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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., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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.

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.

Aluminium hydroxide is a well-known adjuvant used in vaccines. Although it can enhance an adaptive immune response to a co-administered antigen, it causes adverse effects, including macrophagic myofasciitis (MMF), subcutaneous pseudolymphoma, and drug hypersensitivity. The object of this study is to demonstrate pediatric cases of aluminium hydroxide-induced diseases focusing on its rarity, under-recognition, and distinctive pathology. Seven child patients with biopsy-proven MMF were retrieved from the Seoul National University Hospital (SNUH) pathology archives from 2015 to 2019. The medical records and immunisation history were reviewed, and a full pathological muscle examination was carried out. The mean age was 1.7 years (8.9-40 months), who had records of vaccination against hepatitis B, hepatitis A, and tetanus toxoid on the quadriceps muscle. The chief complaints were muscle weakness (n = 6), delayed motor milestones (n = 6), instability, dysarthria, and involuntary movement (n = 1), swallowing difficulty (n = 1), high myopia (n = 1), and palpable subcutaneous nodules with skin papules (n = 1). Muscle biopsy showed MMF (n = 6) and pseudolymphoma (n = 1) with pathognomic basophilic large macrophage infiltration, which had distinctive spiculated inclusions on electron microscopy. The intracytoplasmic aluminium was positive for PAS and Morin stains. Distinctive pathology and ultrastructure suggested an association with aluminium hydroxide-containing vaccines. To avoid misdiagnosis and mistreatment, we must further investigate this uncommon condition, and pharmaceutical companies should attempt to formulate better adjuvants that do not cause such adverse effects.

A 39-year-old Japanese woman presented with a pruritic infiltrated erythematous plaque on the right cheek. Histopathologic analysis of the erythema showed dermal edema, separation of collagen bundles, and nodular perivascular and periadnexal infiltration of lymphocytes in the whole dermis, without epidermal changes. Alcian blue staining intensity was elevated between the collagen bundles, indicating dermal mucinosis. The nodular infiltrates consisted of CD3+ T cell clusters and CD20+ B cell clusters (ratio, approximately 3:1) and included numerous CD123+ cells, indicative of plasmacytoid dendritic cells. Blood analysis revealed serum antinuclear antibody at a titer of 1:160 (homogeneous, speckled pattern). Lupus erythematosus tumidus with pseudolymphomatous infiltrates was diagnosed. Hydroxychloroquine treatment partially improved symptoms; however, the addition of prednisolone was required for complete resolution. Lupus erythematosus tumidus is sometimes accompanied by pseudolymphomatous infiltrates. Dermal mucinosis and the presence of numerous plasmacytoid dendritic cells are useful in differentiating lupus erythematosus tumidus from pseudolymphoma.

Purpose: : To present histopathological and immunohistochemical analysis of idiopathic inflammatory diseases of orbit and ocular adnexa., Methods: Design- A retrospective laboratory-based study. The study was carried out in an ocular pathology laboratory in a tertiary institute of northeast India where analysis of 93 cases was done in 5 years, during the period from 2011 to 2016. Hematoxylin--eosin and special stains were done for the diagnoses. Immunohistochemistry (IHC) panel was also carried out. For infectious pathology, Grocott's methenamine silver (GMS) stain for fungus, tissue Gram's stain for bacteria's, and acid-fast stains for tubercular bacilli were done. IHC panels were done for CD 20 (B-cells), CD-3 (T-cells), CD-45 (Leukocyte common antigen, LCA), BCL-2, CD-138 (Plasma cells), Kappa, Lambda, IgG-4 in tissue, IgG-4 in serum, etc. IHCs were done using kit methods (standardized) and adequate controls were taken for each sample., Results: 93 cases of nonspecific orbital inflammation were reported out of 1,467 specimens. Orbital pseudotumors (idiopathic orbital inflammatory disease, IOID) were seen in 27 cases (sclerosing variety-6); benign lymphoid hyperplasia in two cases; reactive lymphoid hyperplasia in 10 cases; atypical plasma lymphoproliferative reactive (polyclonal immunophenotypically, IgG4 negative) lesions in four cases; IgG-4 related disease in one case; nonspecific inflammatory reactions (conjunctiva, sclera, and lid) in 49 cases. In all the diagnoses, infections and lymphomas were excluded., Conclusion: Biopsy supported study on nonspecific orbital inflammation was important to know the pattern., Competing Interests: None

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., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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 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.

Pulmonary nodular lymphoid hyperplasia (PNLH) may show heavy lymphoplasmacytic infiltrates with increased immunoglobulin G4 (IgG4)-positive plasma cells as in IgG4-related disease (IgG4-RD). However, it is unclear whether PNLH could be a manifestation of IgG4-RD. A recent study reported the presence of Epstein-Barr virus (EBV) in IgG4-related lymphadenopathy. We postulated that a subset of PNLH might represent IgG4-related lung disease with EBV-positive lymphocytes as has been reported in IgG4-related lymphadenopathy. IgG and IgG4 immunohistochemistries were performed on 26 PNLH cases in our files (1994-2014) and on 9 controls including diffuse lymphoid hyperplasia of the lung without nodularity (n=2), usual interstitial pneumonia with increased lymphoplasmacytic infiltrates (n=5), and thoracic lymphadenopathy (n=2). EBV in situ hybridization was performed in the cases with the highest IgG4+ count (n=15). Median IgG4+ plasma cell count in PNLH was 36 cells per high-power field (interquartile range, 7-65) with median IgG4+/IgG+ ratio of 0.24 (interquartile range, 0.12-0.37). Three of 26 cases had a markedly increased IgG4+ count (range, 55-139) and IgG4+/IgG+ ratio (>0.4). Serum IgG4 level available in 1 of these cases was not elevated, and all 3 patients had alternate medical diagnoses. Absolute counts of IgG4+ plasma cells in PNLH did not significantly differ from the other control groups. Result of EBV in situ hybridization was negative in all cases tested. In conclusion, most PNLH cases had low IgG4+ cells, and there was no clinical evidence of IgG4-RD or EBV among those with increased IgG4+ cells., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Lymphocytic interstitial pneumonia (LIP) is a rare lung disease on the spectrum of benign pulmonary lymphoproliferative disorders. LIP is frequently associated with connective tissue diseases or infections. Idiopathic LIP is rare; every attempt must be made to diagnose underlying conditions when LIP is diagnosed. Computed tomography of the chest in patients with LIP may reveal ground-glass opacities, centrilobular and subpleural nodules, and randomly distributed thin-walled cysts. Demonstrating polyclonality with immunohistochemistry is the key to differentiating LIP from lymphoma. The 5-year mortality remains between 33% and 50% and is likely to vary based on the underlying disease process., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The aim of this study was to investigate demographic features, clinical characteristics, laboratory findings and posttreatment course of the disease in children with borrelial lymphocytoma (BL)., Methods: Between 2008 and 2014, we prospectively studied 33 children younger than 15 years with untreated BL. Data on demographic and clinical features were collected by means of a questionnaire. Serological testing and Lyme borrelia blood cultures were performed. All patients were treated with recommended antibiotics. Patients were followed up at least 3 months after inclusion into the study., Results: Twenty-two boys and 11 girls, aged 2-13 (median, 5.5) years, fulfilled the inclusion criteria. A tick bite at the site of BL was recalled by 30%. The median incubation period was 10.5 (range, 1-38) days. The median duration of BL before the initial examination was 10 (range, 0-270) days. In 88% of patients, BL was localized on ear lobe. The color/shape of BL was more often red (73%) and puffy (91%). Median size was 1.5 (range, 0.5-3) cm. The initial disease was mild in 82%. Associated symptoms were reported in 36% of patients. Concomitant solitary erythema migrans and meningitis were detected in 9% and 3% of patients, respectively. Serum borrelial antibodies were present in 40% of patients. In 7%, Borrelia afzelii was isolated from blood. Posttreatment course of the disease revealed the median duration of BL and systemic symptoms for 16 (range, 2-46) and 15 (range, 3-40) days, respectively., Conclusions: BL in children, treated with recommended antibiotics, is a mild disease with a good prognosis.

Progressively transformed germinal centers (PTGC), a lymph node process unfamiliar to most otolaryngologists, is a morphological variant of reactive lymphofollicular hyperplasia of lymph nodes. Immunoglobulin (Ig)G4-related disease (IgG4-RD) is a newly identified condition, characterized by hyper-IgG4-γ-globulinemia and mass-forming or hypertrophic lesions associated with infiltration of IgG4(+) plasma cells in the affected organs. Recently, a case study of PTGC was reported that fulfilled the diagnostic criteria of IgG4-RD (IgG4(+) PTGC) [1]. A 68-year-old male was referred to our hospital with swelling in the left submandibular region. Palpation revealed swollen lymph nodes, the largest of which measured 5cm in diameter. (18)F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography identified lymphadenopathy with high (18)F-FDG uptake in the left submandibular region. We strongly suspected malignant lymphoma, and excisional biopsy of the submandibular lymph node was performed under general anesthesia. Pathological findings were consistent with IgG4(+) PTGC, and serological examination demonstrated elevated levels of IgG4. These findings were consistent with IgG4-RD. The patient did not have systemic lesions; therefore, he has not undergone corticosteroid therapy. IgG4(+) PTGC should be considered as a differential diagnosis for cervical lymphadenopathy by otolaryngologists as well as pathologists., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Reactive lymphoid hyperplasia is a rare disease that forms a mass-like lesion and is characterized by the proliferation of non-neoplastic, polyclonal lymphocytes forming follicles. We recently encountered 2 cases of reactive lymphoid hyperplasia of liver, both of which were asymptomatic and mimicked hepatocellular carcinoma by various imaging modalities. Based on the clinical impression of hepatocellular carcinoma, surgical resections were performed. Microscopic findings revealed that both lesions consisted of an aggregation of lymphocytes consisting of predominantly B-cells, with multiple lymphoid follicles positive for CD10 and negative for bcl-2, consistent with the diagnosis of reactive lymphoid hyperplasia. Polyclonality of both lesions was further confirmed by B cell receptor gene rearrangement study. The incidence of reactive lymphoid hyperplasia in the liver is exceedingly rare, and it is difficult to differentiate such lesions from hepatic malignancies based upon clinical grounds. The clinicopathological findings and literature review of this report may be helpful to improve the clinical decision-making.

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., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Aim: To determine the proportion of idiopathic orbital inflammation (IOI) and orbital benign lymphoid hyperplasia (OBLH) accounted for by immunoglobulin (Ig)G4-related orbital disease (IgG4-ROD) using the comprehensive diagnostic criteria for IgG4-related disease published by Umehara et al and the consensus diagnostic criteria published by Deshpande et al. Secondary aims were to compare the histological and clinical features of IgG4-ROD and non-IgG4-ROD cases, and to compare IgG4-ROD cases diagnosed using the comprehensive diagnostic criteria with those diagnosed using the consensus diagnostic criteria., Methods: A retrospective histopathological review and clinical case series. 55 cases of biopsy-confirmed non-granulomatous IOI and 10 cases of biopsy-confirmed OBLH were included. The intensity of sclerosis, lymphoplasmacytic infiltration and eosinophilic infiltration was graded from 0 to 3+ using a standardised and validated scoring system., Results: IgG4-ROD accounted for 50% and 40% of cases originally diagnosed as OBLH and 23.6% and 5.4% of cases originally diagnosed as IOI, using the comprehensive diagnostic criteria and the consensus diagnostic criteria, respectively. IgG4-ROD cases had numerous significant histological differences, but relatively few significant clinical differences, from non-IgG4-ROD cases. Compared with the comprehensive diagnostic criteria, the consensus diagnostic criteria identified a group of IgG4-ROD cases with a slightly higher ratio of IgG4+ to IgG+ (p=0.01) and a slightly longer duration of symptoms (p=0.02)., Conclusions: This is the largest review of IgG4 staining among biopsy-confirmed IOI and OBLH. IgG4-ROD accounted for a substantial proportion of OBLH. The prevalence among cases of IOI was considerably reduced when the consensus diagnostic criteria were used in place of the comprehensive diagnostic criteria., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

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., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Allergic reactions occurring after tattooing, especially after the use of red tattoo ink ingredients are relatively rare. We report a painful skin reaction occurring 6 months after the tattoing of the right lower extremity in a 30-year-old female patient. Pathohistological and immunchemical results confirmed a pseudolymphoma. Only the tangential excision of the affected areas led to a sufficient healing process. Split thickness skin grafts were used for defect coverage. 2 years later, the patient was still pain free and the wounds had healed completely without any irritation., (© Georg Thieme Verlag KG Stuttgart · New York.)

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)., (© 2014 British Association of Dermatologists.)

Mycosis fungoides is the most common primary cutaneous lymphoma; however, it remains a significant diagnostic challenge, in part because of the overlap with several inflammatory dermatoses. Despite advances in immunohistochemistry and molecular diagnostics, false-positive, false-negative, and indeterminate diagnoses are not uncommon. In most cases, the overall balance of morphologic, immunophenotypic, and genetic features must be considered carefully because there are few sensitive and specific clues to the diagnosis. Moreover, an appropriate clinical presentation is essential to the diagnosis and helps to favor or exclude inflammatory/reactive processes. Herein, we discuss 3 important inflammatory dermatoses that may closely simulate mycosis fungoides, and we review the use of ancillary studies in these challenging cases.

Small endoscopic biopsies of the terminal ileum may be difficult to assess for early involvement by lymphoma. Immunophenotypic and genotypic analyses are often utilized, but the performance of these studies in this setting is not well defined. Terminal ileal biopsies from 66 patients with prominent lymphoid hyperplasia and abnormal "lymphoma-like" morphology were evaluated by immunohistochemistry (IHC) for CD3, CD5, CD43, CD20, CD21, and CD10 expression and for IGH@ gene rearrangement by polymerase chain reaction using BIOMED-2 primers. Patients ranged in age from 3 to 80 years. Indications for endoscopy included inflammatory bowel disease (29), diarrhea and/or abdominal pain (28), history of lymphoma (13), and others (4). Four biopsies with abnormal morphology had abnormal IHC and a clonal IGH@ peak; all were obtained from patients with a history of lymphoma and determined to be recurrent lymphoma. Three biopsies with abnormal morphology and abnormal IHC but no clonal IGH@ peak were obtained from patients with a history of lymphoma (2) and chronic diarrhea (1); all showed symptom resolution or remission of disease (mean follow-up, 37 mo). Eight biopsies with abnormal morphology but no abnormal IHC expression also had abnormal IGH@ results (4 clonal and 4 borderline). IGH@ evaluation of follow-up biopsies for these cases were nonclonal (7) or clonal, but with a different clone from the prior biopsy (1); follow-up of the 8 patients showed no evidence of lymphoma (mean, 37.8 mo). Abnormal IHC expression pattern or clonal IGH@ rearrangement in endoscopic biopsies of the lymphoid-rich terminal ileum do not necessarily warrant a diagnosis of lymphoma. To prevent misdiagnosis, B-cell clonality studies should only be performed when there is strong clinical suspicion for lymphoma and compelling IHC data; the absence of a reproducible clone in repeat biopsy specimens may be useful in patients that do not have other clinical evidence of lymphoma.

Initial reports emphasized the immunophenotypic similarities between benign and malignant T cell populations, while some previous studies indicating that aberrant T-cell antigen loss is a good marker for detecting malignant T-cell proliferation. Recently, we found a very interesting and thought-provoking phenomenon: In benign disease-28 of 38 (73.7%) cases of Kikuchi's disease also showed aberrant phenotypes with loss of pan-T cell antigens, which makes the differential diagnosis between Kikuchi's disease and T cell lymphoma more challenging. In our study, 38 cases of Kikuchi's disease and 30 cases of reactive lymphoid hyperplasia (RLH) were studied by EliVision immunohistochemical staining. As well as TCR gene rearrangement using PCR was negative in 10 tested cases of the Kikuchi's disease. Among these cases, the most common antigen deficiency was CD5 (22 cases), then CD7 (11 cases), CD2 (8 cases) and CD3 (2 cases). Compared with proliferative and xanthomatous types of Kikuchi's disease, antigens tended to be lost in necrotizing type. Based on follow-up data, a correlation was not found between the occurrence of aberrant phenotypes and prognosis. In RLH, obvious pan-T cell antigen loss was also not found. In conclusion, this is the first study to demonstrate distinct patterns of antigen loss in Kikuchi's disease, suggesting that T cell antigen loss is not reliable as an auxiliary diagnostic standard for T cell lymphoma.

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.

Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized disease characterized by elevated serum IgG4 levels, tissue infiltration rich in IgG4(+) plasma cells. We report on a case which was first considered as pseudolymphoma from the histopathological analysis, but finally diagnosed as IgG4-related skin lesions. As the morphological features of cutaneous involvement of IgG4-RD are consistent with those of cutaneous pseudolymphoma, we tried immunostaining past potential cases of IgG4-RD. Thirty-two skin specimens (15 men and 17 women; mean age, 53 years) diagnosed as having pseudolymphoma were retrieved from the archives to conduct hematoxylin-eosin, IgG and IgG4 staining. Out of the 32 cases of cutaneous pseudolymphoma, germinal center formation was seen in 22 cases, and moderate-severe fibrosis was seen in seven cases. Eleven cases showed more than 10 IgG4(+) plasma cell infiltration/high-power field, and among these 11 cases, seven cases (22%) showed A ratio of IgG4(+)/IgG(+) cells of more than 40%. Thus, out of the 32 cases of cutaneous pseudolymphomas, two cases (6.3%) satisfied IgG4-RD histopathological diagnostic criteria. As clinical presentations and histopathological features of skin involvement of IgG4-RD are analogous to cutaneous B-cell pseudolymphoma, careful identification is required through systemic examination, serum IgG4 measurement and other means., (© 2013 Japanese Dermatological Association.)

On the basis of an initial case, we hypothesized that IgG4-positive plasma cells may be increased in pulmonary nodular lymphoid hyperplasia (PNLH) compared with other lymphoid proliferations of the lung. Six cases of PNLH, 9 cases of low-grade B-cell lymphoma of the bronchus-associated lymphoid tissue (BALT), 8 cases of intraparenchymal lymph nodes, 8 cases of either primary or secondary follicular bronchiolitis, and 4 cases of lymphocytic interstitial pneumonitis were stained by immunohistochemical analysis for IgG4 and IgG. The mean number of IgG4-positive and IgG-positive plasma cells and the IgG4/IgG ratio were determined from a manual count of images from 3 separate high-power fields (hpf) of areas showing the highest numbers of stained cells, respectively. The mean number of IgG4-positive plasma cells and the IgG4/IgG ratio were significantly increased in PNLH (IgG4=78/hpf, IgG4/IgG=0.35) compared to low-grade lymphoma of BALT (IgG4=4/hpf, P=0.02; IgG4/IgG=0.03, P=0.005), intraparenchymal lymph nodes (IgG4=7/hpf, P=0.03; IgG4/IgG=0.06, P=0.007), follicular bronchiolitis (IgG4=0/hpf, P=0.02; IgG4/IgG=0, P=0.004), and lymphocytic interstitial pneumonitis (IgG4=2/hpf, P=0.02; IgG4/IgG=0.06, P=0.007). These findings support our current understanding of PNLH as a distinct form of reactive lymphoid proliferation, potentially aid in its distinction from low-grade B-cell lymphoma of BALT, and raise the possibility that PNLH may belong within the family of IgG4-related sclerosing diseases.

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.

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.

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., (Copyright © 2013 S. Karger AG, Basel.)

The term pseudolymphoma refers to a heterogeneous group of benign reactive T-cell or B-cell lymphoproliferative processes of diverse causes that simulate lymphoma clinically and histologically but usually undergo spontaneous remission. Its pathogenesis is still unclear. The prognosis is good although some evidence suggests that pseudolymphoma may progress to lymphoma. Pseudolymphoma of the urinary tract is extremely rare. We herein report a case of pseudolymphoma of the renal sinus in a 70-year-old man, associated with a high grade urothelial carcinoma of the bladder and to a prostatic adenocarcinoma (Gleason score 6). A brief review of the literature is included. The kidney showed a well-defined, whitish soft mass which involved the renal sinus. Microscopically, the lesion of the renal sinus consisted of a proliferation of small to medium size lymphocytes (CD20 positive and Bcl-2 negative) sometimes arranged in hyperplastic follicular structures. The diagnosis was confirmed by molecular studies which showed an oligopolyclonal IgH rearrangement. To the best of our knowledge, this is the second case of pseudolymphoma with a complete molecular characterization ever described in the renal sinus and the first one associated with multiple urogenital carcinomas.

Aims: The cutaneous manifestation of IgG(4)-related disease has rarely been reported. The aim of this study is to identify and describe the cutaneous manifestations associated with IgG(4)-positive plasma cell infiltration in the skin., Methods: The authors investigated two cases of IgG(4)-related disease with solitary skin lesions and compared the immunohistochemical characteristics of infiltrating cells among IgG(4)-related disease, Kimura's disease and cutaneous pseudolymphoma., Results: IgG(4)-related disease manifested as an indurated plaque on the anterior chest in one case and a nodule on the toe in the other case. Histopathologically, skin lesions of IgG(4)-related disease showed a dense, mixed-cell infiltrate containing lymphocytes, plasma cells and eosinophils along with fibrosis. Plasma cells stained positively with anti-IgG and anti-IgG(4) antibodies, and the ratio of IgG(4)+/IgG+ cells was more than 50%. Serum levels of IgG and IgG(4) were not elevated and no lesions were found in other organs. Skin samples taken from Kimura's disease showed histopathological features similar to those of IgG(4)-related disease. The proportion of IgG(4)+/IgG+ was high in Kimura's disease, but not in cutaneous pseudolymphoma., Conclusions: The solitary skin lesions of IgG(4)-related disease were similar histologically and immunohistochemically to the skin lesions of Kimura's disease. The concept of IgG(4)-related disease may help clarify the pathomechanism of diseases of unknown aetiology that possess features of IgG(4)-related disease.

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.

The diagnosis of B-cell lymphoma (BCL) is often dependent on the detection of clonal immunoglobulin (Ig) light chain expression. In some BCLs, the determination of clonality based on Ig light chain restriction may be difficult. The aim of our study was to assess the utility of flow cytometric analysis of surface Ig heavy chain (HC) expression in lymphoid tissues in distinguishing lymphoid hyperplasias from BCLs, and also differentiating various BCL subtypes. HC expression on B-cells varied among different types of hyperplasias. In follicular hyperplasia, IgM and IgD expression was high in mantle cells while germinal center cells showed poor HC expression. In other hyperplasias, B cell compartments were blurred but generally showed high IgD and IgM expression. Compared to hyperplasias, BCLs varied in IgM expression. Small lymphocytic lymphomas had lower IgM expression than mantle cell lymphomas. Of importance, IgD expression was significantly lower in BCLs than in hyperplasias, a finding that can be useful in differentiating lymphoma from reactive processes.

Objective: To study the possible loss of pan-T cell antigens CD2, CD3, CD5 and CD7 in Kikuchi's disease and to evaluate the role of T cell antigen loss in distinguishing benign from malignant T-cell lymphoid lesions., Methods: Formalin-fixed and paraffin-embedded tissues of 33 cases of Kikuchi's disease and 15 cases of reactive lymphoid hyperplasia were studied by EliVision immunohistochemical staining for CD2, CD3, CD5 and CD7., Results: Twenty-four of the 33 (72.7%) cases of Kikuchi's disease lost one or more of the pan-T cell antigens, including the loss of CD5 only (13 cases), CD7 only (1 case), CD2 only (1 case), CD2 and CD7 (2 cases), CD5 and CD7 (4 cases), CD2 and CD5 (2 cases), and CD2, CD7 and CD5 (1 case). Amongst these cases, the commonest antigen loss was CD5 (20 cases, 60.6%), followed by CD7 (8 cases, 24.2%) and CD2 (6 cases, 18.2%). Compared with the xanthomatous subtype of Kikuchi's disease, the loss of antigens was more commonly seen in the proliferative and necrotizing subtypes. Analysis of follow-up data showed that the loss of antigens in Kikuchi's disease was not significantly associated with the prognosis. In reactive lymphoid hyperplasia, the expression of CD2, CD3, CD5 and CD7 was seen in all cases with similar intensity, with no obvious pan-T cell antigen loss., Conclusion: Loss of one or more pan-T cell antigens in Kikuchi's disease is demonstrated in present study, suggesting that the immunophenotypic pattern is not unique in T cell lymphoma.