Stenotrophomonas maltophilia skin infection in an immunocompetent patient: Primary cutaneous CD30+ T-cell lymphoproliferative disorder or pseudolymphoma?

Cutaneous pseudolymphomas are a wide group of diseases mimicking cutaneous lymphoma. They comprise several skin conditions with different etiopathogenesis, clinical-pathological features, and prognosis, which may occur in the absence of an identifiable trigger factor or after administration of medications or vaccinations, tattoos, infections, or arthropod bites. They present with different manifestations: from solitary to regionally clustered lesions, up to generalized distribution and, in rare cases, erythroderma. They persist variably, from weeks to years, and resolve spontaneously or after antibiotics, but may recur in some cases. CD30+ T-cell pseudolymphomas are characterized by the presence of large, activated lymphoid cells, generally in response to viral infections, arthropod assault reactions, and drug eruptions. Stenotrophomonas maltophilia is a ubiquitous Gram-negative bacillus responsible for opportunistic infections in immunocompromised patients. Infection of intact skin in immunocompetent patients is particularly rare. Here, we report a case of a man presenting an isolated nodule histopathologically mimicking a primary cutaneous CD30+ T-cell lymphoproliferative disorder.

Recurrent episodes of palpable migratory arciform erythema associated with IVIg infusions.

Palpable migratory arciform erythema (PMAE) is an uncommon T cell pseudolymphoma characterized by erythematous, annular-to-arciform papules and plaques. Although the eruption is self-limited in most cases, recurrences are routine. Diagnosis requires attention to clinical history as well as histopathologic analysis, which allow for differentiation from other T cell pseudolymphomas and gyrate erythemas. A common triggering factor has not been identified. We report a 60-year-old man who developed PMAE after IVIg infusion. Interestingly, although the individual eruptions were self-limited and resolved after several weeks, subsequent infusions predictably resulted in recurrence of PMAE, confirming the association. To our knowledge, this is the first reported case of recurrent PMAE in association with IVIg infusions.

Cutaneous B cell pseudolymphoma treated with rituximab and methotrexate.

Cutaneous B cell pseudolymphoma (CBPL), or cutaneous lymphoid hyperplasia, is the most common pseudolymphoma. It typically responds well to local treatment and follows a benign course. Herein, we describe the unique case of a patient with CBPL that was refractory to a variety of treatments, with subsequent response to rituximab followed by methotrexate. This case explores the complex interplay of T and B lymphocytes, and the potential role of perifollicular T cells in treatment resistant CBPL. Further, it describes the additive therapeutic effect of rituximab and methotrexate to target both B cell and T cell populations in CBPL, a strategy already employed in a number of other conditions.

Pseudolymphomatous Atypical Fibroxanthoma.

Atypical fibroxanthoma is a rare mesenchymal skin tumor of intermediate malignancy that typically occurs on sun-damaged skin of elderly patients. Histologically, it is composed of pleomorphic cells with hyperchromatic nuclei and abundant cytoplasm, commonly arranged in a spindle cell pattern. Different histologic variants have been described during the past years. We present a case of atypical fibroxanthoma containing a dense inflammatory infiltrate, which in conjunction with the existence of immunoblast-like and Reed-Sternberg-like neoplastic cells could be misinterpreted as a lymphoid neoplasm. Immunohistochemical studies revealed strong positivity of tumor cells for CD10 and negativity for cytokeratins, p63, p40, S100, SOX10, ERG, actin, desmin, B and T-cell markers, BCL6, CD15, and CD30. The inflammatory infiltrate contained a mixed reactive T- and B-cell population with negative T-cell receptor and immunoglobulin heavy rearrangements. We discuss the differential diagnosis of this entity in which clinical, immunohistochemical, and molecular features are essential to avoid the diagnosis of a lymphoproliferative disease.

CD8-positive pseudolymphoma in lues maligna and human immunodeficiency virus with monoclonal T-cell receptor-beta rearrangement.

A 42-year-old Caucasian man suffered from disseminated plaques and ulcerated nodules for 6 weeks. He had weight loss and generalized lymphadenopathy. Underlying diseases were not known up till then. Based on a skin biopsy, the diagnosis of CD8-positive cutaneous T-cell lymphoma, type mycosis fungoides was made in a pathological reference center for lymphoma. A reproducible T-cell receptor (TCR)-beta rearrangement was detectable. Before starting therapy, a new biopsy was taken and the previous diagnosis was re-evaluated taking clinical images and symptoms into account. Based on both, the diagnosis of a CD8+ pseudolymphoma in lues maligna and human immunodeficiency virus was made. We highlight histopathologic clues for the correct diagnosis, and we emphasize the indispensability of clinical-pathological correlation. Furthermore, we discuss the differential diagnosis of CD8+ lymphoproliferative disorders.

T-cell pseudolymphoma in recurrent herpes simplex virus infection.

BACKGROUND: In cases of herpes virus infection without typical histologic (and clinical) signs it is difficult to achieve the correct diagnosis by histology alone. Some of those cases are prone to be misdiagnosed as cutaneous lymphoma. METHODS: This retrospective study included five patients with herpes simplex virus (HSV)-associated pseudolymphoma. We investigated clinical, histomorphologic and immunophenotypic features of all patients. RESULTS: All biopsy specimens presented a superficial and deep perivascular lymphohistiocytic infiltrate with epidermotropism, atypia and admixed plasma cells to varying degrees. Four of five samples showed lining-up of lymphocytes in the junctional zone with predominance of CD8+ lymphocytes, in contrast to the dermal part (inverse CD8:CD4 ratio). Papillary edema was found in four of five cases. Clinically, patchy erythema located on the buttocks and adjacent areas was typical, sometimes with erosions and crusts. Medical history of recurrent blisters, pain or itching was additionally helpful. CONCLUSION: We point out subtle but consistent histomorphologic criteria, which were helpful to diagnose HSV-associated pseudolymphoma in context with the clinical presentation.

Red tattoo-related mycosis fungoides-like CD8+ pseudolymphoma.

Cutaneous reactions to red tattoo pigment rarely manifest as pseudolymphomatous reactions. We describe an exceedingly rare case of red tattoo-related T-cell predominant pseudolymphoma microscopically mimicking mycosis fungoides. Careful clinicopathological correlation was required to obtain the correct diagnosis and aid in an effective treatment course.

Cutaneous intravascular CD30+ T-cell pseudolymphoma occurring in a regressing keratoacanthoma.

Cutaneous intravascular CD30+ pseudolymphoma is an uncommon incidental finding that may mimic intravascular or angiotropic lymphoma. We describe a 78-year-old female with a traumatized regressing keratoacanthoma on her left cheek. A shave biopsy revealed intravascular staining of atypical lymphocytes positive for CD45, CD3 and CD30. Clinical exam revealed no other evidence of lymphoma, the patient denied constitutional symptoms, and routine blood work was normal. The patient is healthy and doing well 28 months after her first visit. CD30+ pseudolymphoma should be distinguished from malignant intravascular lymphoproliferative disorders.

Treatment of Cutaneous Pseudolymphoma: A Systematic Review.

Cutaneous pseudolymphoma (CPL) is a reactive polyclonal T- or B-cell lymphoproliferative process. CPL may appear as localized or disseminated skin lesions. While most cases of CPL are idiopathic, they may also occur as a response to, for example, contact dermatitis, arthropod reactions, and bacterial infections. CPL can be classified based on its clinical features, but all variants have similar histopathological patterns of either predominantly B-cell infiltrates, T-cell infiltrates, or mixed T/B-cell infiltrates. The prognosis of CPL is good, but the underlying disease process should be taken into account. If an antigenic stimulus is identified, it should be removed. In patients with idiopathic CPL, a close follow-up control strategy should be adopted. The aim of this systematic review is to summarize all reported treatments for CPL. The review was based on articles from the PubMed database, using the query "skin pseudolymphoma treatment", English and German, about "human" subjects, and published between 1990 and 2015 documenting adequate treatment and/or aetiology. Mainly individual case reports and small case series were found. Treatment options include topical and intralesional agents, systemic agents, and physical modalities. The final part of the review proposes a treatment algorithm for CPL according to each aetiology, based on the literature of the last 25 years. Future research should focus on randomized controlled trials and studies on long-term outcomes, which were not identified in the current review.

Mixed Lichenoid and Follicular T- and B-Cell Lymphoid Reaction to Red Tattoos With Monoclonal T Cells.

Pseudolymphomatous reactions have been described to occur in tattoos. Most cases have exhibited T-cell predominance and polyclonal T-cell receptor gene rearrangements. One case with monoclonal IgH gene rearrangements progressed into B-cell lymphoma. Lichenoid infiltrates are commonly described but lymphoid follicles much less frequently. We report a case with mixed lichenoid and follicular T- and B-cell reaction to red tattoos. The histopathology and the immunohistochemical studies were constant with a mixed T- and B-cell pseudolymphoma, the IgH gene rearrangement study was polyclonal, but the T-cell receptor gene rearrangement study was monoclonal. The patient who responded to intralesional corticosteroid injections remains under close scrutiny.

Cutaneous borreliosis associated with T cell-predominant infiltrates: a diagnostic challenge.

BACKGROUND: With the exception of erythema migrans, Borrelia infection of the skin manifests much more commonly with B cell-rich infiltrates. T cell-rich lesions have rarely been described. OBJECTIVE: We report a series of 6 patients with cutaneous borreliosis presenting with T cell-predominant skin infiltrates. METHODS: We studied the clinicopathologic and molecular features of 6 patients with T cell-rich skin infiltrates. RESULTS: Half of the patients had erythematous patchy, partly annular lesions, and the other patients had features of acrodermatitis chronica atrophicans. Histopathology revealed a dense, band-like or diffuse dermal infiltrate. Apart from small, well differentiated lymphocytes, there were medium-sized lymphocytes with slight nuclear atypia and focal epidermotropism. An interstitial histiocytic component was found in 4 cases, including histiocytic pseudorosettes. Fibrosis was present in all cases but varied in severity and distribution. In 5 patients, borrelia DNA was detected in lesional tissue using polymerase chain reaction studies. No monoclonal rearrangement of T-cell receptor gamma genes was found. LIMITATIONS: This retrospective study was limited by the small number of patients. CONCLUSION: In addition to unusual clinical presentation, cutaneous borreliosis can histopathologically manifest with a T cell-rich infiltrate mimicking cutaneous T-cell lymphoma. Awareness of this clinicopathologic constellation is important to prevent underrecognition of this rare and unusual presentation representing a Borrelia-associated T-cell pseudolymphoma.

T cell lymphomatoid contact dermatitis: a challenging case and review of the literature.

Lymphomatoid contact dermatitis is a pseudolymphoma with clinical and histological features of allergic contact dermatitis and cutaneous T cell lymphoma. Incorrect diagnosis may lead to unnecessary testing, unnecessary treatment, or patient harm. The objective of this study is to present a case to demonstrate the diagnostic challenge and overlap between allergic contact dermatitis and cutaneous T cell lymphoma in a patient with lymphomatoid contact dermatitis caused by methylchoroisothiazolinone/methylisothiazolinone and paraben mix, and to review the existing literature in order to summarize the demographics, clinical features, allergens and treatments reported for lymphomatoid contact dermatitis. A search of major scientific databases was conducted for English-language articles reporting cases of lymphomatoid contact dermatitis or additional synonymous search headings. Nineteen articles with a total of 23 patients were analysed. Lymphomatoid contact dermatitis was more common in men, with an average age of 58.5 years. Fourteen unique allergens were identified and confirmed by patch testing. However, no single test or study was diagnostic of lymphomatoid contact dermatitis. Allergen avoidance was the most useful management tool, but selected patients required topical or systemic immunosuppression. In conclusion, without specific diagnostic features, evaluation for lymphomatoid contact dermatitis should include a thorough history and examination, patch testing, and biopsy with immunohistochemistry and clonality studies.

IgG4-related skin disease.

IgG4-related disease (IgG4-RD) is a recently established clinical entity characterized by high levels of circulating IgG4, and tissue infiltration of IgG4(+) plasma cells. IgG4-RD exhibits a distinctive fibroinflammatory change involving multiple organs, such as the pancreas and salivary and lacrimal glands. The skin lesions of IgG4-RD have been poorly characterized and may stem not only from direct infiltration of plasma cells but also from IgG4-mediated inflammation. Based on the documented cases together with ours, we categorized the skin lesions into seven subtypes: (1) cutaneous plasmacytosis (multiple papulonodules or indurations on the trunk and proximal part of the limbs), (2) pseudolymphoma and angiolymphoid hyperplasia with eosinophilia (plaques and papulonodules mainly on the periauricular, cheek and mandible regions), (3) Mikulicz disease (palpebral swelling, sicca syndrome and exophthalmos), (4) psoriasis-like eruption (strikingly mimicking psoriasis vulgaris), (5) unspecified maculopapular or erythematous eruptions, (6) hypergammaglobulinaemic purpura (bilateral asymmetrical palpable purpuric lesions on the lower extremities) and urticarial vasculitis (prolonged urticarial lesions occasionally with purpura) and (7) ischaemic digit (Raynaud phenomenon and digital gangrene). It is considered that subtypes 1-3 are induced by direct infiltration of IgG4(+) plasma cells, while the other types (4-7) are caused by secondary mechanisms. IgG4-related skin disease is defined as IgG4(+) plasma-cell-infiltrating skin lesions that form plaques, nodules or tumours (types 1-3), but may manifest secondary lesions caused by IgG4(+) plasma cells and/or IgG4 (types 4-7).

Flow cytometry CD4(+)CD26(-)CD38(+) lymphocyte subset in the microenvironment of Hodgkin lymphoma-affected lymph nodes.

Hodgkin lymphoma (HL) is traditionally diagnosed by the presence of neoplastic Hodgkin and Reed-Sternberg (HRS) cells found in minority within a typical inflammatory microenvironment. It is now recognized that the majority of these T CD4 cells are T regulatory (Treg) and play an important immunosuppressive role and contribute to tumour persistence. Flow cytometric immunophenotyping of lymphocytes was performed on lymph node samples over a 12-year period (2000-2012) to identify the Hodgkin-specific subset and potential biomarkers related to Treg cells. CD3, CD19 and T CD4(+)CD26(-)CD38(+) subsets were measured in the lymphocytic infiltrate of 108 consecutive lymph node samples concurrently diagnosed histologically as HL and in 43 cases of benign reactive lymphoid hyperplasia (BRLH). HL, compared to BRLH, shows statistically significant differences within the reactive microenvironmental population: decreased CD19(+) cells (23 % vs 39 %; p < 0.001), increased CD3(+) (74 % vs 58 %; p < 0.001) and CD4(+)CD26(-)CD38(+) cells (38 % vs 11.5 %; p < 0.001). By using the co-expressed markers CD38 and CD26 for logistic analysis, the obtained receiver operating characteristic (ROC) curves confirm that the CD4(+)CD26(-)CD38(+) subset is strongly expressed in HL (ROC AUC = 0,8639). Flow cytometric detection of CD4(+)CD26(-)CD38(+) cells seems able to identify the cellular microenvironmental pattern in HL and to distinguish it from BRLH. Although there is extensive experience in flow cytometric analysis of non-HL, it is not routinely applied in cases of HL and our findings suggest that it may be useful in quickly and easily characterizing its cellular para-neoplastic inflammatory background.

HIV-related CD8+ cutaneous pseudolymphoma: efficacy of methotrexate.

Human immunodeficiency virus (HIV)-related CD8+ cutaneous pseudolymphoma (CD8+ cytotoxic T cell skin infiltrative disease) is an inflammatory process resulting from a massive infiltration of the skin by activated, oligoclonal, HIV-specific, cytotoxic T lymphocytes. Usually, CD8+ cutaneous pseudolymphoma affects patients with a deep immunosuppression, and is rare in patients with mild immunosuppression. In deeply immunocompromised patients, highly active antiretroviral therapy (HAART) is considered as the first-line treatment. In contrast, the choice of therapy in moderately immunocompromised patients and/or patients already receiving HAART remains nonconsensual. We report a case of HIV-related CD8+ cutaneous pseudolymphoma in a moderately immunocompromised patient who was successfully and safely treated with methotrexate. We review the literature on HIV-related CD8+ pseudolymphoma and the use of methotrexate in HIV-positive patients.

Acrodermatitis chronica atrophicans with pseudolymphomatous infiltrates.

In this study, we describe the clinicopathologic features of pseudolymphomatous infiltrates found within lesions of acrodermatitis chronica atrophicans (ACA). We studied 11 patients (10 females, 1 male, age range 60-88 years). The diagnosis of ACA in all cases was confirmed by clinicopathologic correlation and positive serology for Borrelia. Histopathologic examination revealed prominent, pseudolymphomatous inflammatory cell infiltrates in all cases, with 2 distinct patterns. Eight of 11 cases showed a band-like lymphocytic infiltrate, exocytosis of lymphocytes and a fibrotic papillary dermis, similar to features seen in mycosis fungoides. The other 3 cases showed dense, nodular-diffuse dermal infiltrates with many plasma cells and without germinal centers. The plasma cells expressed both kappa and lambda immunoglobulin light chains with a polyclonal pattern in all 3 cases. In conclusion, ACA may present with pseudolymphomatous infiltrates showing both a T-cell and, less frequently, a B-cell pattern. These lesions need to be distinguished from a cutaneous lymphoma. In the context of the knowledge of Borrelia-associated cutaneous lymphomas, follow-up seems advisable in these cases.

CD30+ lymphomatoid drug reactions.

We report 5 cases of cutaneous CD30+ lymphomatoid drug reactions that occurred shortly after the onset of drug exposure and resolved promptly upon withdrawal of the offending agents. The cases showed protean dermatologic manifestations ranging from diffuse erythema with desquamation to macules, papules, and annular plaques. The suspect drugs were amlodipine (a calcium channel blocker) for 2 cases, sertraline (a selective serotonin reuptake inhibitor) for 1 case, gabapentin for 1 case, and levofloxacin (a fluoroquinolone) versus cefepime (a fourth generation cephalosporin), and metoprolol (a beta blocker), in the fifth case. The histopathologic findings included varying combinations of spongiotic dermatitis, lichenoid infiltrates, and interface dermatitis with a dermal infiltrate of large atypical lymphocytes. Three of the 5 cases contained as much as 30% CD30+ staining of all lymphocytes, whereas the remaining 2 showed 5%-15% positivity. Three patients had a history of allergy or immune dysregulation. Increased knowledge of CD30 positivity in lymphomatoid drug reactions may be relevant in an era of targeted drug therapies. Recognition of these findings may help clinicians to tailor appropriate clinical evaluation and treatment including a review of medications and the removal of possible offending agents.

Granuloma annulare with prominent lymphoid infiltrates ("pseudolymphomatous" granuloma annulare).

Granuloma annulare (GA) is characterized histopathologically by 3 patterns: necrobiotic granuloma, interstitial incomplete form and, rarely, sarcoidal or tuberculoid granuloma. The amount of lymphoid infiltrate in GA is usually limited. We describe 10 cases of GA with prominent "pseudolymphomatous" lymphoid infiltrates mimicking cutaneous lymphoid hyperplasia. Patients were 6 males and 4 females (mean age 49.9 years, median age 47 years, age range 25-70). Lesions were localized to a limited area of the body (n = 6), or involved the entire trunk (n = 3), or were generalized (n = 1). The correct clinical diagnosis of GA was provided only in 30% of the cases. In all cases, histopathologic features were characterized by dense, nodular, superficial, and deep infiltrates of lymphocytes. Immunohistology revealed predominance of T lymphocytes in 7 of 7 tested cases. This "pseudolymphomatous" variant of GA represents a pitfall in the histopathologic diagnosis of the disease and may be misinterpreted as other types of cutaneous lymphoproliferative disorders.