Search

Importance: Reactions to tattoo may simulate common dermatosis or skin neoplasms. Histopathology allows diagnosis and helps determining the level and degree of inflammation associated, consequently orientating treatment., Objective: To describe the histological features found in biopsies of cutaneous reactions to tattoo., Design: This study was designed as a multicenter case series., Setting: All consecutive histopathological samples of tattoos referred from 1992 to 2019 to the Hospital General de Catalunya, Hospital Germans Trias i Pujol, and a private practice, all in Barcelona, Spain, and from the Kempf und Pfaltz Histologische Diagnostik in Zurich, Switzerland were retrieved from the files., Participants and Exposure: The inclusion criteria were all cosmetic/permanent makeup, artistic/professional, and traumatic tattoos associated with either inflammatory reactions alone and/or with tumors and/or infections. Exclusion criteria were cases without any associated pathologic finding in the place of the ink, amalgam tattoos, and medical or temporary tattoos., Main Outcomes and Measures: In all patients, clinical features (age, sex, location, tattoo color, and presentation) were recorded. Histological features evaluated included ink color, associated tumors or infections, and inflammatory reaction pattern. Inflammation was graded in low to moderate or severe., Results: From 477 biopsies diagnosed as tattoos, 230 cases from 226 patients met the inclusion criteria. Samples corresponded to 107 male and 120 female subjects and 3 of unknown gender. Median age was 39 years (ranging from 9 to 84 years). Fifty-three samples were referred from centers in Spain and 177 from the center in Switzerland. The series was analyzed in 2 parts: tattoos associated only with inflammatory reactions (117/230) and tattoos associated with tumors or infections (113/230). The most common form of inflammatory pattern associated with tattoo was the fibrosing reaction (79/117, 68%), followed by granulomatous reaction (56/117, 48%), lichenoid reaction (33/117, 28%), epithelial hyperplasia (28/117, 24%), pseudolymphoma (27/117, 23%) and spongiotic reaction (27/117, 23%). Combined features of 2 or more types of inflammatory patterns were seen in 64% cases., Conclusions and Relevance: Our series confirms that cutaneous reactions to tattoos are polymorphous. Inflammation tends to present with combined patterns. Infections are tending to decline, and pathologic findings are not specific to ink color or clinical features., Competing Interests: Dr. Fernández-Figueras has disclosed that she was a consultant/adviser to Almirall. Lippincott CME Institute has identified and resolved all conflicts of interest concerning this educational activity., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Primary cutaneous lymphomas (PCLs) and pseudolymphomas presenting as single pink-red nodules/tumors are highly unspecific and include a wide differential diagnosis., Objective: To describe the dermoscopic characteristics of PCL/pseudolymphoma., Methods: In this retrospective, case-control study, we evaluated the dermoscopic features of patients with solitary PCL/pseudolymphoma tumors and compared them to a control group of non-lymphomatous, nonpigmented, solitary tumors (e.g., basal cell carcinoma, amelanotic melanoma, etc)., Results: We included 14 patients with PCL/pseudolymphomas and 35 controls. T-cell and B-cell lymphoma proportions were 28.6% (n = 4) and 71.4% (n = 10), respectively. Compared to controls, most lymphomas presented dermoscopically with orange color (71.4% vs. 14.2%, P < 0.001), follicular plugs (85% vs. 2.8%, P < 0.001), and as  organized lesions (85% vs. 31.4%, P = 0.001). Coexistence of orange color and follicular plugs had an odds ratio (OR) of 2.8 (P < 0.001), highly suggestive of PCL . The kappa index for independent observers was 0.66, 0.49, 0.43 for orange background, follicular plugs, and organized lesion, respectively. Histopathologic correlation was performed in six PCL cases and showed dense diffuse and perifollicular lymphocytic infiltrate in all cases and keratin plugs in five of six cases, possibly correlating with the orange color and the follicular plugs, respectively., Conclusion: Primary cutaneous lymphomas/pseudolymphomas present with characteristic dermoscopic findings irrespective of immunohistochemical subtype., (© 2019 The International Society of Dermatology.)

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.)

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.

Context: Primary cutaneous CD4⁺ small/medium T-cell lymphoma is a provisional and controversial entity with a broad differential diagnosis. Despite being an uncommon lymphoma, it is a frequent diagnostic consideration in cutaneous biopsies with a dense lymphoid infiltrate because it shows overlapping features with reactive lymphoid hyperplasia (pseudolymphoma) and a variety of other primary cutaneous and systemic lymphomas. However, proper classification of this process is important for determining patient prognosis and treatment options., Objective: To review the clinical, morphologic, immunophenotypic, and genetic features of primary cutaneous CD4⁺ small/medium T-cell lymphoma and contrast those features with entities in the differential diagnosis., Data Sources: Applicable literature will be reviewed with emphasis on current controversies and distinguishing characteristics., Conclusions: Although many consider primary cutaneous CD4⁺ small/medium T-cell lymphoma to be indistinguishable from reactive lymphoid hyperplasia/pseudolymphoma, it can be differentiated from other primary cutaneous and systemic lymphomas. Patients with solitary lesions of primary cutaneous CD4⁺ small/medium T-cell lymphoma generally have an excellent prognosis. Nevertheless, a subset of patients who have been reported to meet criteria for this lymphoma have followed a more-aggressive course; however, those patients show some differing clinical, morphologic, and immunophenotypic features.

Skin is the main sufferer of the adverse drug reactions (ADRs), being involved in 30% of all ADRs cases. However, ADRs are generally underestimated because of the difficulty to correlate the event to a particular drug. A careful anamnestic history is crucial to establish the causal link between an ADR and the specific drug. Clinical, developmental and medical history is important to define an ADR but sometimes you need to make histological examination to get additional diagnostic indications. However, the histological findings observed during the ADRs are hardly or not easily distinguishable from other skin diseases. Furthermore, the patient is often administered multiple drugs, so that the evaluation of histological findings is a complex one. In the present work we have reviewed the most frequently reported histological pictures induced by drugs as associated with a specific ADR, following, as criterion, the localization of the damage within the skin. So ADRs are divided into reactions in which the damage is localized in the epidermis, at dermal-epidermal (junction) level, in the dermis, subcutaneous fat and adnexal structures. We then briefly describe the clinical and histological pictures most frequently observed in ADRs.

The immune system protects our organism and, of course, our skin from harmful factors. One of the key elements of the immune system is lymphocytes. Lymphocytes play a role in the pathogenesis of various skin diseases. Lymphocytic infiltrates are seen in many skin diseases. Some of the skin diseases characterized by lymphocytic infiltration show up in specific anatomic locations, whereas other entities can be placed in all areas of the body. The course of lymphocytic infiltrations of the face is variable and unpredictable, most often lasting from months to years. The most important diseases with lymphocytic infiltration of the face are pseudolymphomas. This review discusses various types of cutaneous pseudolymphomas and other diseases with lymphocytic infiltration mainly involving the face., (© 2013 Elsevier Inc. All rights reserved.)

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.

Lymphoplasmacytic plaque in children has been proposed as a rare, emerging clinicopathologic entity characterized by solitary, extratruncal, asymptomatic papules and plaques that are typically found in healthy young Caucasian females. Biopsy of these lesions reveals a dermal lymphoplasmacytic infiltrate with or without epithelioid granulomas. Two unique patients with lymphoplasmacytic plaque in children are presented in this report, including a 26-month-old female with a lesion on her finger, who represents both the youngest described patient and the first documented with a finger lesion, as well as a 17-year-old young woman with a left thigh lesion, who represents the patient with the longest clinically and histopathologically observed lesion to date. These two additional patients corroborate the experience of lymphoplasmacytic plaque in children in the six previously reported cases and further expand the clinicopathologic spectrum of the disease. Recognition of lymphoplasmacytic plaque in children is important to facilitate distinction from potential differential considerations, including lymphoproliferative disorders and infectious conditions, particularly as the experience to date appears to suggest that lymphoplasmacytic plaque in children represent a reactive (pseudolymphomatous) condition., (Copyright © 2012 John Wiley & Sons A/S.)

The current report examines the evolution of the concepts of immunocytoma and pseudolymphoma in a historical perspective, paying special attention to their evolvement into the groups of marginal-zone lymphoma and cutaneous MALT-lymphoma. It also examines the current conception of the existence of at least two types of cutaneous MALT-lymphomas and their relation to the duality immunocytoma/pseudolymphoma from the old literature.

Disseminated miliarial-type lymphocytoma cutis is a rare clinicopathologic subtype of lymphocytoma, characterized by numerous translucent micropapules and located on the head and neck. We describe here the clinical, histological and immunological features of miliarial-type perifollicular B-cell pseudolymphoma in two women aged 32 and 49 years presenting with numerous 1-2 mm translucent papules on the head and neck. Microscopic examination revealed features typical of a miniature lymphocytoma cutis with a superficial nodular infiltrate housing small well-circumscribed germinal centers containing tingible body macrophages and surrounded by a distinct mantle zone. The immunohistological profile was also typical of lymphocytoma cutis, and polymerase chain reaction analysis of the IgH gene rearrangement did not show any clonal B-cell population. The lesions resolved spontaneously in one case and improved after treatment with hydroxychloroquine in the second patient. The presentation of this subtype of lymphocytoma is a formidable clinical diagnostic challenge. Rosacea, sarcoidosis, democidiosis, lupus miliaris disseminatus faciei and steroid acne are easy to exclude on the basis of histological profile. However, the miliarial form of primary cutaneous center lymphoma is difficult to rule out. Dermatologists and dermatopathologists should be aware of this unusual form of lymphocytoma cutis, which can be misleading during clinical diagnosis., (Copyright © 2012 John Wiley & Sons A/S.)

IgG4-related sclerosing disease is a syndrome characterized by the involvement of a wide variety of tissues by lymphoplasmacytic infiltrates and sclerosis, elevated serum IgG4 titer, and increased IgG4+ plasma cells in tissues. This report describes 2 cases with skin involvement, a feature not well documented in the literature. The patients had plaques or nodules in the skin of the cheek, temporal or periauricular region. Histologically, there was dermal and subcutaneous involvement by a nodular lymphoid infiltration often interspersed with lymphoid follicles and sclerotic stroma. The infiltrate was rich in plasma cells, small lymphocytes, and sometimes plasmablasts. The IgG4+ cell count was high (342 to 425 per high power field), with an IgG4/IgG proportion from 68% to 100%. As the morphology was compatible with pseudolymphoma, 14 cases of cutaneous pseudolymphoma were retrieved from the archives for IgG4 and IgG immunostaining. Two cases exhibited marked increase in IgG4+ cells, and showed many similarities with cutaneous manifestation of IgG4-related sclerosing disease, but the limited available clinical information precluded a conclusion on their nosologic nature. In summary, IgG4-related sclerosing disease can manifest with skin lesions, and is also one of the potential etiologies of cutaneous pseudolymphomas.

A 46-year-old man presented with a 1-year history of asymptomatic papules on the right arm, without an antecedent event. Initial clinical and histopathologic features were consistent with a pseudolymphoma without gene rearrangements, and the patient was treated with intralesional glucocorticoids. Four months later, the patient developed additional papules and plaques on the right arm, and, at this time, clinical and histopathologic features were most consistent with a T-cell-rich, large B-cell lymphoma, with monoclonal immunoglobulin light chain gene rearrangement. Systemic evaluation showed no evidence of extracutaneous involvement. The transformation of a pseudolymphoma into a large B-cell lymphoma is a rare event. This patient's subtype, diffuse large B-cell lymphoma-other, carries an intermediate prognosis when compared to the more aggressive leg subtype and more indolent folliculocentric subtype. Potential therapeutic options include local radiotherapy, chemotherapy, and rituximab.

Background: Debates regarding nosology and clonality surround the entity known as cutaneous pseudolymphoma and its questionable transformation to frank cutaneous lymphoma. The relevance of these arguments is important, not only from a diagnostic standpoint, but also for making inferences based upon behavior, prognosis, and treatment., Objective: Our goal was to demonstrate further evidence of progression from cutaneous pseudolymphoma to malignant lymphoma while at the same time advocating a comprehensive plan for evaluation, treatment, and followup of these patients., Methods: A retrospective review was conducted of four patients initially considered to have cutaneous B-cell pseudolymphoma (CBPL) and who were later treated for primary cutaneous B-cell lymphoma (CBCL). A review of the literature of cases suggesting progression to malignant lymphoma from precursor lesions was also performed., Results: Four patients initially diagnosed with CBPL by a combination of histologic, immunophenotypic, and gene rearrangement criteria had a progressive clinical course that, over a range of 17-51 months, evolved into CBCL. All patients had a comprehensive systemic workup to rule out the possibility of extracutaneous disease and were treated with local radiation therapy and close followup. There has been no evidence of extracutaneous disease with an average followup of 14 months., Conclusion: The potential for certain cutaneous pseudolymphomas to progress to CBCL is real. The combination of histologic and immunophenotypic criteria, along with the clinical picture, remains the best way to judge the aggressiveness of the lesion. Gene rearrangement studies, whether performed by Southern blot or polymerase chain reaction (PCR), are of limited value and should be used to support the overall clinicopathologic picture. Radiation therapy of these patients should be thought of early in the management plan and is a very successful form of treatment when combined with close followup.

Skin drug reactions are cutaneous rashes caused by drugs, through different pathogenic mechanisms that can be classified into two groups: immunologically mediated and non-immunologically mediated. In the first part of this chapter we are going to study the cutaneous reactions to aromatic antiepileptic drugs, namely phenytoin, and focusing attention towards potentially life-threatening drug reactions of an immune cause such as toxic epidermal necrolysis and hypersensitivity syndrome. Secondly we are going briefly summarize skin reactions to drugs usually dealt with in neurological diseases, following a classification based on the morphological aspects of the lesions present in each reaction.

Background: The cell production vs the cell loss rate in one of the most important parameters in evaluating growth and biological behavior of neoplasms. Individual cell disintegration in tissues, apoptosis, is a constant finding in various tumors and has been shown, by using several techniques, as a recognizable cell death that is different from necrosis., Design: We studied the apoptosis-proliferation ratio in various lymphoproliferative disorders in the skin, including mycosis fungoides (MF), cutaneous T-cell lymphoma showing solid tumor mass (CTCL), B-cell lymphoma of the skin (BCL), lymphomatoid papulosis (LyP), and cutaneous pseudolymphoma by using terminal deoxyuridine triphosphate (dUTP)-biotin nick end labeling (TUNEL), a newly developed method to detect internucleosomal breaks characteristic of apoptotic cells., Setting: University referral center., Patients: Fifty patients with cutaneous lymphoproliferative diseases., Main Outcome Measures: Proliferation indexes and apoptosis index calculated by using immunohistochemical techniques., Results: The proliferation indexes in pseudolymphoma, which were calculated by using immunohistochemical analyses with anti-proliferating cell nuclear antigen and anti-MIB-1 monoclonal antibodies, were significantly lower than the indexes of MF, CTCL, BCL, and LyP, whereas, the apoptosis index in Lyp was significantly higher than in any other lymphoproliferative diseases studied. The apoptosis-proliferation ratio in the tumor stage of MF, CTCL, and BCL was almost constant, but the ratios in LyP and the plaque stage of MF were significantly higher than in the other diseases studied., Conclusions: The clinical behavior of each lymphoproliferative disease in the skin seemed to be reflected in the apoptosis and proliferation indexes. We conclude that these indexes may become useful factors in the determination of the diagnosis and the prognosis for patients with lymphoproliferative diseases.