Diagnostic criteria for CD30+ LPD
| LYP |
| Clinical criteria |
| Recurrent self-healing grouped or disseminated papulonodular skin lesions |
| Note: Self-healing is defined as spontaneous regression of each individual tumor lesion within weeks or months, whether or not new lesions occur. |
| LYP may manifest concurrently with MF, which is typically characterized by patches and eventually plaques or tumors. |
| Histologic criteria |
| LYP type A: Wedge-shaped infiltrate with scattered or clustered CD30+ tumor cells, intermingled with numerous inflammatory cells, such as small lymphocytes, neutrophils, eosinophils, and histiocytes (Figures 3 and 4). Type A is the most common histologic presentation. |
| LYP type B: Epidermotropic infiltrate of small atypical CD30+ or CD30− lymphoid cells with cerebriform nuclei that histologically resembles MF. |
| LYP type C: Cohesive sheets of CD30+ large atypical lymphoid cells with only a few admixed reactive inflammatory cells. |
| LYP type D: Epidermotropic infiltrate of small- to medium-sized atypical CD8+ and CD30+ lymphoid cells that histologically resembles primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma. |
| Immunphenotypically, CD30+ tumor cells express CD4 in most cases, but CD8+ or CD56+ phenotypes have been reported.69 T-cell-associated antigens, such as CD45RO, are expressed with variable loss of pan-T-cell antigens (CD2, CD3, CD5) in LYP. |
| Note: There is a broad differential diagnosis because the presence of large atypically appearing CD30+ lymphoid cells is not restricted to CD30+ LPD but is seen in various inflammatory and infectious disorders.17 |
| PCALCL |
| Clinical criteria |
| Solitary, grouped, or multifocal nodular lesions |
| No clinical evidence of LYP, MF, or other types of CTCL |
| Absence of extracutaneous involvement assessed by staging procedures |
| Histologic criteria |
| Dense nodular dermal infiltrate composed of large pleomorphic, anaplastic, or immunoblastic cells with large, irregularly shaped nuclei and abundant pale or eosinophilic cytoplasm (Figure 5). Clusters of small reactive lymphocytes and eosinophils may be found within and surrounding the tumor cells. |
| Immunphenotypically, CD30+ is expressed by at least 75% of tumor cells. In addition, CD4 or CD8 is expressed in most cases with variable loss of pan-T-cell antigens (CD2, CD3, CD5). |
| Note: In contrast to nodal ALCL, primary cutaneous forms of ALCL lack epithelial membrane antigen and express the cutaneous lymphocyte antigen (HECA-452). Anaplastic lymphoma kinase [ALK-1 (p80)] and t(2;5) translocation are usually absent in PCALCL. If these are present, one needs to be highly suspicious of the lesions being a cutaneous manifestation of underlying systemic ALCL. |
| Borderline cases |
| Cases in which, despite careful clinicopathologic correlation, a definite distinction cannot be made at the time of diagnosis. In most cases, the final diagnosis can be achieved during follow-up based on clinical behavior. |
| Note: It can be challenging and, in individual cases, even impossible to differentiate between LYP and PCALCL in patients presenting with a short history of multifocal papulonodular lesions because, although spontaneous regression of tumors is a hallmark of LYP, this has also been observed in patients with multifocal PCALCL. |
| LYP |
| Clinical criteria |
| Recurrent self-healing grouped or disseminated papulonodular skin lesions |
| Note: Self-healing is defined as spontaneous regression of each individual tumor lesion within weeks or months, whether or not new lesions occur. |
| LYP may manifest concurrently with MF, which is typically characterized by patches and eventually plaques or tumors. |
| Histologic criteria |
| LYP type A: Wedge-shaped infiltrate with scattered or clustered CD30+ tumor cells, intermingled with numerous inflammatory cells, such as small lymphocytes, neutrophils, eosinophils, and histiocytes (Figures 3 and 4). Type A is the most common histologic presentation. |
| LYP type B: Epidermotropic infiltrate of small atypical CD30+ or CD30− lymphoid cells with cerebriform nuclei that histologically resembles MF. |
| LYP type C: Cohesive sheets of CD30+ large atypical lymphoid cells with only a few admixed reactive inflammatory cells. |
| LYP type D: Epidermotropic infiltrate of small- to medium-sized atypical CD8+ and CD30+ lymphoid cells that histologically resembles primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma. |
| Immunphenotypically, CD30+ tumor cells express CD4 in most cases, but CD8+ or CD56+ phenotypes have been reported.69 T-cell-associated antigens, such as CD45RO, are expressed with variable loss of pan-T-cell antigens (CD2, CD3, CD5) in LYP. |
| Note: There is a broad differential diagnosis because the presence of large atypically appearing CD30+ lymphoid cells is not restricted to CD30+ LPD but is seen in various inflammatory and infectious disorders.17 |
| PCALCL |
| Clinical criteria |
| Solitary, grouped, or multifocal nodular lesions |
| No clinical evidence of LYP, MF, or other types of CTCL |
| Absence of extracutaneous involvement assessed by staging procedures |
| Histologic criteria |
| Dense nodular dermal infiltrate composed of large pleomorphic, anaplastic, or immunoblastic cells with large, irregularly shaped nuclei and abundant pale or eosinophilic cytoplasm (Figure 5). Clusters of small reactive lymphocytes and eosinophils may be found within and surrounding the tumor cells. |
| Immunphenotypically, CD30+ is expressed by at least 75% of tumor cells. In addition, CD4 or CD8 is expressed in most cases with variable loss of pan-T-cell antigens (CD2, CD3, CD5). |
| Note: In contrast to nodal ALCL, primary cutaneous forms of ALCL lack epithelial membrane antigen and express the cutaneous lymphocyte antigen (HECA-452). Anaplastic lymphoma kinase [ALK-1 (p80)] and t(2;5) translocation are usually absent in PCALCL. If these are present, one needs to be highly suspicious of the lesions being a cutaneous manifestation of underlying systemic ALCL. |
| Borderline cases |
| Cases in which, despite careful clinicopathologic correlation, a definite distinction cannot be made at the time of diagnosis. In most cases, the final diagnosis can be achieved during follow-up based on clinical behavior. |
| Note: It can be challenging and, in individual cases, even impossible to differentiate between LYP and PCALCL in patients presenting with a short history of multifocal papulonodular lesions because, although spontaneous regression of tumors is a hallmark of LYP, this has also been observed in patients with multifocal PCALCL. |
The final diagnosis should always be based on a careful clinicopathologic correlation.