D.V. Kazakov

Pyogenic lymphoma of the skin: a peculiar variant of primary cutaneous neutrophil-rich CD30+ anaplastic large-cell lymphoma. Clinicopathological study of four cases and review of the literature

Summary Systemic anaplastic large‐cell lymphoma (ALCL) in human immunodeficiency virus (HIV)‐infected individuals showing an extensive infiltrate of neutrophils has been reported and referred to as ‘neutrophil‐rich’ CD30+ ALCL. Secondary cutaneous involvement has been found in a subset of these cases. We report the clinicopathological features of four immunocompetent patients with primary cutaneous neutrophil‐rich ALCL and present a new histological subtype with a dissolute growth pattern of CD30+ tumour cells. Four HIV‐negative patients presented with rapidly growing solitary or multiple tumours located on the face. Ulceration of the lesions with purulent discharge was a typical finding. Various inflammatory dermatoses were considered clinically in all cases. The histological hallmark was a large number of neutrophils in the infiltrate that masked neoplastic CD30+ anaplastic cells. In two cases, a dissolute growth pattern of anaplastic tumour cells was observed. In two cases, a strong correlation between tumour growth and interleukin (IL)‐8 cytokine pattern as well as the production of IL‐8 by tumour cells was demonstrated. The diagnosis of neutrophil‐rich ALCL is challenging clinically and histologically as the tumour cell compartment is masked by an extensive inflammatory infiltrate of neutrophils and other reactive cells such as histiocytes which may be mainly due to release of IL‐8 by tumour cells. The term ‘pyogenic’ designates the typical feature of this distinct neutrophil‐rich ALCL, namely abscess formation (‘pyo‐’) by cytokines (IL‐8) produced by tumour cells (‘‐genic’). The clinical behaviour of this type is the same as in primary cutaneous CD30+ ALCL with classical histological presentation.

Imiquimod Induces Complete Clearance of a PUVA-Resistant Plaque in Mycosis fungoides

Imiquimod is a topical immune response modifier that binds to Toll-like receptors 7 and 8 and induces α-interferon. We locally applied imiquimod 5% cream (Aldara®) daily for 2 weeks on a PUVA- and retinoid-resistant plaque on the face of a patient with mycosis fungoides. The diagnosis was based on clinical appearance, histology and molecular studies. Most of the disease manifestations showed a clear remission during PUVA therapy combined with low-dose retinoids. However, the plaque on the face was PUVA resistant. Local imiquimod treatment resulted in the complete clearance of the plaque. The patient has now been in complete remission for 12 months.

Blastic natural killer-cell lymphoma of the skin associated with myelodysplastic syndrome or myelogenous leukaemia: a coincidence or more?

We report three patients with blastic natural killer (NK)‐cell lymphoma of the skin associated with myelodysplastic syndrome (MDS) (two patients) or subacute myelomonocytic leukaemia (one patient). In two patients MDS was diagnosed before skin lesions; the patient with leukaemia initially presented with skin lesions. Our patients had several clinical features in common, namely multiple skin lesions with a bruise‐like appearance, involvement of the oral mucosa, and good general status at presentation but very rapid deterioration in the course of the disease. All patients died of disease 4–14u2003months after the diagnosis. Histopathologically, there were cutaneous infiltrates of slightly pleomorphic medium‐sized cells expressing CD4, CD56, terminal deoxynucleotidyl transferase (focally) and being negative for surface CD3, cytotoxic molecules, B‐cell‐associated markers and myelomonocytic markers. Erythrocyte extravasation was seen in all patients. T‐cell receptor genes were in germline configuration. MDS was classified as refractory cytopenia with multilineage dysplasia and ring sideroblasts and refractory anaemia with transition to refractory anaemia with excess of blasts. We reviewed similar cases reported in the literature showing coexistence of blastic NK‐cell lymphoma/leukaemia and MDS or myelogenous leukaemia. We conclude that given an overall limited number of reported cases of blastic NK‐cell lymphoma/leukaemia, its association with various myelodysplastic/myeloproliferative disorders seen in a subset of patients (≈u200315–20%) is more than coincidental and may indicate their common origin.

Detection of clonal rearrangement of T-cell receptor genes in the diagnosis of primary cutaneous CD30+ lymphoproliferative disorders

Background:u2002 Detection of clonality has been reported to be a helpful tool in the diagnosis of cutaneous lymphomas. Monoclonal rearrangement of T‐cell receptor genes (TCR) was reported in fresh frozen tissue of lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large‐cell lymphoma (ALCL), but the diagnostic value of T‐cell clonality in formalin‐fixed, paraffin‐embedded biopsies has so far not been assessed.

Primary cutaneous plasmacytoma: a clinicopathological study of two cases with a long-term follow-up and review of the literature

Background:u2002 Primary cutaneous plasmacytoma (PCP) is a rare type of cutaneous B‐cell lymphoma arising primarily in the skin and derived from clonally expanded plasma cells with a various degrees of maturation and atypia. The disease is rare with only 30 cases reported so far.

Hepatitis C and G viruses in B‐cell lymphomas of the skin

Background:u2002 The etiology of B‐cell lymphoproliferative disorders (LPDs) of the skin has still to be elucidated. So far, Borrelia sp. has been identified as the causative agent of some cases of B‐cell LPDs of the skin. Apart from bacterial pathogens, recent studies suggested that also flaviviruses, in particular hepatitis C (HCV) and G (HGV) viruses, may be involved in the pathogenesis of B‐cell non‐Hodgkins lymphomas (NHLs). Most studies were performed in patients with known HCV infection, but the overall frequency of HCV‐ and HGV‐RNA in tumoral tissue of primary cutaneous B‐cell lymphomas (CBCLs) is unknown.

Superficial Acral Fibromyxoma: Report of Two Cases

Superficial acral fibromyxoma (SAFM) is a rare soft tissue tumor that has recently been delineated as a separate entity. We report 2 cases of SAFM and discuss its pathological features and differential diagnosis. Both patients had lesions on the toe. In 1 patient, the tumor was found after nail extraction, which had been performed for the treatment of onychomycosis, whereas in the other patient the tumor itself was the reason for seeking dermatological assistance. Biopsies from both cases demonstrated similar features. There was a moderately circumscribed, non-encapsulated tumor extending through the whole dermis. The neoplasm was composed of spindle and stellate cells with slight nuclear atypia arranged in a loose storiform, partly fascicular growth pattern. In 1 case, strands of cells with rather wavy nuclei were seen at the periphery of the tumor. Mitotic figures were scarce. The neoplastic cells were embedded in a myxoid stroma with increased numbers of small blood vessels and scattered mast cells. Immunohistochemically, the tumor cells showed weak focal positivity for CD34 and stained negatively for S-100 protein and α-smooth muscle actin. In 1 case epithelial membrane antigen (EMA) was negative, whereas in the second case focal expression of EMA by neoplastic cells was seen. Alcian blue staining revealed abundant mucinous material within the stroma. In conclusion, SAFM represents a distinct entity in the spectrum of cutaneous myxoid tumors. The differential diagnosis of SAFM includes various myxoid neoplasms and tumors with a predilection for distal parts of the extremities.

A case of Sézary's syndrome associated with granulomatous lesions, myelodysplastic syndrome and transformation into CD30-positive large-cell pleomorphic lymphoma

Sézarys syndrome (SS) is a leukaemic variant of mycosis fungoides, a cutaneous T‐cell lymphoma showing distinct clinical, histological, immunological, and genotypic features. We report a 10‐year follow‐up of a patient with SS exhibiting unusual features such as granulomatous skin lesions, transformation to a CD30‐positive large‐cell pleomorphic T‐cell lymphoma, and development of myelodysplastic syndrome and review the cases of SS reported in the literature with these unusual and rare complications.

HHV-8 DNA Sequences in the Peripheral Blood and Skin Lesions of an HIV-Negative Patient with Multiple Eruptive Dermatofibromas: Implications for the Detection of HHV-8 as a Diagnostic Marker for Kaposi’s Sarcoma

Background: Multiple eruptive dermatofibroma (MEDF) is a rare disorder seen in immunocompromised patients, simulating Kaposi’s sarcoma (KS). Whereas KS is strongly associated with human herpesvirus 8 (HHV-8), the virus has never been detected in MEDF until now. Objective: To present a patient with MEDF who showed no signs of immunodeficiency but was seropositive for HHV-8 antibodies and demonstrated HHV-8 DNA both in the peripheral blood and lesional skin of MEDF. Methods: Clinical, histological and serological investigations were performed as well as polymerase chain reaction (PCR) studies and in situhybridization (ISH). Results: A 35-year-old white man with suspected KS was referred for evaluation of multiple pigmented nodules and patches. Biopsies revealed features of dermatofibroma, superficial fibrosing dermatitis and scar. One of the nodular lesions harbored HHV-8 DNA sequences. A faint amplification product was detected in the superficial fibrosing dermatitis lesion, while no HHV-8 sequences were found in normal skin and scar. Whole-blood samples and serum were positive for HHV-8. None of the skin lesions shown to harbor HHV-8 DNA sequences by nested PCR displayed a signal for HHV-8 RNA by ISH. Repetitive peripheral blood examinations did not reveal any serum antibodies against or antigens of HIV. Serum antibodies against the HHV-8 capsid antigen orf 65.2 were detected. Conclusion: Results of PCR studies and ISH indicate that the presence of HHV-8 in the lesional tissue was probably blood-borne due to viremia and not due to viral replication in tumor cells. The presence of HHV-8 is not fully restricted to KS. The differential diagnosis of KS and its simulators should be based on an integrative analysis of all available clinicopathological and molecular data and should not rely exclusively or predominantly on the presence or absence of HHV-8.

Study of HHV‐8 DNA sequences in archival biopsies from lesional skin of Kaposi's sarcoma, various mesenchymal tumors and related reactive conditions

Background: HHV‐8 has been identified as the causative agent of Kaposis sarcoma (KS) and some lymphoproliferative disorders. In addition, there are anecdotal reports on the presence of HHV‐8 in other tumors, especially cutaneous epithelial and mesenchymal neoplasms. The aim of the study was to ascertain the value of identification of HHV‐8 viral DNA sequences in routinely processed, formalin‐fixed, paraffin‐embedded tissues for the diagnosis of Kaposis sarcoma and other mesenchymal tumors.