1. Introduction

Lymphomas can be generally classified into Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphomas (NHL), and either B-cell or T-cell lymphoma, based on their cellular origin. Virtually all systems can be involved including nodal and extranodal sites. However, in HL, at onset, nodal and splenic involvement is more common, while extranodal manifestation is more commonly seen in NHL ^[1]. The incidence of extranodal involvement in NHL has been continuously rising due to many factors including immunosuppression and increased use of chemotherapy ^[2][3]. Historical advances in our understanding of lymphoma behavior and pathogenesis have been restricted largely to BCLs and HL compared with mature T-cell lymphomas (MTCLs). The cellular origin of MTCL is complex and not fully understood. T cells emerge from the bone marrow and experience maturation within the thymus by undergoing T-cell-receptor (TCR) gene rearrangement. Diversity of MTCLs is attributed to different types of T cells, each secreting different sets of cytokines signaling other cascades of immune cells. T cells include T-helper (Th) cells, suppressor T cells, cytotoxic cells, memory cells, γδ T cells and natural killer (NK) cells, which is considered a subtype of T cell ^[4]. The most recent WHO 2016 classification of lymphoid tumors now recognizes 29 discrete types of MTCLs. According to the initial site of involvement, MTCLs can clinically be broadly classified into one of four categories, including (1) leukemic disease; (2) nodal disease; (3) extranodal disease; and (4) cutaneous disease. The most common MTCLs subtypes include PTCL, not otherwise specified (NOS) and angioimmunoblastic T-cell lymphoma (AITL), other subtypes include hepatosplenic gamma delta T-cell lymphoma (HSTCL), anaplastic large-cell lymphoma (ALCL), and subcutaneous panniculitis-like T-cell lymphoma (SPTCL), the primary T-cell lymphoma of the intestine ^[5]. Generally, cutaneous T-cell lymphoma (CTCL) without distant metastatic disease is associated with a favorable prognosis of a 90% 5-year survival rate. Later in the course of the disease, progression, as manifested by nodal and visceral involvement, can be seen with a markedly decreased 5-year survival to almost 0%. Prognosis of most PTCL subtypes is generally poor ^[6].

Imaging in general, and specifically FDG PET/CT, plays an essential role in the management of lymphomas. The use of FDG-PET/CT can change the tumor staging in almost 30% of cases. FDG-PET/CT can impact management by further subclassifying lymphomas clinically into aggressive or indolent subtypes based on standardized uptake values (SUVs) and heterogeneity of disease ^[7]. Aggressive lymphomas often display higher SUV (>10–13) on the baseline, or focal disease in nodal or extranodal sites, or diffuse disease within extranodal sites such as the spleen, liver, or bone marrow ^[8]. FDG PET/CT can also help with detecting transformation of lymphomas into more aggressive counterparts by detecting an increase in SUVs of lymphomatous masses despite adequate treatment received, directing the physician to change the management and treatment plan. FDG-PET has been shown to be useful in identifying active residual sites of disease by demonstration of persistent metabolic activity with those masses ^[9][10]. In general, both TCLs and BCLs are FDG-avid on PET/CT. Although FDG avidity has been found to correlate with aggressiveness and clinical behavior of BCLs, the relationship between FDG uptake and different TCL subtypes has not been unquestionably settled. TCLs usually have a poorer prognosis compared to BCLs with a 5-year survival rate of less than 20% ^[6].

2. Changes Contained in the Updated 2016 WHO Classification of T-Cell Lymphoid Malignancies

The updated 2016 World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissue ( Table 1 ) ^[11] account for significant changes in our understanding of lymphoma behavior including both B-cell and T-cell lymphomas since 2008, and refines the pathogenesis and molecular biology of different types of lymphoma and lymphoma-like disorders ^[5][12]. Significant advances have occurred in the classification of TCLs, which has prompted revisions in the 2016 updated WHO classification ( Table 2 ). TCLs can be broadly divided into peripheral (PTCL) and cutaneous types (CTCL). Compared to BCLs, TCLs are relatively rare neoplasms ranging from indolent to aggressive lymphomas. TCLs account for less than 1% and nearly 12% of all lymphomas and NHL cases, respectively ^[13]. Compared to BCL, TCLs have a more aggressive clinical course and are more challenging to diagnose and treat given their rarity.

3. Uncommon Mature T-Cell Lymphoma Variants

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare form of MTCL originating from mature cytotoxic cells. The first case was reported by Gonzalez et al., in 1991 ^[14]. Distinction from the more aggressive primary cutaneous gamma delta TCL was made in the updated WHO classification ^[5].

The two described histopathological aspects of Breast implant associated anaplastic large cell lymphoma include in situ BIA-ALCL (confined to implant capsule), mostly presenting with delayed implant effusion. The second form is infiltrative BIA-ALCL (infiltrating the capsule) mostly related to mass-forming lesions years after surgery ^[15]. Both clinicopathologic forms may coexist in the same patient. In case of late peri-implant seroma, aspiration of at least 50 mL must be performed and sent for culture, cytology and flow cytometry. Fine needle aspiration cytology samples play an important role, and cell block is also crucial as they provide the basis for immunohistochemistry to evaluate for BIA-ALCL versus other entities such as infections/scar/granuloma formation. In cases of mass-forming lesions, core needle should be the preferential approach, and cores should be submitted in saline for flow cytometry if BIA-ALCL is a diagnostic consideration ^[16]. Morphology of cells shows large, atypical lymphoid cells with inflammatory background and eccentric, kidney-shaped nuclei, with homogeneous eosinophilic cytoplasm “hallmark cells” ^[17]. Cells express CD30 and frequent markers for cytotoxic T-cells. The precise pathogenic mechanisms of this type of lymphoma are still to be established. Chronic bacterial antigen stimulation or chronic irritation from implant characteristics may play a role in tumorigenesis ^[18].

Hepatosplenic gamma delta T-cell lymphoma (HTSL) is a very rare, lethal subtype of TCL-NHL, accounting for less than 1% of NHL ^[19]. Although the pathogenesis of HSTL is not completely understood, up to 20% of cases of are seen in long-term immunosuppressed patients, most often post-organ transplantation and in patients receiving immunosuppressive agents for autoimmune disorders such as Crohn disease and rheumatoid arthritis ^[20]. The origin of HSTL in most instances has been hypothesized to be related to immature cytotoxic γδ T cells residing in the spleen. The exact function of this cell is still unclear; however, it is believed to act as the hinge between both the innate and adaptive immune system. It is hypothesized that the pathophysiology of HTSL arises from upregulation of those cytotoxic γδ T cells via the JAK/STAT pathway, induced by various immunomodulator therapies such as azathioprine and monoclonal antibodies that inhibit TNF-α inhibitors (such as infliximab) ^[21][22]. Histologically, the malignant lymphocytes show a spectrum of features, such as cytoplasm devoid of azurophilic granules, nuclei with condensed chromatin and inconspicuous nucleoli, high nucleus-to-cytoplasm ratio, and fine chromatin. HSTL cells can often resemble lymphoblasts encountered in acute leukemia. Malignant lymphocytes initially involve and infiltrate the sinusoids and cords of the red pulp of the spleen. Uncontrolled proliferation within the red pulp causes atrophy of the white pulp.

Most lymphomas affecting the gastrointestinal (GI) tract are B-cell in origin, such as diffuse large B-cell lymphoma (DLBCL), mantle cell, marginal zone, and follicular lymphomas. TCLs of the GI tract are exceedingly rare. A unique subtype of the latter is known as enteropathy-associated T-cell lymphoma, which primarily involves the proximal jejunum and ileum, and represents a diagnostic challenge.

4. Conclusions

The updated fourth edition WHO classification of lymphoid malignancies released in 2016 contains important information for both radiologists and oncologists. Certain rare lymphomas may be occasionally encountered in clinical practice. Although some of those disorders have distinct clinical and imaging features, many overlap with more common disorders, thus causing delay in diagnosis and management. However, early diagnosis of many of these disorders is key as many of these are potentially treatable and early intervention may be lifesaving.

This entry is adapted from the peer-reviewed paper 10.3390/cancers13205217