cells, they are also referred to as tissue cell types in the past literature. Type B is a rare type characterized by a wedge-shaped infiltration of CD4-positive small to medium-sized polymorphic cells in the dermis, or a banded pro-epithelial infiltration with tumor-like morphologically similar sputum-like granuloma.

1.2 Type C

In 1993, Willemze et al. first demonstrated clinically necrotizing papules and nodules, but the pathological manifestations of anaplastic large cell lymphoma were defined as the new Ly P subtype. Its clinical features are consistent with the classic lymphoma-like papulosis, but the pathological manifestations are intradermal flaky atypical large cell infiltration, similar to cutaneous anaplastic large cell lymphoma.

1.3 Type D

In 2010, Saggini et al reported 9 patients whose clinical features were consistent with Ly P and were inert biological behavior. However, the pathological manifestations were obvious CD8+ lymphocyte infiltration of the epithelial cells. The cells were small to medium-sized lymphocytes, which were similar to the pathologically invasive epithelial CD8-positive cytotoxic lymphoma of the primary skin, but the tumor cells expressed CD30 markers to varying degrees. Domestic cases such as Xiong Jingshu and Wen Pengfei reported similar cases. In 2012, Kempf et al reported 13 similar patients, but the authors diagnosed it as P30, which expresses CD30, Pityriasis lichenoid et al vari-oliformis acuta (PLEVA). Recent studies have found that about one-third of children with Ly P have had PLEVA or chronic lichen-like pityria before onset. Infiltration of CD30+ cells has been reported in lesions of more than 15 children with lichen-like pityriasis, and studies have found that monoclonal T cells can be detected in some PLEVA. These findings suggest that there is no absolute distinction between D-type Ly P and PLEVA, which may be lineage diseases.

1.4 Type E

In 2012, Kempf et al first reported 16 patients with type E Ly P. The clinical manifestations were single or scattered in a few papules, rapidly progressing to larger ulcers, and hemorrhagic necrosis and eschar-like appearance. 4cm. The pathological manifestations are the vascular infiltration of pleomorphic lymphocytes. In some patients, vascular destruction can be observed and intravascular thrombosis can occur.

1.5 Type F

Type F is pro-hair follicular Ly P. In 1980, Pierard et al first reported two cases of papules and nodules intermittently around the hair follicle or ruptured hair follicles. Pathologically, the atypical lymphocytes and inflammatory cells infiltrated in the superficial dermis around the hair follicle, and the multinuclear Reed-Sternberg was seen. Like cells. Kempf et al. summarized the characteristics of pro-follicular Ly P as follows: CD30+ cell infiltration in the hair follicle and around the hair follicle, wall expansion, hair follicle rupture, hair follicle epithelial hyperplasia, and neutrophil aggregation in the hair follicle epithelium. However, some studies have found that pro-hair follicles can be observed in all types of Ly P. Therefore, whether the pro-hair follicular Ly P is an independent subtype is still worth discussing.

1.6 6p25.3 chromosomal rearrangement

In 2013, Karai et al first reported 11 cases of Ly P that showed histologically biphasic growth pattern. These cases have two different types of tumor cells. The superficial tumor cells are cerebral regurgitation small lymphocytes, which have pro-epidermal properties, and form Pepti-like reticulocyte hyperplasia in the epidermis. The deep cells are cells. Larger anaplastic lymphocytes with flaky and nodular hyperplasia. Tumor cells express CD30, in which superficial small tumor cells are less stained than deep large tumor cells. The unique molecular biology of this type of case is the rearrangement of DUSP22-IRF4 gene on chromosome 6p25.3 in tumor cells. Some scholars believe that the rearrangement of 6p25.3 leads to a decrease in the expression of DUSP22, which weakens the tumor suppressive effect and may play a tumor-inducing role.

2. Special type of Ly P

2.1 Clinical special type

Ly P can manifest as a patchy change, an aneurysm-like change, or a similar acne-like vesicular-like change in rare cases. Some patients with rash can occur in special anatomical parts, such as eyelids. There are also a few cases where the rash can be confined to a certain area of the body, and even the patient’s rash is confined to Becker’s or appears on the basis of a tattoo.

2.2 Pathological special type

In 2003, Crowson et al first reported 9 cases of pro-sweat gland type Ly P, and there was a cell infiltration based on sweat glands, which showed two modes: one mode was mainly small lymphocytes, mixed with a small amount of large cell infiltration; another It is a pleomorphic cell infiltration with granulomas. Ly P may have reactive epidermal hyperplasia, which has been reported in previous literature as keratoacanthoma, and similar cases have been reported in primary cutaneous anaplastic large cell lymphoma. This so-called keratoacanthoma-like alteration may represent a reactive hyperplasia of the epidermis that occurs on the basis of lymphoma, rather than a true keratoacanthoma.

2.3 Immunohistochemical special phenotype

Ly P can express CD56 markers, but the expression of CD56 is not associated with prognosis. Recently, it has been reported that Ly P can exhibit γδT phenotype, and Ly P of γδT phenotype has no obvious invasive clinical behavior. A small number of cases report CD30-negative Ly P, including the recently reported CD30-negative D-type Ly P. Cerroni believes that CD30 negative may be the cause of laboratory techniques, but other investigators believe that there are true CD30-negative cases.

3. Relationship between Ly P and other malignant lymphomas

Approximately 10% to 20% of patients with Ly P have associated malignant lymphoma, and in a recent large-scale retrospective study, the incidence of associated lymphoma reached 52%. Some studies have found that positive TCR gene rearrangement is associated with the occurrence of lymphoma, and the incidence of related lymphoma is a continuous process. With the prolongation of time, its incidence gradually increases and remains stable after 18 years. . In the long follow-up study, the incidence of associated lymphoma was higher than those with shorter follow-up. According to previous literature, the incidence of mycosis fungoides and primary cutaneous anaplastic large cell lymphoma is highest in Ly P patients, and its genetic association with Ly P has been confirmed by several studies.

4. Progress in the treatment of Ly P

Ly P is an inert disease with self-healing characteristics, and treatment is usually used to control the spread of rash and reduce the frequency of recurrence. There is currently no evidence that any existing treatment regimen can reduce the frequency and number of relapses or prevent the onset of associated lymphoma, and that lesions usually recur after treatment interruption.

4.1 Topical medication

The commonly used topical drug is glucocorticoid, which can be used as a first-line treatment for patients who are seeking rapid symptom relief, but glucocorticoids do not achieve complete remission in most cases. Recently, researchers have achieved better therapeutic effects through topical methotrexate (MTX). Other topical drugs used for treatment include: nitrogen mustard, imiquimod, retinoic acid and the like.

4.2 Phototherapy

Ultraviolet treatment can induce lymphocyte apoptosis with relatively few side effects and can also be used for the treatment of Ly P. Some researchers have tried to treat with PUVA, UVA1 and 308 nm excimer lasers, and have succeeded in most patients.

4.3 Systemic treatment

MTX is often used as the preferred systemic treatment for Ly P. In a retrospective study of 40 patients with Ly P, MTX 15-25 mg was given subcutaneously for 1 week, 44% had no new lesions, and 42% had only a small amount of new lesions. After stopping treatment, 25% of patients did not relapse during the 24-227 month follow-up period. However, most patients experienced varying degrees of side effects, and 5 of 10 patients who had been treated with MTX for more than 3 years had liver fibrosis. The study found that IFN-α has a long-term and long-lasting effect on Ly P, which may be related to the induction of high-efficiency Th1 type immune response and promotion of CD95 expression of apoptotic receptor. In an open trial, 3-15 MU IFN-α was administered weekly, and after 2-6 weeks, 4 of 5 patients achieved complete remission. It will recur within 3-4 weeks after stopping treatment, so it is necessary to maintain treatment for 10-17 months. The latest experimental data indicate that the combination of MTX and IFN-α is effective in the treatment of Ly P. In a clinical phase 2 study using Brentuximabvedotin (CD30 monoclonal antibody binding agent c AC10-vc MMAE) 1.8 mg/Kg 21 days/intravenous injection, all Ly P were therapeutically effective, the main adverse reaction being peripheral sensory neuropathy. From the clinical situation, CD30 monoclonal antibody is expensive and has certain side effects, so there is still a certain distance from clinical large-scale application.

5. Conclusion of Ly P

Ly P is a low-grade malignant tumor. The diagnosis needs to be closely combined with clinical and pathological. CD30 staining has diagnostic value. There are still some clinical problems in Ly P research that deserve further study, such as whether Ly P and PLEVA are lineage diseases, whether pro-follicular Ly P is a specific subtype, Ly P and mycosis fungoides, and other types of lymphoma. Relationships, etc.