Primary cutaneous acral CD8 positive T cell lymphoproliferative disorder
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| Primary cutaneous acral CD8 positive T cell lymphoproliferative disorder | |
|---|---|
| Other names | Primary cutaneous acral CD8 positive T cell lymphoma, Indolent CD8+ lymphoid proliferation of the ear |
| Specialty | Dermatology, Oncology |
| Symptoms | Cutaneous nodule or plaque |
| Usual onset | Adults usually 29 years of age or older |
| Treatment | Surgery and/or radiotherapy or just observation |
| Prognosis | Good to excellent |
| Frequency | Rare |
Primary cutaneous acral CD8 positive T cell lymphoproliferative disorder (CD8+ TLPD) is one type of the lymphoproliferative disorders, subclass cutaneous T-cell lymphoma, in which a slow-growing nodule or papule develops on the ear or, less commonly, other acral sites. CD8 positive T-cells (i.e., CD8+ T-cells) are a subtype of the lymphocytes and acral sites are peripheral parts of the body, i.e., the hands, arms, feet, legs, ears, nose, fingernails, and toenails.[1] In 2007, Petrella et al.,7[2] reported four patients with tumors composed of CD8+ T-cells and termed the disorder indolent CD8+ lymphoid proliferation of the ear. In 2018, the World Health Organization and European Organisation for Research and Treatment of Cancer provisionally classified this disorder as a lymphoma and termed it primary cutaneous acral CD8 positive T cell lymphoma.[3] (The "primary" used to designate cutaneous lymphomas indicates that the lymphoma was first diagnosed as limited to the skin and there was no evidence of spread to extracutaneous tissues for 6 months after the diagnosis was first made.[4]) In 2022, however, the International Consensus Classification (ICC) group of experts in various medical fields maintained that this disorder was not malignant and therefore termed it primary cutaneous acral CD8 positive T cell lymphoproliferative disorder.[1][5] In 2024, the World Health Organization (WHO) agreed with this classification and designation.[6] However, histiocyte and CD8 T-cell-rich lymphoproliferations of the skin in individuals with primary immunodeficiency (i.e., individuals born with an immunodeficiency due to genetic causes), which had been regarded as a form of CD8+ TLPD, was reclassified as one of the inborn error of immunity-associated lymphoproliferative disorders by the WHO (2022) classification of hematolymphoid tumors.[6][7] That is, it is now designated as a histiocyte and CD8 T-cell rich lymphoproliferative disorder in patients due to their having an inborn error of immunity.[8] Here, these ICC and WHO classifications are followed, i.e., primary cutaneous acral CD8 positive T cell lymphoma is termed primary cutaneous acral CD8 positive T cell lymphoproliferative disorder and histiocyte and CD8-rich and T-cell-rich lymphoproliferations in associated with a congenital immunodeficiency are not considered to be a form of CD8+ TLPD.
The correct diagnosis of CD8+ TLPD is crucial because of its far more benign clinical behavior than many other types of similarly appearing CD8+ T-cell lymphomas.[9][10][11][12][13]
At presentation, 31 patients with CD8+ TLPD were 29–89 years old (average 52.1 years); 23 were male, 8 were female; 26 had nodules, 5 had plaques; 28 had a single lesion, 2 had bilateral lesions, and 1 had multiple lesions; 18 had a single lesion on the ear, 3 had a single lesion on the nose, 1 had a single lesion on the leg, 4 had a single lesion on the foot, 2 had a single lesion on the arm, 1 had a single lesion on the hand, 1 had a single lesion on a non-acral site behind the ear, and 1 had disseminated lesions at non-acral sites on the head and neck. Among the 26 patients for which this data was available, their lesions had begun and slowly increased in size for 3 to 420 months (median duration 12 months) prior to their being diagnosed.[14] Rarely, patients have also presented with CD8+ TLPD lesions on two other non-acral sites, the thigh or eyelid.[15] TCD8+ TLPD lesions have presented as reddish/purple nodules or plaques measuring up to several centimeters in maximal dimension.[1] These lesions are not ulcerated, i.e., do not have ulcers.[9] Various analyses to define the patients stage, (i.e., extent of disease) at presentation using computed tomography scans and/or bone marrow examinations almost uniformly found that at presentation or thereafter the lesions had not spread to non-cutaneous sites.[14][16][17][18] About 20% of patients that had their CD8+ TLPD lesions disappear in response to treatment will have purely cutaneous recurrences of their lesions.[14] As of 2022,[5] only one patient, after a long history of being repeatedly treated for cutaneous recurrences of CD8+ TLPD, developed a subcutaneous spread of a CD8+ TLPD nasal lesion into the nearby nasal bone and cartilage.[5][19]
Histopathology and immunochemistry
The microscopic histopathology (i.e., examination) of CD8+ TLPD lesions commonly shows a dense infiltration of similarly appearing, medium-sized (or in uncommon cases large or small[14]) CD+ T-cells.[18][2][5][13] In some cases, these T-cells have a monocyte-like appearance and nuclei that are eccentrically located and kidney-shaped.[15] The lesions may also show small collections of B lymphocytes[18] but have few plasma cells or eosinophils.[15] The lesions show no evidence that their cells have invaded blood vessels.[1] In three reported cases, there was an extension of the infiltrate into the nearby subcutaneous fat tissue. The growth rate of these T-cells, as measured by their tissues' proliferation index (a histopathological measurement of how many cells in the lesions are dividing into two daughter cell) or Ki-67 (a measure of the proliferation rate of the lesions individual cells) is usually low.[14][18] The lesions do not have areas of necrosis, i.e., clumps of dead cells.[9] Analyses of the lesions using immunochemistry methods indicate that their cells do not express cytosol protein perforin nor, in most cases, the granule-bound protein granzyme B.[2][7][20] The T-cells in these lesions do express T-cell receptor proteins, CD8 (a transmembrane glycoprotein that is a co-receptor for the T-cell receptor), TIA-1 (i.e., a granule-bound mRNA-binding protein), and in almost all cases (e.g., 26 of 28 cases in one study), the CD68 glycoprotein which is distributed in an unusual and distinctive dot-like pattern around the cell's nucleus.[1][14][15][19][20][21]