Cutaneous Infiltrates Research Articles

Penis invalidating cicatricial outcomes in an enlargement phalloplasty case with polyacrylamide gel (Formacryl)

The present article reports the case of a patient subjected to polyacrylamide polymers-composed gel cutaneous infiltration in the penis for cosmetic purposes, resulting in severe invalidating outcomes. A significant tissue reaction to the subcutaneous injection of polyacrylamide gel for the penis enlargement purpose resulted in permanent and invalidating scars both on the esthetic and functional levels. Such a result must be simply taken into account both singly and in the light of the international literature to exclude this method as standard uro-andrologic activity.

Increased expression of chemokines in the skin of chronic proliferative dermatitis mutant mice

Chemokines direct the migration of leukocytes to sites of inflammation and are potential targets for anti-inflammatory therapy. Chronic proliferative dermatitis (cpdm/cpdm) mutant mice develop a persistent eosinophilic dermatitis associated with increased T(H)2 cytokines in the skin. Expression patterns of chemokines in the skin of cpdm/cpdm mice were evaluated to define the mechanisms driving cutaneous infiltration by leukocytes. RNA isolated from the skin of mutant and littermate control mice revealed a significant increase in Ccl1 (TCA-3), Ccl2 (MCP-1), Ccl11 (eotaxin), Ccl17 (TARC), Cxcl10 (IP-10), and the chemokine receptor Ccr3. The concentration of CCL11 protein was increased two- to threefold in the skin of cpdm/cpdm mice by enzyme-linked immunosorbent assay. In vitro culture of primary dermal fibroblasts from cpdm/cpdm and control mice with tumor necrosis factor, IL-4, and IL-13 stimulation did not reveal differences in their ability to secrete CCL11, suggesting that the increased chemokine expression observed in the skin of cpdm/cpdm mice is most likely caused by the increased T(H)2 cytokines in the dermis of this mouse model. Treatment of cpdm/cpdm mice with CCL11-neutralizing polyclonal antibodies did not affect the number of eosinophils in the skin or the severity of the dermatitis. Neutralizing multiple chemokines or chemokine receptors may be necessary to decrease eosinophil accumulation. The cpdm/cpdm mutant mouse is a potentially useful model to determine the role of various chemokines in eosinophil accumulation in chronic inflammation.

Primary cutaneous B-cell lymphoma (marginal zone) with prominent T-cell component and aberrant dual (T and B) genotype; diagnostic usefulness of laser-capture microdissection

The presence of a dominant B- or T-cell clone is an important diagnostic criterion for distinguishing cutaneous lymphomas from lymphoid reactive infiltrates. Rarely, a combined B- and T-cell rearrangement can be detected from a single sample. In such instances, genotypic analysis does not permit differentiation of the coexistence of a T- and B-cell lymphoma from a single clone harbouring a monoclonal rearrangement for both immunoglobulin heavy chain and T-cell receptor genes. We herein report a case of a skin tumour consistent with a dense cutaneous lymphoid infiltrate showing a double prominent B- and T-cell component. A dual B- and T-cell clonality was detected by polymerase chain reaction from whole-tissue DNA sample. Genotypic analysis with DNA, obtained after laser-assisted microdissection from the B-cell population, again showed both T- and B-cell monoclonal rearrangements. Conversely, the microdissected T-cell population did not reveal a clonal pattern. The diagnosis of cutaneous B-cell lymphoma with a dual B- and T-cell genotype was established. This description illustrates the diagnostic usefulness of laser-capture microdissection in cutaneous lymphomas presenting dual genotype.

Cutaneous Lymphoid Hyperplasia and Other Lymphoid Infiltrates of the Breast Nipple

This study characterizes the clinicopathological spectrum of lymphoproliferations involving the breast nipple and/or areola. Morphologic, immunohistochemical, molecular-genetic, and clinical features of 58 specimens from 56 patients were analyzed. They were re-diagnosed as cutaneous lymphoid hyperplasia (CLH, n = 44); other benign lymphoid infiltrates (OBLI, n = 8); peripheral T-cell lymphoma, not otherwise specified (n = 1); cases with overlapping features of CLH and B-cell lymphoma (n = 3), one of them composed of spindle cells. Cutaneous lymphoid hyperplasia infiltrates were dense, composed mainly of B cells forming follicles with germinal centers (GC). Cutaneous lymphoid hyperplasia frequently showed features suggesting a malignancy as coalescing follicles with non-polarized germinal centers lacking mantle zones, and smudged infiltrates of lymphoid cells spreading into collagen (often as "Indian files"), smooth muscle, vessel walls, and nerve sheaths. Only two cutaneous lymphoid hyperplasias recurred; otherwise all patients are without disease (mean follow-up 62 months). Monoclonal rearrangement of immunoglobulin heavy chain gene was detected in five, and of T-cell receptor gamma gene in two cutaneous lymphoid hyperplasias using polymerase chain reaction (PCR), but the patients fared well too. In 47% of cases Borrelia burgdorferi was detected by polymerase chain reaction and/or serology, of which one was monoclonal. We conclude that cutaneous lymphoid hyperplasia is the most common lymphoproliferation of the breast nipple, rarely recognized clinically, and often overdiagnosed histologically as lymphoma.

Early B-cell chronic lymphocytic leukemia presenting as cutaneous lesions with a normal peripheral blood lymphocyte count

To the Editor: B-cell chronic lymphocytic leukemia (B-CLL) is similar to small lymphocytic lymphoma (SLL), having identical histopathologic and immunophenotypic features. However, a diagnosis of CLL requires a clonal population of typical morphology and immunophenotype in blood and bone marrow, even with normal lymphocyte counts.1 We report two cases of CLL presenting with only cutaneous infiltrates without lymphocytosis or lymphadenopathy.

Recurrent and self-healing cutaneous monoclonal plasmablastic infiltrates in a patient with AIDS and Kaposi sarcoma

Infection with human immunodeficiency virus (HIV) increases the risk of developing non-Hodgkin lymphoma. Plasmablastic lymphoma (PBL) is a rare variant of diffuse large cell lymphoma that often involves the oral cavity of HIV+ patients. It is characterized by immunoblastic morphology and plasma cell phenotype. Cutaneous involvement in PBL appears to be rare. We report a 44-year-old man with AIDS and Kaposi sarcoma (KS) previously treated with doxorubicin who, following treatment with highly active antiretroviral therapy, developed an erythematous infiltrated nodule on the right arm. Histology showed subcutaneous fat necrosis and clusters of atypical large plasma cells (plasmablastic cells). Immunohistochemistry revealed lambda light chain restriction. Epstein-Barr virus (EBV) mRNA was detected by in situ hybridization within the plasmablastic cells. Polymerase chain reaction amplification with specific primers for human herpesvirus 8 (HHV-8) performed on the skin biopsy specimen detected a specific band. A complete screening (bone marrow biopsy, computed tomographic scan, radiological survey) disclosed no abnormalities. The lesion resolved spontaneously after 3 months. Two years later an infiltrated plaque developed on the abdominal wall. The clinical and histopathological features of this new lesion were similar to those observed 2 years previously. No evidence of extracutaneous involvement was detected. The lesion again resolved spontaneously after 25 days. PBL may be seen in patients with transplants or receiving chemotherapy, but is usually observed in patients with advanced AIDS. The observation of recurrent self-healing EBV- and HHV-8-associated cutaneous monoclonal plasmablastic infiltrates, in a patient with AIDS and KS, expands the clinical spectrum of AIDS-associated plasmablastic lymphoproliferative disorders.

‘Specific’ cutaneous infiltrate of B‐cell chronic lymphocytic leukemia at the site of a florid herpes simplex infection

Specific cutaneous infiltrates in patients with leukemia generally carry a grim prognosis. However, non-neoplastic skin diseases may be associated with recruitment of normal and neoplastic leukocytes circulating in the peripheral blood. In those instances, neoplastic cells may be detected in skin lesions without an adverse effect on prognosis. In a patient with B-cell chronic lymphocytic leukemia, a specific infiltrate developed at the site of a florid herpes simplex infection. Clinically, the lesion presented itself as an ulcerated tumor. Histopathologically, the lesion was characterized by a dense, diffuse infiltrate of small hyperchromatic lymphocytes throughout the entire dermis. Lymphocytes showed an aberrant CD20(+)/CD43(+)/CD5(+) phenotype of neoplastic B cells, and monoclonal rearrangement of immunoglobulin gamma genes could be demonstrated by polymerase chain reaction. Although criteria for leukemia cutis were fulfilled, the patient did well. The cutaneous infiltrate of neoplastic cells seemed to be part of a physiologic response to the antigenic stimulus, rather than indicating an exacerbation of leukemia. Ziemer M, Bornkessel A, Hahnfeld S, Weyers W. 'Specific' cutaneous infiltrate of B-cell chronic lymphocytic leukemia at the site of a florid herpes simplex infection.

The usefulness of clonality for the detection of cases clinically and/or histopathologically not recognized as cutaneous T-cell lymphoma

The determination of clonality has proven to be a useful adjunct to the diagnosis of cutaneous lymphocytic infiltrates. It is considered particularly helpful for the distinction of mycosis fungoides (MF) and inflammatory dermatoses. To verify the sensitivity of the polymerase chain reaction (PCR)-heteroduplex analysis of T-cell receptor gamma-chain gene (TCRgamma) rearrangements in patients with MF and to establish whether a clinicopathological re-evaluation of lesions previously unclassified or considered to be non-neoplastic entities but found to be monoclonal allowed the recognition of additional cases of MF. Included in the study were 116 patients, seen at our Institute from April 2002 to September 2003 and tested for TCRgamma rearrangements. Thirty-six patients were affected by clinically and histopathologically proven MF, while the remaining 80 cases had not been classified or had been classified as non-neoplastic entities. The sensitivity of the molecular analysis was determined on the basis of the results obtained in the 36 patients with MF. The 29 cases of the second series of patients found to be monoclonal were clinically and histopathologically re-evaluated. Clonal rearrangements were found in 87.5% of patients with plaque stage MF and in 20% of those with patch stage MF. The clinicopathological re-evaluation allowed us to reclassify 15 of 29 monoclonal cases of the second series of patients as MF. The study showed that the PCR-heteroduplex technique can determine a high percentage of monoclonality only in plaque stage MF. However, in spite of the low sensitivity of the method, several cases previously unrecognized could be reclassified as MF when their clinical and histopathological features were re-evaluated taking into account the clonality of the lymphocytic infiltrate.

Inflammatory dermatoses mimicking malignancy (pseudolymphoma)

Interpretation of cutaneous lymphoid infiltrates is one of the most troublesome areas of diagnostic dermatopathology. The term ‘pseudolymphoma’ has been used to classify cases of benign lymphoid infiltrates that mimic lymphoid malignancy. Pseudolymphomas can be categorized according to predominant cell type (B cell, T cell and mixed) and pattern of inflammation (including band-like and nodular). Examples of T-cell, B-cell and mixed pattern pseudolymphomas are illustrated, including solitary pseudolymphomatoid lichenoid lesion, pseudolymphomatoid drug reaction, immunosuppression-associated lymphoproliferative disorder and lymphocytoma cutis. The majority of cases can be diagnosed and managed on the basis of clinical history, light microscopic findings and follow-up. In difficult cases, the usefulness and limitations of immunohistochemistry and molecular studies are discussed. The light microscopic, immunohistochemical and molecular features should be interpreted in the context of the clinical information, with direct discussion between dermatologist and histopathologist in difficult cases.

Drug-induced toxic epidermal necrolysis and pancytopenia: A puzzling association

The molecular mechanisms involved in the pathogenesis of toxic epidermal necrolysis (TEN) remain not fully understood. We report a unique case of antibiotic-induced TEN developed in a patient who also suffered from prolonged severe methotrexate-induced pancytopenia. The objective of the study was to explore the nature of the cutaneous inflammatory infiltrate and the density in dermal dendrocytes (DD). Immunohistochemistry was used to identify activated T lymphocytes (CD45R0), monocyte-macrophages (Mac 387, CD68), DD (Factor XIIIa), and Langerhans cells (CD1a). The proliferation marker (Ki67) and the antibody to Fas receptor (CD95R) were also used to assess the distribution of the germinative pool of keratinocytes and the FAS-related apoptotic process, respectively. Numerous Factor XIIIa+ DD were present in the papillary dermis with only sparce perivascular CD45RO+ T lymphocytes and scattered CD68+ or Mac 387+ macrophages. Double immunostainings revealed that a minority of Factor XIIIa+ DD co-expressed the CD68 glycoprotein (a marker of phagocytic activity). No cells co-expressed factor XIIIa and Mac 387 immunoreactivities. CD45RO+ T lymphocytes, CD68+ and Mac 387+ macrophages were absent in the epidermis. The expression of CD95R was present although restricted to the basal keratinocytes, while the L1-protein (Mac 387+) was diffusely present in the epidermis. Langerhans cells (CD1a+) were sparce, but normal in distribution. The presence of a great number of Factor XIIIa+ DD without any possible recent recruitment from bone marrow suggests that these cells differentiated from resident cells of the skin. Indeed, there was no co-expression of Factor XIIIa and L1-protein, thus showing the absence of recruitment from monocytes. The simultaneous over-expression of Factor XIIIa and CD68 in some DD indicates some phagocytic activity. In view of the absence of inflammatory cells in the epidermis, keratinocytes appeared responsible for their own destruction through CD95-mediated and/or calcium-dependent apoptotic pathways. This finding entails that TEN treatments should target the keratinocyte metabolism rather than the circulating inflammatory cells which presumably play a limited role, if any, in the epidermal destructive process.

Fatal subcutaneous panniculitis‐like T‐cell lymphoma with interface change and dermal mucin, a dead ringer for lupus erythematosus

We report a 48-year-old man who presented with ulcerated plaques and nodules of the lower extremities. Skin biopsies revealed a dense lymphocytic infiltrate involving the dermis and the subcutis in a lobular and septal pattern. No overt cytological atypia was present. Notably, several features resembling lupus erythematosus were present, including vacuolar interface change and abundant dermal mucin deposition. The patient developed pulmonary nodules, and a lung biopsy showed a perivascular and interstitial lymphoid infiltrate without overt atypia. The cutaneous and pulmonary lymphoid infiltrates showed similar immunohistochemical profiles: CD3(+) CD4(-) CD8(+/-) CD56(+). Monoclonal rearrangements of the T-cell receptor gamma gene with similar migration patterns were identified from both locations. The patient developed fatal hemophagocytic syndrome, involving liver, spleen, lymph nodes, and bone marrow. This case is one amongst the rare reports of subcutaneous panniculitis-like T-cell lymphoma with systemic involvement.

Cutaneous Lymphocytic Infiltrates

Cutaneous Lymphocytic Infiltrates

Intrathoracic Myeloid Sarcoma

Abstract: Myeloid sarcoma, previously called granulocytic sarcoma or chloroma, is an extramedullary manifestation of leukemia, most often seen in the monocytic form of acute myeloid leukemia (AML). Myeloid sarcoma may arise before, concurrent with, or after the diagnosis of AML, chronic myelogenous leukemia (CML), or myelodysplastic syndrome (MDS) is made. Common sites of involvement include cutaneous or gingival infiltration of leukemic cells, lymph nodes, small intestine, mediastinum, epidural sites, uterus, and ovary. We report a patient with monoblastic sarcoma, an uncommon variant of noncutaneous, extramedullary acute leukemia that is exclusively of monoblastic derivation. The patient presented with lung involvement, mediastinal lymphadenopathy, pleural effusion, and superior vena cava (SVC) syndrome. He also had tracheobronchial tree compression. His symptoms responded to chemotherapy. We believe ours is the first case of monoblastic sarcoma involving the lung. The relevant literature dealing with intrathoracic myelocytic sarcoma is also reviewed.

Loxosceles Sphingomyelinase Induces Complement-Dependent Dermonecrosis, Neutrophil Infiltration, and Endogenous Gelatinase Expression

Envenomation by the spider Loxosceles can result in dermonecrosis and severe ulceration. Our aim was to investigate the role of the complement system and of the endogenous metalloproteinases in the initiation of the pathology of dermonecrosis. Histological analysis of skin of rabbits injected with Loxosceles intermedia venom and purified or recombinant sphingomyelinases showed a large influx of neutrophils, concomitant with dissociation of the collagenous fibers in the dermis. Decomplementation, using cobra venom factor, largely prevented the influx of neutrophils, while influx of neutrophils was also reduced in genetically C6-deficient rabbits, suggesting roles for both C5a and the membrane attack complex in the induction of dermonecrosis. However, C-depletion and C6 deficiency did not prevent the haemorrhage and the collagen injury. Zymography analysis of skin extracts showed the induction of expression of the endogenous gelatinase MMP-9 in the skin of envenomated animals. Rabbit neutrophils contained high levels of MMP-9, expression of which was further increased after incubation with venom, suggesting that these cells may be a source of the MMP-9 found in the skin of envenomated animals. Furthermore, skin fibroblasts also secreted MMP-9 and MMP-2 upon incubation with venom, suggesting that locally produced MMPs can also contribute to proteolytic tissue destruction.

Immunophenotyping of the chronic cutaneous infiltrate in patients with atopic dermatitis (AD)

Immunophenotyping of the chronic cutaneous infiltrate in patients with atopic dermatitis (AD)

Fatal Subcutaneous Panniculitis‐Like T‐Cell Lymphoma (Sptcl) with Interface Change and Dermal Mucin, A Dead‐Ringer for Lupus Erythematosus

We report a 48‐year‐old male who presented with ulcerated plaques and nodules of the lower extremities. Skin biopsies revealed a dense lymphocytic infiltrate involving the dermis and the subcutis in a lobular and septal pattern. No overt cytological atypia was present. Notably, several features resembling lupus erythematosus were present, including vacuolar interface change and abundant dermal mucin deposition. The patient developed pulmonary nodules, and a lung biopsy showed a perivascular and interstitial lymphoid infiltrate without overt atypia. The cutaneous and pulmonary lymphoid infiltrates showed similar immunohistochemical profiles: CD3+CD4−CD8+/−CD56+. Monoclonal rearrangements of T‐cell receptor gamma gene with similar migration patterns were identified from both locations. The patient developed fatal hemophagocytic syndrome, involving liver, spleen, lymph nodes, and bone marrow. This case is amongst rare reports of subcutaneous panniculitis‐like T‐cell Lymphoma (SPTCL) with systemic involvement.

Cutaneous and Systemic Plasmacytosis

Background: Plasmacytosis is a rare entity, which may manifest with cutaneous patches and plaques and may subsequently progress to involve extracutaneous sites. First described in Japan by Kimura K et al in 1983, most cases have been reported in patients of Asian descent. Observation: We report a case of plasmacytosis in a 52‐year‐old Hispanic woman, who presented ten years ago with cutaneous infiltrates of plasma cells and polyclonal hypergammaglobulinemia. Numerous (immunohistochemical, molecular, serologic) studies failed to demonstrate a clonal lymphoplasmacellular neoplasm, collagen vascular disease or chronic infection. Her course has been slowly progressive with new plaques developing on the integument. Plasma cells have since infiltrated gastric and esophageal mucosa, the left temporal artery and lymph nodes. The disease has been resistant to various therapeutic approaches. Conclusions: Our case provides long‐term follow‐up of a patient with plasmacytosis and illustrates the chronic progressive course of this disease over a 10‐year course with unique involvement of the temporal artery and gastrointestinal mucosa.

Cutaneous and Systemic Plasmacytosis

A 67‐year‐old Chinese man presented with a longstanding history of asymptomatic, brown‐red macules that diffusely involved his trunk and the extremities and was associated with generalized lymphadenopathy. His serum protein electrophoresis revealed a polyclonal hypergammaglobulinemia. No monoclonal Bence Jones protein was detected in the urine. Flow cytometry of his peripheral blood revealed a normal polyclonal population of B and T cells. Histopathologic examination demonstrated a dense nodular infiltrate of lymphocytes and numerous mature plasma cells in the reticular dermis. Immunoperoxidase studies for kappa and lambda light chains failed to demonstrate clonality. In addition, immunoglobulin gene rearrangement studies failed to reveal a monoclonal band. A bone marrow biopsy showed no abnormality. Cutaneous and systemic plasmacytosis is a rare lymphoproliferative disorder that is an important consideration in the differential diagnosis of cutaneous infiltrates in which plasma cells predominate.

Extensive Basal Cell Carcinoma and Disseminated Lesions in Hand-Schüller-Christian disease

Sir, Langerhans’ cell histiocytosis (LCH) includes four clinical entities with a common characteristic of infiltration of LC in different tissues. Biopsy of suspicious lesions and staining for CD1a and S100 protein or antilangerin are needed to establish a definitive diagnosis of LCH. Electron microscopy to identify Birbeck granules is performed less frequently because of time and cost constraints (1, 2). The pathogenesis remains unclear. A neoplastic aetiology has been suggested due to the existence of a single clone in the infiltration, although no cytogenetic abnormalities have been found (3, 4). Most investigators consider LCH to result from an immunological dysfunction (2, 5, 6). The presence of aggregates of other immunologically active cells, decreased numbers of suppressor T lymphocytes and high levels of cytokines in the lesions suggest an exaggerated physiological response of LC to an antigen, or an appropiate response to abnormal signals from other immune cells (1, 7, 8). Although numerous facts are known about the cell mediators, it has not been possible to prove the participation of any factor in the unchaining of the clonal proliferation of the cells in the LCH (9). We present here a new case of basal cell carcinoma (BCC) in association with one type of LCH, HandSchuller-Christian disease, with a probably late specific cutaneous infiltration of the LC.

The application of a monoclonal antibody to CD62L on paraffin‐embedded tissue samples in the assessment of the cutaneous T‐cell infiltrates

A reduction in the expression of the pan T-cell markers CD7 and CD62L supports an endogenous T-cell dyscrasia. Previously, clone availability for CD62L restricted its application to frozen tissue sections. A nonavidin/biotin technique to examine CD3, CD62L, and CD7 in paraffin formalin-fixed tissue in non-neoplastic and neoplastic T-cell infiltrates. In the reactive group, CD62L manifested a 15 and 22% reduction in epidermal and dermal staining, respectively; there was a 42 and 31% reduction in epidermal and dermal CD7 staining. In lymphomatoid hypersensitivity, CD62L showed a 24 and 9% reduction in epidermal and dermal staining, respectively; CD7 staining demonstrated reduced staining by 70 and 66% in the epidermis and dermis. In the non-lymphomatous endogenous T-cell dyscrasia and lymphoma categories, an 80% diminution in CD62L and CD7 expression was seen. CD62L can be successfully applied in formalin-fixed tissue and exhibits enhanced specificity compared to CD7 in the evaluation of cutaneous T-cell infiltrates. Both CD62L and CD7 in paraffin-embedded, formalin-fixed tissue are useful diagnostic adjuncts, especially in regard to the discrimination of lymphomatoid hypersensitivity reactions from true endogenous T-cell dyscrasia.