Primary cutaneous B-cell lymphomas (PC-BCL) are a group of extranodal B-cell non-Hodgkin lymphomas that originate in and are usually confined to the skin at diagnosis [1,4]. They account for approximately 29% of all primary cutaneous lymphomas and comprise three main subtypes: primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous marginal zone lymphoma (PCMZL), and primary cutaneous diffuse large B-cell lymphoma, leg type (PC-DLBCL, leg type) [1,5]. PCFCL is the most common subtype (57% of PC-BCL), located primarily on the scalp, face, forehead, and trunk, typically presenting as solitary, firm, pink to violaceous papules, nodules, plaques, or tumors; ulceration is rare and multifocal lesions occur in about 15% of cases [1,2]. It follows an indolent course with a 5-year overall survival (OS) rate exceeding 95% [1,2]. PCMZL (also termed primary cutaneous marginal zone lymphoproliferative disorder in the International Consensus Classification) is the second most common subtype (24%–31% of PC-BCL), with distribution primarily on the trunk, upper extremities, and head; it presents as solitary or multiple erythematous to violaceous papules, small nodules, plaques, or tumors and has an excellent prognosis with a 5-year survival rate of 99% [1]. The rarest subtype is PC-DLBCL, leg type (11%–19% of PC-BCL, 4% of all primary cutaneous lymphomas), which is distributed mostly to the leg but can occur at other sites in 10%–15% of cases; it typically appears as red to bluish plaques or tumors that can ulcerate and is aggressive with a poor prognosis (5-year OS rate of 50%) due to frequent extracutaneous relapses [1,2,3].

Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma (CTCL), and many clinicopathologic variants have been described [1,2]. MF is characterized by malignant transformation of skin-resident effector memory T cells and typically exhibits an indolent clinical course with intermittent, stable, or slow progression of skin lesions. Extracutaneous involvement may be seen in advanced stages, including lymph nodes (LNs), blood, or less commonly other organs [1,2]. Sézary syndrome (SS) is the leukemic variant of CTCL, closely related to MF but with unique characteristics. SS is rare, accounting for less than 5% of cutaneous lymphomas, and predominantly affects older individuals [1-3]. SS is characterized by the presence of atypical T cells (Sézary cells) in the skin causing diffuse erythema (erythroderma) and significant blood involvement with more than 1,000 abnormal cells/µL, defined as Sézary cells by cytopathologic assessment or flow cytometry (abnormal subsets including but not limited to CD4+CD7- or CD4+CD26- cells); TRBC1 may contribute in detecting clonality and can improve specificity when CD7 and CD26 are lost [3]. SS is thought to arise from thymic memory T cells, while MF arises from skin-resident effector memory T cells, supporting the contention that SS is a process distinct from MF [4]. Cases presenting as an overlap of these two conditions exist. The diagnostic workup includes biopsy of suspicious skin sites with immunohistochemistry (CD2, CD3, CD4, CD5, CD7, CD8, CD20, CD30) and molecular analysis to detect clonal TRB and TRG gene rearrangements [5]. Large-cell transformation (LCT) of MF is defined histologically as more than 25% of tumor cells displaying large size; CD30 expression may be seen but is not part of the definition of LCT [6].

Primary cutaneous CD30+ T-cell lymphoproliferative disorders (PCTLD) represent a spectrum that includes primary cutaneous anaplastic large cell lymphoma (PC-ALCL), lymphomatoid papulosis (LyP), and 'borderline' cases with overlapping clinical and histopathologic features [1-3]. Clinical correlation with histopathologic features is essential for diagnosis; it cannot be made based on pathology alone. It is critical to distinguish these from other processes expressing CD30, including systemic T-cell lymphomas (e.g., systemic ALCL, adult T-cell leukemia/lymphoma [ATLL], PTCL), other CD30+ cutaneous lymphomas such as MF with large-cell transformation (MF-LCT), and benign disorders such as lymphomatoid drug reactions, arthropod bites, and viral infections [1,2]. Lymphomatoid drug reactions have been linked with certain drugs (e.g., amlodipine, carbamazepine, cefuroxime, valsartan) and may show CD30+ atypical large cells histologically. MF and primary cutaneous CD30+ T-cell LPD can coexist in the same patient. PC-ALCL represents about 8% of cutaneous lymphoma cases [1]. Unlike systemic ALCL, PC-ALCL typically follows an indolent course; although cutaneous relapses are common, an excellent prognosis is usually maintained [4,5]. Histologically, PC-ALCL shows diffuse, cohesive sheets of large CD30+ (>75%) cells with anaplastic, pleomorphic, or immunoblastic appearance [1]. Clinical features typically include solitary or localized nodules or tumors (often ulcerated); multifocal lesions occur in about 20% of cases. Extracutaneous disease occurs in about 10% of cases, usually involving regional lymph nodes [1]. LyP is included under the WHO-EORTC classification but may be best classified as a lymphoproliferative disorder due to its frequently spontaneously regressing nature [1]. LyP is associated with other lymphomas such as MF, PC-ALCL, systemic ALCL, or Hodgkin lymphoma [6,7]. LyP is histologically heterogeneous with large atypical anaplastic, immunoblastic, or Hodgkin-like cells in a marked inflammatory background [1]. Clinical features are characterized by chronic, recurrent, spontaneously regressing papulonodular (grouped or generalized) skin lesions [1,6].

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a very rare subtype of cutaneous T-cell lymphoma characterized by mature, medium-sized, CD8+ activated T cells with tropism towards adipocytes in the subcutaneous tissue and, in extraordinary cases, involving adipocytes at other sites like the mesentery [SPTCL/INTRO-1]. It accounts for less than 1% of all non-Hodgkin lymphomas, with a 5-year survival average of approximately 80% [4]. Patients with SPTCL tend to be young, often with a personal or family history of systemic lupus erythematosus (SLE) or other autoimmune disorders [SPTCL/INTRO-1]. The presentation includes non-ulcerated deep nodules typically involving the legs and other sites. The process may resolve with areas of lipodystrophy and hyperpigmentation. Fever and malaise are commonly observed at presentation. Signs and symptoms of hemophagocytic lymphohistiocytosis (HLH) may occasionally lead to severe morbidity or mortality; markers of HLH should be checked when SPTCL is suspected, with ferritin levels as a reliable marker to assess disease evolution [SPTCL/INTRO-1, TCLYM-F]. Rimming of bone marrow adipocytes by CD8+ T cells may be observed, but tumoral growth in nodal, bone marrow, or mesenchymal organs is not typically seen [SPTCL/INTRO-1]. This limited growth potential, along with the lack of common lymphoma driver mutations and the frequent detection of germline mutations in the HAVCR2 gene, suggests an immune dysregulation characterized by unchecked activated T cells driving the process [SPTCL/INTRO-1]. HAVCR2 encodes for T-cell immunoglobulin and mucin domain protein 3 (TIM-3), a membrane modulator of immune response resulting in hemophagocytosis and uncontrolled activation of the innate immune system. HAVCR2 mutations appear to be more prevalent in patients of Asian ancestry [SPTCL/INTRO-1, 24,31-33].

Primary cutaneous indolent T-cell lymphoproliferative disorders (LPD) were previously classified as primary cutaneous lymphomas but, due to their excellent prognosis and absence of extracutaneous progression, have been re-classified as LPD by both 2022 WHO classification and International Consensus Classification (ICC) [1-4]. They should be distinguished from malignant CTCL. The primary cutaneous indolent LPDs include primary cutaneous CD4+ small/medium T-cell LPD (PCSM-TLPD) [5] and primary cutaneous CD8+ acral T-cell LPD (PCA-TLPD) [6]. PCSM-TLPD typically presents as solitary asymptomatic nodule or plaque on the head and neck, trunk, or upper extremities; spontaneous regression is common. Histology shows superficial band-like or nodular/diffuse infiltrate of predominantly small/medium-sized CD4+ T cells with a T-follicular helper (TFH) phenotype (CD3+, CD4+, CD8-, PD-1+, ICOS+, BCL6-/+, CXCL13-/+) and admixed reactive CD8+ T cells, B cells, plasma cells, and histiocytes [5]. PCA-TLPD presents as solitary asymptomatic papule, nodule, or plaque on ear, nose, or other acral sites; spontaneous regression is less common but can occur. Histology shows dermal, non-epidermotropic, diffuse or nodular infiltrate of atypical medium-sized CD8+ T cells with cytotoxic phenotype (CD3+, CD4-, CD8+, TIA+, granzyme B+/-, dot-like expression of CD68 in tumor cells, TCR alpha/beta) [6]. Both disorders have clonal TRB/TRG gene rearrangements in most cases. The 5-year overall survival rate is 100% for both PCSM-TLPD and PCA-TLPD; relapse is rare for PCSM-TLPD and uncommon for PCA-TLPD [5,6].