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.

Primary cutaneous lymphoproliferations in the gray zone between marginal zone lymphoma and CD4+ small/medium T-cell lymphoproliferative disease.

BACKGROUND: Primary cutaneous marginal zone lymphoma (PCMZL) and primary cutaneous CD4+ small/medium T-cell lymphoproliferative disease (CD4+ TLPD) are two distinct entities with excellent prognosis; however, they show profound clinical and histopathological similarities, leading to differential diagnostic uncertainty. AIMS: Our aim was to review and reanalyze cases of primary cutaneous lymphoproliferations diagnosed at Semmelweis University, featuring characteristics of PCMZL and CD4+ TLPD. MATERIALS AND METHODS: Cutaneous lymphoma biopsy specimens between 2018 and 2022 were collected and re-evaluated. Medical history, clinical picture, imaging, and laboratory findings were collected. Immunohistochemical staining for CD20, CD3, BCL6, CD10, PD1, CD3, CD4, CD8, and PCR tests for IGH, IGK, TCRB, and TCRG were repeated in selected cases. RESULTS: Among 55 cases diagnosed as PCMZL (16) or CD4+ TLPD (39), 3 patients had been diagnosed with both LPDs at different time points of their disease course. Four additional patients were identified with single lesions featuring overlapping histopathological characteristics of both LPDs and both monoclonal IGH and TCR rearrangements. All patients are currently in complete remission with local treatment. CONCLUSION: We propose that besides the overlapping histopathological, molecular, and clinical features, the subsequent appearance of PCMZL and CD4+ TLPD in a short timeframe in the same patients may suggest a common pathogenic background.

Lymphoplasmocytic plaque in children: A report of an atypical location.

Lymphoplasmocytic plaque in children (LPC) is a rare and distinctive skin disorder primarily affecting the pediatric population. Characterized by its unique histopathological features, the condition manifests as well-defined plaques with a predominance of lymphocytes and plasma cells infiltrating the dermis. Despite its limited prevalence, recognizing this entity is crucial for accurate diagnosis and appropriate management of affected patients. We report the case of a 10-year-old male presenting with LPC in the extensor surface of the upper arm, a rarely reported location, treated with both topical and intralesional corticosteroids resulting in partial improvement.

Features of tattoo-associated cutaneous lymphoid hyperplasia on reflectance confocal microscopy and line-field confocal optical coherence tomography.

The popularity of tattoos has led to an increase in associated skin reactions, including complications such as infection, allergic reactions and rare conditions such as tattoo-induced cutaneous lymphoid hyperplasia (CLH). CLH is a benign lymphoproliferative reaction with clinical features resembling malignant cutaneous lymphomas. Non-invasive diagnostic tools like reflectance confocal microscopy (RCM) and the new line-field confocal optical coherence tomography (LC-OCT) are being studied in dermatology better to understand the morphological patterns of many dermatological diseases. Between September 2021 and May 2023, patients with suspicious lesions for tattoo-related CLH were analysed using RCM and LC-OCT before confirming the diagnosis of CLH through skin biopsy and histopathological examination. The study included five cases of CLH. It focused on the analysis of high-quality LC-OCT images/videos and RCM images to investigate the features of CLH in tattooed individuals. Most (80%) cases exhibited a mixed T and B lymphocyte infiltration subtype, while 20% showed a predominant T infiltration subtype. RCM and LC-OCT revealed characteristic features, including architectural disarray, fibrosis, lymphoid infiltrates, and pigment deposits in the epidermis and dermis. Non-invasive tools such as RCM and LC-OCT are valuable in diagnosing tattoo-related CLH. While skin biopsy remains the current standard for diagnosis, RCM and LC-OCT can serve as helpful adjuncts in identifying the most representative area for biopsy. They may potentially become alternative diagnostic options in the future, offering benefits in terms of cost, diagnostic efficiency, aesthetics and patient satisfaction as the prevalence of tattoo-related adverse reactions continues to rise.

Drug-induced cutaneous pseudolymphoma: A systematic review of the literature.

Drug-induced cutaneous pseudolymphoma (CPL) is a common form of pseudolymphoma and there are numerous drugs associated with it. In this study, we performed a systematic review of the literature by searching PubMed/Medline and Embase databases to determine the most common drugs responsible for CPL and to define the demographic, clinical, histopathological and immunopathological characteristics of patients (updated on 30 December 2020). From 883 initially found articles, 56 studies (89 reported cases) were included. The mean age of patients was 54.4 ± 17.7 (ranging 8-86) years, and 46 (51.7%) were men. The median time interval between drug intake and CPL occurrence was 120 days (range 1-7300 days). The shortest median time interval between taking the drug and the onset of the disease was observed among patients taking antidepressants (60 days) (range 7-540) and the longest median time interval was observed in individuals using immunomodulators (300 days) (range 3-7300). The most-reported drug categories causing CPL were anti-hypertensives (17.9%), anticonvulsants (14.6%), monoclonal antibodies (13.4%) and antidepressants (11.2%). Moreover, the most common drugs were phenytoin (6.7%), amlodipine (5.6%), fluoxetine (5.6%) and carbamazepine (4.4%). Histopathological evaluation of 76 cases revealed 62 (81.5%) reports of T-cell infiltrations. Furthermore, positive reports of CD4 (94.0%), CD8 (93.0%) and CD30 (87.5%) were noted. The lowest prevalence of CD30-positive reports was observed among monoclonal antibodies. In conclusion, anti-hypertensives, anti-convulsants, monoclonal antibodies and anti-depressants are the most common drugs responsible for CPL. It mostly presents in middle-aged patients with almost no gender difference as pruritic papules, nodules and plaques.

Borrelial pseudolymphoma of the eyebrow in an adult.

Borrelial pseudolymphoma, more commonly known as Borrelia lymphocytoma and previously also as lymphadenosis benigna cutis, is a rare manifestation of Lyme borreliosis, which occurs nearly always in children after an infection caused by Borrelia afzelii; this pathogen is transmitted exclusively by the Ixodes ricinus tick in our region. The most common body locations of this lymphocytoma include the earlobe, scrotum, nipples and the areomamillary complex. Therefore, the case of our patient was unexpected and quite rare. The aim of this article is to point out the high incidence of Lyme disease and its atypical manifestations which can be cured without surgical intervention in most cases. The authors describe the case of a 58-year-old healthy female patient with a very rare manifestation of Lyme disease.

Cutaneous B cell lymphomas: standards in diagnostic and clinical work-up. Hints, pitfalls and recent advances.

This review focuses upon the pragmatic diagnostic approach of suspicious B cell infiltrations in the skin and lists the necessary histopathological and molecular tools for a thorough work-up. We start with the description of different histopathological patterns of cutaneous B cell infiltrations and recommend pattern-dependent immunohistochemical staining algorithms for further differential diagnosis. A summarised description of the current World Health Organisation (WHO) subtypes of primary cutaneous B cell lymphomas highlighting their most relevant clinical, histopathological and molecular features is included. Differential diagnostic clues towards secondary infiltrations by systemic B cell lymphomas, B cell-rich T cell lymphoproliferative disorders and pseudolymphomas are provided. Furthermore, the most important pitfalls also elaborating on rare differential diagnoses are highlighted with helpful hints to solve arising diagnostic difficulties. The clinical work-up and the staging examinations depending on the type of B cell infiltrate are relevant for patient care and a short overview of the main diagnostic standards is given.

Cutaneous reactive B-cell lymphoid proliferations.

Cutaneous lymphoid hyperplasia (CLH), also known as cutaneous pseudolymphoma, is a spectrum of benign conditions characterized by reactive B- and T-cell cutaneous lymphocytic infiltrates. B-cell lymphoid proliferations are a heterogenous group of non-neoplastic cutaneous diseases that must be histopathologically distinguished from cutaneous B-cell lymphomas. These proliferations can be observed as reactive phenomena to infections, medications, allergens, neoplasms, and more. Furthermore, there are many inflammatory conditions that present with reactive B-cell infiltrates, including actinic prurigo, Zoon balanitis, Rosai-Dorfman disease, and cutaneous plasmacytosis. This review summarizes multiple cutaneous B-cell lymphoid proliferations within the major categories of reactive and disease-associated CLH. Further we discuss major discriminating features of atypical CLH and malignancy. Understanding the specific patterns of B-cell CLH is essential for the proper diagnosis and treatment of patients presenting with such lesions.

Clonal cutaneous and neurosyphilis: A pitfall in pseudolymphoma diagnosis.

Syphilis is a sexually transmitted infectious disease caused by the bacterium Treponema pallidum and can cause a wide variety of cutaneous manifestations, most commonly, a papulosquamous eruption of the trunk and extremities. Treatment with penicillin is curative. We report a case of a 69-year-old man who presented with recent onset of blurry vision and a nonpainful, nonpruritic eruption of pink-to-violaceous dermal nodules on his upper trunk and upper extremities. Biopsies of two separate locations revealed a dense superficial and deep perivascular atypical lymphocytic infiltrate with admixed plasma cells, histiocytes, and eosinophils. Some scattered cells expressed CD30, PD1, BCL-6, and ICOS. T-cell receptor (TCR)-rearrangement showed an identical TCR-gamma clone between both biopsy specimens. The patient was subsequently seen by ophthalmology and diagnosed with acute anterior uveitis. Rapid plasma reagin was reactive and cerebrospinal fluid studies showed findings consistent with a diagnosis of neurosyphilis. A T. pallidum immunostain of the skin biopsies was performed upon re-review, and was diffusely positive for spirochetes at the dermal-epidermal junction and within injured vessels. The patient was treated with penicillin G with near-resolution of his skin lesions. This case highlights the unusual ability of syphilis to mimic a T-cell lymphoma with matching clones across two different biopsy sites.

Ultrasonography of cutaneous nodular pseudolymphoma at 18 and 71 MHz.

Cutaneous pseudolymphomas are reactive lymphoproliferations. The most frequent type is nodular pseudolymphoma, and to date, their ultrasonographic appearance has not been reported. We reviewed the ultrasound images of histologically confirmed nodular types of pseudolymphomas studied with 18 and 71 MHz linear probes. All lesions were predominantly hypoechoic and presented prominent vascularity. Seventy percent of cases involved dermis and hypodermis, and 30% were only dermal. Seventy percent of cases showed internal hypoechoic globules, and 100% presented a teardrop sign, more clearly detected at 71 MHz. Ultrasound can support the diagnosis, assessment of the extent, and degree of vascularity of cutaneous nodular pseudolymphomas.

Cutaneous B-Cell Pseudolymphoma (Lymphocytoma Cutis) of the Earlobe: A Poorly Recognized Complication of Ear Piercing in Children.

Background: Cutaneous pseudolymphoma (CPL) refers to a group of benign, reactive processes that mimic cutaneous lymphoma and are associated with a variety of triggering immune stimuli, including arthropod bites, drugs, and foreign bodies. In children, most cases of CPL are due to a variant of Borreliosis that is specific to Eurasia. Cutaneous pseudolymphoma secondary to ear piercing has only been documented in adults. Case Reports: We present the clinical and pathological findings of cutaneous Bcell psuedolymphoma in two adolescent patients (11-year-old female and 15-year-old male) secondary to ear piercing. Conclusion: Our report expands the clinico-pathological spectrum of CPL associated with ear piercing by documenting its occurrence in children.

Inflammatory lobular hemangioma: A vascular proliferation with a prominent lymphoid component. Review of a series of 19 cases.

In the last 30 years, there has been a strong interest in vascular proliferations. Pyogenic granuloma was not only renamed lobular capillary hemangioma, but also the conceptual interpretation was also changed from an overgrowth of granulation tissue to a genuine hemangioma (or benign vascular neoplasm). We describe 19 cases of patients who presented clinically with a vascular lesion, characteristically a pyogenic granuloma or lobular hemangioma, where the histopathological findings led to the pathologic concern for a lymphoma of the skin. These benign lesions with a dense lymphoid infiltrate were further defined on the basis of different vascular and lymphoid immunohistochemical markers as inflammatory lobular hemangiomas. We propose that given the considerable histopathological overlap between acral pseudolymphomatous angiokeratoma, T-cell rich angiomatoid polypoid pseudolymphoma of the skin, and other designations of some of these vascular proliferations with a rich and dense lymphoid infiltrate, they might constitute a spectrum of vascular lesions with varying clinical presentations.

Lichen aureus with pseudolymphomatous infiltrate.

Lichen aureus is a variant of pigmented purpuric dermatoses. The usual histopathology of lichen aureus is characterized by a subepidermal dense, band-like lymphocytic infiltrate, extravasated erythrocytes, and hemosiderin deposits. We report three patients with lichen aureus on the extremities with similar clinical, dermoscopic, and histopathological findings characterized by a dense band-like relatively deep dermal infiltrate accompanied by extravasation of erythrocytes and hemosiderin deposits occasioning a resemblance to a lymphoproliferative disorder.

EBER in situ hybridization in subcutaneous aluminum granulomas/lymphoid hyperplasia: A diagnostic clue to differentiate injection-associated lymphoid hyperplasia from other forms of pseudolymphomas and cutaneous lymphomas.

BACKGROUND: Subcutaneous vaccination or desensitization may induce persistent nodules at the injection sites. Without the knowledge of prior injection, histopathological work-up may be challenging. OBJECTIVE: Aim of this study was to contribute to the histopathological work-up of unclear subcutaneous nodules, especially their differentiation from cutaneous lymphoma. METHODS: We retrospectively reviewed clinical data and histopathological slides of four patients with subcutaneous nodules, which were suspected to suffer from cutaneous T- or B-cell lymphoma. Sections of these cases and 12 negative controls were stained with hematoxylin and eosin and a standardized immunohistochemical panel of B- and T-cell markers including EBER in situ hybridization as well as electron microscopy. RESULTS: In all cases, large histiocytes with granular cytoplasm compatible with intracellular aluminum hydroxide were present. EBER in situ hybridization revealed positive staining of these granular histiocytes while staining was absent in negative controls. LIMITATIONS: Post hoc completion of medical history revealed that vaccination or specific immunotherapy had been applied before at the biopsy site in only three out of four patients; one patient was lost to follow-up. CONCLUSION: EBER in situ hybridization is an adjunctive tool to differentiate aluminum-induced granuloma/lymphoid hyperplasia from other forms of pseudolymphoma and cutaneous B- or T-cell lymphomas.

Pulmonary nodular lymphoid hyperplasia and Sjögren's syndrome: a case report and literature review.

Pulmonary nodular lymphoid hyperplasia, also known as pseudolymphoma, is an uncommon reactive lymphoproliferative disorder of unknown etiology that can be found in Sjögren's syndrome patients. Here, we present a case of a previously healthy woman in which the incidental finding of a lung mass compatible with nodular lymphoid hyperplasia led to the subsequent diagnosis of Sjögren's syndrome. We also performed a literature review for the association between both entities and described the main clinical aspects of the reported cases. Although its rarity, we consider that pulmonary nodular lymphoid hyperplasia should be considered in the differential diagnosis of lung nodules or masses among Sjögren's syndrome patients.

Ipilimumab/nivolumab-induced pseudolymphoma in a patient with malignant melanoma.

Combination therapy with ipilimumab and nivolumab is an adjuvant treatment approach for metastatic melanoma that boasts increased 3-year survival when compared with a single immunotherapy agent. Combination therapy, however, is associated with increased toxicities, especially cutaneous side-effects. Here we present a patient with metastatic melanoma and a sudden eruption of painful nodules on the face and arms 10 days after the administration of the fourth dose of combination ipilimumab/nivolumab. Biopsies demonstrated lymphoid hyperplasia, not clinically or pathologically consistent with an infectious, malignant or autoimmune etiology; a diagnosis of pseudolymphoma secondary to ipilimumab/nivolumab was made. After a steroid taper, the lesions resolved, and the patient was restarted on nivolumab monotherapy 2 weeks later without recurrence of symptoms or disease.

Cutaneous pseudolymphoma-A review on the spectrum and a proposal for a new classification.

Cutaneous pseudolymphomas (PSLs) belong to a group of lymphocytic infiltrates that histopathologically and/or clinically simulate lymphomas. Different causative agents (e.g., Borrelia sp., injected substances, tattoo, arthropod bite) have been described, but in many cases no cause can be identified, hence the term idiopathic PSL. Clinicopathological correlation is important to make the diagnosis. Four main groups of cutaneous PSL can be distinguished based on histopathologic and/or clinical presentation: (a) nodular PSL; (b) pseudo-mycosis fungoides (pseudo-MF) and simulators of other CTCLs; (c) other PSL (representing distinct clinical entities); and (d) intravascular PSL. This article gives an overview of the histopathologic and clinical characteristics of cutaneous PSLs and proposes a new classification.

A case of cutaneous pseudolymphoma with a distinctive appearance treated successfully by intralesional interferon alpha-1b and corticosteroids.

Cutaneous pseudolymphoma (CPL) encompasses various forms of benign lymphocytic proliferative dermatoses that mimic the clinical and/or pathological changes of lymphoma. The clinical manifestations of CPL vary due to differences in the pathogenesis, and accordingly, no specific treatment has been identified. Here, we report a case of CPL on the nose, which had a distinctive appearance and was treated successfully using a combination of intralesional interferon alpha-1b and compound betamethasone (betamethasone sodium phosphate and betamethasone dipropionate). This combination may be a good option for localized CPLs at particular anatomical sites.

An instructive case of amlodipine-induced reversible granulomatous CD30+ T-cell pseudolymphoma.

We report an unusual case of drug-associated granulomatous CD30+ T-cell pseudolymphoma secondary to amlodipine. A 55-year-old Chinese man presented with a 6-month eruption of disseminated erythematous dermal papulonodules and annular infiltrated plaques over his neck and limbs symmetrically. Histopathology revealed a perivascular and interstitial infiltrate of histiocytes, eosinophils and morphologically normal lymphocytes associated with CD30 expression. The eruption improved rapidly after discontinuation of amlodipine and did not recur.

[Pathology of the nipple-areola complex : Part II. Tumors, tumor-like lesions, and supernumerary breast lesions]. / Pathologie der Mamillenregion : Teil II: Tumoren, tumorartige Läsionen und Überschussbildungen.

The nipple-areola complex is the origin of various morphologically distinct tumors and tumor-like lesions, which can be delineated from the special structures of the nipple, in particular the intramammary ducts, skin-appendages, and the intramammary stroma. Benign tumors are most frequent and this includes epithelial tumors such as mammary adenoma and syringomatous tumor of the nipple. Less commonly observed are benign mesenchymal tumors such as leiomyoma of the nipple, or tumor-like lesions like pseudo-lymphoma. With excess formations of the nipple, the different forms of polythelia and polymastia have to be considered.