All patients underwent FDG PET/CT on one of four PET/CT systems without specific preference (Biograph16, Siemens Healthcare Molecular Imaging; or Discovery LS, Discovery ST, or Discovery STE, all from GE Healthcare). Images were acquired after IV injection of 15 mCi (555 MBq) FDG and a 60- to 90-minute uptake period. Blood glucose level was less than 200 mg/dL before injection. Oral contrast medium (meglumine diatrizoate, Gastrografin, Bristol-Myers Squibb; 2.5% solution, 1,000 mL) was administered. After CT (120 kV, 40–80 mA), PET emission images were obtained at 3 minutes per bed position. Patients with a diagnosis of cutaneous T-cell lymphoma were imaged from the vertex to the feet; otherwise, the image range extended from midskull to upper thighs. PET, CT, and fusion images were reviewed on a workstation integrated with a PACS (Centricity AW Suite version 2, GE Healthcare) that allowed multiplanar reformatting of images. Slight differences in resolution and quantification can be observed between the different PET/CT systems; however, we have observed ≤ 10% differences in maximum SUV provided that all other parameters, such as uptake time and image reconstruction parameters, are standardized.

Maximum SUVs across subtypes were compared using a one-way analysis of variance, and the pairwise p values were adjusted for multiple comparisons using the bootstrap [15]. These data are also summarized in the form a box plot (Fig. 1). A p value of less than 0.05 was considered statistically significant.

Sites of active disease were clearly detected in all histologic subtypes. The fraction of PET-positive patients varied within each histologic subgroup, as well as the intensity of FDG uptake (Fig. 1). The highest SUVs were recorded in patients with aggressive variants, as specified in Figure 1. Of note, there was a significant difference in the mean maximum SUV in patients with mycosis fungoides with transformation (SUV, 11.3) compared with patients with mycosis fungoides without transformation (SUV, 3.82; p < 0.05). In addition, the SUVs were significantly higher in systemic anaplastic large cell lymphoma than in mycosis fungoides, angioimmunoblastic T-cell lymphoma, NK cell–T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, and peripheral T-cell lymphoma, unclassified (p < 0.02). There was no significant difference in maximum SUV between anaplastic large cell lymphoma and human T-cell lymphotropic virus (HTLV)–associated T-cell lymphoma or enteropathy-associated T-cell lymphoma.

Thirty-nine patients (29%) had sites of disease beyond the range of a diagnostic neck, chest, abdomen, and pelvis CT scan. These sites included cutaneous, subcutaneous, and muscular masses of the scalp, upper and lower extremities, and lymphadenopathy in epitrochlear and popliteal regions.

Peripheral T-cell lymphoma, unspecified—The designation of peripheral T-cell lymphoma, unspecified, includes all lymphomas of mature postthymic T-cell origin, without specific clinicopathologic features that permit further classification. Sixty percent of patients have stage IV disease at the time of diagnosis [16]. We encountered 34 patients with this disease, 33 of whom had FDG-avid disease. Eight (24%) of 33 patients had cutaneous or subcutaneous lesions. Twenty-nine patients (88%) showed FDG-avid lymphadenopathy, 17 (51%) had visceral disease, and, in four patients, second primary malignancies were detected incidentally, involving the breast, lung, colon, and epiglottis. The range of maximum SUVs for all sites was 2.8–42.3 (mean, 12.3), indicating the heterogeneous and predominantly FDG-avid nature of this disease.

Anaplastic large cell lymphoma—Primary systemic anaplastic large cell lymphomas may be further classified into two subtypes, anaplastic lymphoma kinase positive and negative. Expression of the anaplastic lymphoma kinase protein confers a more favorable prognosis than the other peripheral T-cell lymphomas [16]. Our population included 16 patients with systemic anaplastic T-cell lymphoma. In four cases (25%), we noticed cutaneous or subcutaneous focal FDG uptake. One patient had multiple subcutaneous nodules along the lymphovascular drainage pathway from the lower extremity (Fig. 2). Increased FDG uptake in lymph nodes was seen in 15 patients (94%), with SUVs between 3.3 and 37.0. Eight (50%) patients had visceral sites of disease, specifically involving lung (n = 3) and muscle, bone, liver, tonsil, and parotid gland (n = 1 each). There was no obvious association between anaplastic lymphoma kinase–positive (n = 4) or anaplastic lymphoma kinase–negative (n = 12) state and the FDG avidity of tumors.

Angioimmunoblastic T-cell lymphoma— Angioimmunoblastic T-cell lymphoma is a distinct subtype of peripheral T-cell lymphoma that manifests clinically with lymphadenopathy, hepatosplenomegaly, skin rash, and constitutional symptoms, with evidence of dysregulation of the immune system. Many patients show hypergammaglobulinemia, Coombs-positive hemolytic anemia, and evidence of immunodeficiency [16]. Our study population included 18 patients with angioimmunoblastic T-cell lymphoma at initial staging or relapse, 14 of whom had FDG-avid disease detected on PET. None of these 14 patients had hypermetabolic skin lesions, but all showed FDG-avid lymphadenopathy (average maximum SUV, 12.3; range, 4.1–29.2). Seven patients had visceral involvement (in some cases at multiple sites), including the spleen (n = 4), bones (n = 2), lung (n = 2), multifocal sites in the gastrointestinal tract (n = 1), liver (n = 1), or nasopharynx (n = 1).

Extranodal NK cell–T-cell lymphoma, nasal type—Extranodal NK cell–T-cell lymphoma, nasal type, is the most common peripheral T-cell lymphoma in Asian populations and has been previously called both angiocentric lymphoma and lethal midline granuloma [5]. Epstein-Barr virus infection may play a role in tumorigenesis. The tumor often involves the nasal cavity or paranasal sinuses, and tumor necrosis is a common feature [17]. Identical tumors can develop in an extranasal location (hence, the designation “nasal type”), including the skin, gastrointestinal tract, testis, kidneys, and respiratory system.

We reviewed PET scans for 12 patients with extranodal NK cell–T-cell lymphoma, 10 of whom had true-positive FDG-avid disease. Only one patient had a primary nasal tumor (Fig. 3). Six patients had predominantly cutaneous disease, varying from a solitary cutaneous lesion to innumerable cutaneous and subcutaneous masses. Visceral involvement was seen in seven cases, involving lung (n = 3), bone marrow (n = 2), spleen (n = 2), and intestine, liver, and pericardium (n = 1). Nodal sites of disease were also seen in six patients.

Enteropathy-associated T-cell lymphoma— Enteropathy-associated T-cell lymphoma is a rare lymphoma that typically occurs in elderly patients with a history of celiac disease or dermatitis herpetiformis. The diagnosis of celiac disease may not have been established before the diagnosis of lymphoma; however, pathologic specimens usually have evidence of villous atrophy in the adjacent nonlymphomatous bowel [4].

Two patients with this rare diagnosis underwent FDG PET/CT. For one patient, the PET/CT scan showed an FDG-avid ileal mass and mesenteric adenopathy. The other patient had already undergone ileal resection, but the postsurgical staging PET/CT scan revealed two FDG-avid small intestinal foci, which had not been seen optimally on either a contrast-enhanced CT or small-bowel follow-up study.

Mycosis fungoides—Mycosis fungoides is a cutaneous T-cell lymphoma attributed to the clonal expansion of epidermotropic CD4⁺ helper T cells that exists in three clinical phases: patches, plaques, and tumors [18]. There were 12 patients with mycosis fungoides in our study; PET/CT detected local cutaneous disease in nine cases, comprising one or more FDG-avid plaques or tumors (Table 1). Patches (n = 2) were only appreciated clinically and were not amenable to radiologic detection. Mycosis fungoides tumors are known to be visible on CT scans [5, 19]; however, we were able to detect abnormal FDG uptake associated with both plaque and tumor disease in nine of 10 cases on PET/CT, when particular attention was devoted to the skin. Cutaneous disease in mycosis fungoides had a spectrum of radiologic appearances that varied from areas of cutaneous soft-tissue thickening to frank exophytic soft-tissue masses (Figs. 4, 5, 6). We found hypermetabolic adenopathy in only four of the 12 patients with plaque or tumor stage disease. No patient showed visceral involvement.

Sézary syndrome—Sézary syndrome is a leukemic variant of mycosis fungoides, in which characteristic Sézary cells are found in the peripheral blood. These cells are the result of a clonal proliferation of malignant T cells; they show a loss of normal cell surface antigens and characteristic hyperconvoluted cerebriform nuclei. Clinically, diffuse erythroderma is seen [18]. Our study population included eight patients with Sézary syndrome. Only two of six clinically erythrodermic patients showed a pattern of diffusely increased cutaneous FDG uptake. This pathologic finding simulates the artifact of diffuse superficial FDG uptake seen in nonattenuation-correction PET emission images (Fig. 7). Three of the eight patients exhibited focal FDG-avid skin lesions (SUV range, 3.4–10.2). FDG-avid lymphadenopathy was seen in all eight patients (SUV range, 3.5–6.2). Low-grade FDG uptake in lymph nodes is of uncertain clinical significance in Sézary syndrome because benign dermatopathic lymphadenitis commonly occurs. This term refers to the reactive enlargement of lymph nodes draining areas of disruption of cutaneous integrity, thus explaining the false-positive FDG uptake on PET. Of our eight patients with Sézary syndrome with FDG-avid lymph nodes, only two had biopsyproven malignant involvement, one had probable malignant lymphadenopathy on the basis of clinical assessment, and five had likely false-positive FDG uptake secondary to dermatopathic lymphadenopathy, on the basis of clinical assessment. One patient had hypermetabolic infiltration of skeletal muscle; otherwise, there was no visceral disease.

Mycosis fungoides with large cell transformation—Mycosis fungoides may undergo transformation to a CD30⁺ anaplastic large cell lymphoma with aggressive biologic behavior in up to 39% of patients [20]. We encountered 11 cases of mycosis fungoides with large cell transformation, and 10 had true-positive FDG PET/CT scans. Nine of these patients had markedly FDG-avid cutaneous lesions (Fig. 8). The average maximum SUV in this group of patients (SUV, 11.3) was significantly higher than that in the group of patients with mycosis fungoides without transformation (SUV, 3.8) and that for patients with mycosis fungoides and Sézary syndrome (SUV, 5.0; p < 0.05). Eight of the 10 patients also had hypermetabolic lymphadenopathy. Visceral involvement was observed frequently, with parotid gland involvement in two patients, diffuse splenic involvement in two patients, and hypermetabolic infiltration of the gracilis muscle in the lower extremity in one patient.

Subcutaneous panniculitis-like T-cell lymphoma—In subcutaneous panniculitis-like T-cell lymphoma, which is a rare distinct primary lymphoma of the subcutaneous tissues, multifocal subcutaneous infiltrates of malignant T lymphocytes are associated with benign histiocytic inflammatory cells. A characteristic histopathologic feature is the rimming of individual fat cells by neoplastic lymphocytes [21]. Clinically, numerous indurated poorly circumscribed firm violaceous cutaneous plaques and nodules develop. Subcutaneous panniculitis-like T-cell lymphoma shows a spectrum of clinical behavior; a more aggressive hemophagocytic syndrome is sometimes seen, manifested by coagulopathy, B symptoms, and hepatosplenomegaly, and it invariably has a fatal outcome [4].

The unique imaging findings of subcutaneous panniculitis-like T-cell lymphoma are not widely described [5, 10]. CT depicts multifocal areas of soft-tissue subcutaneous infiltration with poorly defined margins. In our experience, these lesions range in size from a few centimeters to confluent infiltration of the entire subcutis of the trunk and lower extremities (Figs. 9 and 10). Infiltration of the omental fat was also seen in one patient. The degree of soft-tissue infiltration of the adipose tissue is variable, ranging from negative Hounsfield units, indicating significant residual fat, to average soft-tissue Hounsfield unit values, indicating predominant soft-tissue component. On metabolic imaging, these lesions are invariably FDG avid. All of our nine cases showed multifocal hypermetabolic subcutaneous infiltrative lesions (Table 1). Pulmonary infiltrates were observed in one case, featuring multiple ground-glass nodules between 0.5 and 1.5 cm diameter. Only one of nine patients had a solitary hypermetabolic inguinal lymph node. Subcutaneous panniculitis-like T-cell lymphoma lesions could potentially be misinterpreted as sites of subcutaneous injection if the anterior abdominal wall or gluteal region is involved. The differential diagnosis also includes inflammatory disorders of the subcutaneous tissues, such as erythema nodosum or erythema induratum, as well as inflammatory or infectious panniculitis [5].

Primary cutaneous anaplastic large cell lymphoma—Primary cutaneous anaplastic large cell lymphoma belongs to a spectrum of disease that includes the benign entity lymphomatoid papulosis, and differentiation between these conditions can be challenging for the clinician and the pathologist. Patients usually present with nonregressing cutaneous nodules 1–2 cm in size [4]. In up to 10% of cases, spread to extracutaneous sites may occur [4]. Our study population included four cases of primary cutaneous anaplastic large cell lymphoma. Two cases showed false-positive FDG uptake: one with increased focal tracer activity in the calf (maximum SUV, 2.9) and the other with focal suspicious uptake at the site of a previously irradiated skin lesion (maximum SUV, 3.4); biopsy results were negative for lymphoma. The other two cases were true-positives: One patient showed an area of mild FDG uptake in a skin lesion in the flank (SUV, 2.2). In the other patient, PET/CT demonstrated true-positive FDG-avid disease progression to extracutaneous sites involving the lungs and mediastinal lymph nodes.

Adult T-cell leukemia lymphoma (HTLV associated) is a distinct peripheral T lymphocyte malignancy associated with HTLV type 1, a retrovirus endemic in the Caribbean and Japan [4]. We reviewed FDG PET/CT in nine patients at the time of initial staging or relapse, and all showed sites of FDG-avid disease (Fig. 1). One third of patients had FDG-avid cutaneous and subcutaneous lesions, and eight of nine had FDG-avid lymphadenopathy (Fig. 1). Extranodal disease was observed in six patients, involving the spleen (n = 3); bone (n = 2); and the liver, nasopharynx, nose, lung, and parotid gland (n = 1).