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Epithelioid hemangioma (EH) is a benign vascular lesion, typically consisting of small vascular channels lined by epithelioid endothelial cells and associated with a dense lymphocytic infiltrate with eosinophils. Here, we report a rare case of EH involving large arteries. The patient presented with a nine-month history of an asymptomatic nodule on the forehead, which was thought to be an epidermal inclusion cyst. Skin biopsy revealed large arteries with clusters of epithelioid cells in the vascular walls and lumen. Scattered eosinophils were noted in the walls. Adjacent areas showed groups of small-caliber vessels lined by prominent endothelial cells and associated with a dense lymphoid infiltrate with eosinophils. No significant cytologic atypia was noted. Given the presence of the classic small vessel involvement, along with CD31 reactivity for the epithelioid cells in the large vessels, the findings are classified as EH involving large arteries, which is an uncommon subtype. There have only been a handful of such cases reported in the literature. This article is protected by copyright. All rights reserved.

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 non-painful, non-pruritic 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. 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. RPR was reactive and CSF studies showed findings consistent with a diagnosis of neurosyphilis. A Treponema 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. This article is protected by copyright. All rights reserved.

Dermatomyositis (DM) is an immune-mediated inflammatory disease characterized by pathognomic lesions in skin and skeletal muscle including lymphocytic infiltrates. It rarely presents with ectopic lymphoid structures, as other autoimmune and chronic inflammatory diseases. We describe a case of a 47-year-old male, who presented clinically with proximal muscle weakness, skin rash and elevated creatin kinase (CK) levels. The muscle biopsy revealed inflammatory myopathy, with perifascicular pathology, and scattered ectopic lymphoid follicles-like structures harboring reactive B-cells. Clonality analysis of B-cells using polymerase chain reaction ruled out malignant lymphoma. The patient responded favorably to steroid therapy, and his muscle weakness improved. In conclusion, the clinical and histopathologic features of DM can be atypical, and the presence of lymphoid follicles, although rare, is not inevitably linked to an unfavorable prognosis.

Introduction.Uveal melanoma is a malignant neoplasm of the vascular tract of the eye. Prevention of metastasis of this tumor is one of the main tasks in order to increase the rates of relapse-free survival of patients. Despite the pronounced immunosuppressive activity of uveal melanoma cells, its lymphocytic microenvironment exerts its antitumor effect.Aim of the study.Compare the lymphocytic microenvironment of primary uveal melanomas and distant metastases (to the liver).Мaterials and methods.The tissue material of choroid melanoma after enucleation and the material of tumor metastases for the period 2013-2018 were studied. An immunohistochemical study was performed using CD8, CD4, and CD56 markers for the qualitative and quantitative assessment of lymphocytes in the tumor stroma.Results.Differences were found in the lymphocytic infiltration of the uveal melanoma stroma and its distant metastases. A statistically significantly greater representation of CD4, CD8-lymphocytes and CD56 cells in tumor metastases than in primary melanoma tissue samples, with CD4-lymphocytes predominant. A direct high-strength correlation was registered between the number of CD4-lymphocytes and CD8-lymphocytes.Discussion.Malignant cells actively modify their cellular and stromal-vascular environment, ensuring their active growth and reproduction. The question of the immune reactivity of the surrounding cells in relation to uveal melanoma remains debatable. According to our data, which is consistent with a number of other studies, uveal melanoma cells do not completely evade the body's immune response. Thus, the determination of possible points of antitumor exposure can be based on a detailed study of the microenvironment of uveal melanoma.Conclusions.The pronounced lymphocytic infiltrate found in uveal melanoma metastases in comparison with the primary tumor indicates an active immune response of the body to the tumor. These results of our study confirm the importance of further studying the immune-mediated antitumor effect on uveal melanoma and the need to investigate possible approaches to immunotherapy.

Mycosis fungoides (MF) is a subtype of primary cutaneous T-cell lymphoma (CTCL) with an indolent course that rarely progresses. Histologically, the lesions display a superficial lymphocytic infiltrate with epidermotropism of neoplastic T-cells. Hypopigmented MF is a rare variant that presents with hypopigmented lesions and is more likely to affect young patients. The etiology of the hypopigmentation is unclear. The aim of this study was to assess melanocyte loss in MF through immunohistochemistry (IHC) with SOX10. Twenty cases were evaluated, including seven of the hypopigmented subtype. The neoplastic epidermotropic infiltrate consisted predominantly of CD4+ T-cells in 65% of cases, CD8+ T-cells were present in moderate to abundant numbers in most cases. SOX10 IHC showed a decrease or focal complete loss of melanocytes in 50% of the cases. The predominant neoplastic cell type (CD4+/CD8+), age, race, gender, histologic features, and reported clinical pigmentation of the lesions were not predictive of melanocyte loss. A significant loss of melanocytes was observed in 43% of hypopigmented cases and 54% of conventional cases. Additional studies will increase our understanding of the relationship between observed pigmentation and the loss of melanocytes in MF.

Background Hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) is a chronic Epstein-Barr virus (EBV)-positive lymphoproliferative disease which may either present as an indolent condition or progress to a systemic T-cell lymphoma. Methods All HVLPD diagnosed over a 10-year period were retrieved and clinical data regarding sex, age, oral and systemic manifestations, and clinical follow-up were obtained. Immunohistochemistry was done in order to characterize the lymphoid cells and in situ hybridization was used to demonstrate the presence of EBV. Results Eleven cases were included, with a male predominance and a mean age of 25.1 years. Buccal mucosa and the lips were the most affected oral sites, appearing as painful ulcers. All patients exhibited facial oedema, usually affecting the lips, nose, and periorbital region. The clinical course was gradual but progressive, with four patients having fever and 3 showing lymphadenopathies. All cases showed a moderate to severe lymphocytic infiltrate with angiotropism, angiocentricity and epidermotropism. Two cases affecting the lip skin exhibited a periappendageal lymphocytic infiltrate. Few large pleomorphic cells were found, surrounded by smaller and medium-sized lymphoid cells, as well as reactive plasma cells, macrophages, neutrophils, and eosinophils. All lesions exhibited a cytotoxic T cell (CD8 +) phenotype with a variable proliferative index. All cases were associated with EBV and all patients died due to complications of the disease. Conclusions HVLPD is a rare disease that may show oral involvement with a cytotoxic T-cell phenotype, and is strongly associated with EBV. As shown in this series, HVLPD may show aggressive clinical behaviour.

Carcinoma cuniculatum (CC) is a rare variant of squamous cell carcinoma (SCC) that is characterized by minimal cytologic atypia and a unique deeply infiltrative growth pattern resembling rabbit burrows (cuniculi). With less than 75 cases reported in the head and neck, the clinical and pathologic spectrum of this entity remains poorly understood. A retrospective review of the clinical and pathologic features of archival cases of oral CC was performed. A total of six cases of oral CC were identified. Age ranged from 25-77 years; the male-to-female ratio was 5:1. All patients had a long-standing history of tobacco and betel-quid consumption. The tumors were distributed in the gingivobuccal sulcus (n = 2), the tongue (n = 2), buccal mucosa (n = 1), and the palate (n = 1). Histology in all cases typically revealed a tumor composed of well-differentiated squamous epithelium, devoid of atypia, lining deeply infiltrative, large-sized, branching, keratin-filled cavities, resembling rabbit-burrows. Dense lymphocytic infiltrates and discharging micro-abscesses were regular features. Underlying bone invasion and lymph node metastasis were observed in 1 patient. One patient with a tongue tumor developed locoregional recurrence at 10 months while none developed distant metastasis. Oral CC is a rare and under-recognized variant of SCC with locally aggressive behavior. Lack of familiarity with this variant exacerbated by the absence of cytologic anaplasia makes CC susceptible to multiple negative biopsies and erroneous diagnoses. Awareness of this clinicopathologic entity is essential to allow its accurate diagnosis and optimal management.

Introduction: Papillary thyroid microcarcinoma (PTMC) is defined as a PTC measuring 1 cm or less, incidentally discovered. The aim of this study was to determine whether small (Materials and methods: All consecutive PTMC cases registered at the Department of Pathology, Târgu-Mureş Emergency County Hospital between 2003-2014 were reviewed. The following have been assessed: tumor size, subcapsular versus nonsubcapsular location, extrathyroidal extension/invasion into the perithyroidal adipose tissue, multifocality, resection margins, lymph node involvement, histological variant, tumor border, stromal reaction (fibrosis/desmoplasia/sclerosis), presence of plump pink cells, nuclear features of the tumor cells, intratumoral lymphocytic infiltrate, multinucleated giant cells, psammoma bodies and stromal calcification. The cases were split in two categories: small (< 5mm) and large (≥ 5mm) PTMCs and the pathological features were evaluated in comparison. Results: Our study included 206 cases, 91 large and 115 small PTMCs, respectively. Large PTMCs were significantly associated with the presence of plump pink cells (p=0.002), well developed PTC nuclear features (p=0.003), stromal reaction (fibrosis/desmoplasia/sclerosis) (pConclusions: Our results have shown that small (

Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder is a benign lymphoproliferative disorder composed of small-sized to medium-sized pleomorphic cells expressing a follicular helper T-cell phenotype. Jessner lymphocytic infiltrate and tumid lupus are cutaneous conditions characterized by the presence of rich dermal lymphocytic infiltrates with a superficial, deep, perivascular and periadnexal distribution that include copious amounts of dermal mucin deposition. We report 2 cases of primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder presenting with markedly increased dermal mucin, mimicking both Jessner lymphocytic infiltrate and tumid lupus and provide a review of the differential diagnosis and highlight key distinguishing features.

Although the erythema migrans (EM) skin rash is traditionally considered a hallmark of Lyme disease, other dermatological manifestations of the tickborne disease are less well known. We describe a 49-year-old woman with erosive genital ulcerations, secondary EM rashes and jagged skin lesions associated with Lyme disease. The skin rashes exhibited fibers characteristic of Morgellons disease. Molecular testing confirmed the presence of Borrelia DNA in both vaginal culture and serum specimens. In further studies on a secondary EM lesion containing filaments, Gömöri trichrome staining revealed the presence of collagen in the filaments, while Dieterle and anti-Borrelia immunostaining revealed intracellular and extracellular Borrelia organisms. Intracellular staining for Borrelia was also observed in lymphocytic infiltrates. Lyme disease may present with a variety of genital lesions and dermatological manifestations including Morgellons disease. Careful evaluation is required to determine the presence of Borrelia organisms associated with these dermopathies.

We report the clinical and histopathological features of hydroa vacciniforme-like lymphoproliferative disorder in five indigenous and Mestizo children. All the children resided at higher altitudes, experiencing maximal solar exposure. All cases presented with prurigo along with Epstein-Barr virus infection. Histopathologic examination showed an atypical, CD30 + lymphocytic infiltrate with angiocentricity in all, while three cases demonstrated panniculitis-like infiltrate.

Amiodarone (AMD) is a class III antiarrhythmic drug whose chronic or high dosage administration alters the tests of thyroid function. AMD is also associated with hypothyroidism or thyrotoxicosis. Total thyroidectomy is an efficient treatment of AMD-induced thyrotoxicosis in cases resistant to medical therapy, worsening of cardiac function and/or severe thyrotoxicosis. Although AMD is a widely used drug, its pathological consequences are not well known. We describe the pathological findings in the thyroid gland of a patient who underwent total thyroidectomy due to AMD-induced thyrotoxicosis. The surgical specimen was macroscopically normal, but histologically showed multiple follicles totally or partially invaded by clear vacuolated (foamy) histiocytes, sometimes multinucleated. Loss of thyrocytes, breaks in the follicular basal membrane and stromal fibrosis could also be appreciated but no lymphocytic infiltrates were found. An awareness of these histopathological features is particularly important for surgical pathologists, especially as there are very few published reports describing these alterations.

It is not yet entirely clear what is the relevance of skin symptoms and what clinical implications are related to their appearance in COVID‐19 patients. We describe two cases of COVID‐19‐associated pneumonia, which presented skin manifestations in advanced stage of illness, when nasopharyngeal swabs became negative for SARS‐CoV‐2. The first case presented erythematous, maculopapular lesions; the second developed petechial, vesicular and blood‐encrusted lesions on the limbs. Histopathology documented perivascular lymphocytic infiltrates, with prevalent CD4+ T‐cells in both patients. The research of SARS‐CoV‐2 in tissues with real time RT‐PCR was negative. Basal keratinocytes displayed C4d deposits in one case, who developed laboratory signs indicative of a procoagulative condition at the same time as the skin rash. Skin manifestations during SARS‐CoV‐2 infection seem to be clinically relevant and further studies are necessary to assess if they are linked to systemic complications, lack of viral clearance or cascades of immune responses induced by the virus, even in patients affected by mild pneumonia.

Background Alopecia areata (AA) is a common cause of hair loss. It is mediated by T lymphocytes. Scalp biopsy findings in AA differ according to the disease phase and activity. Objectives To study the cellular infiltrate in the transverse section of scalp biopsy of AA at different disease stages and in relation to disease activity. Methods The study was performed on 40 subjects with AA. A 4-mm punch biopsy was obtained from an AA scalp lesion. Biopsies were sectioned horizontally; 2 anatomical levels were studied (mid dermal and deep dermal levels). Results Ninety-five percent of AA showed noncicatrical alopecia. A significant relation was found between the course of AA and the terminal:vellus ratio. Peribulbar lymphocytic infiltration was seen in 70% of cases. Mast cells were observed in 87.5% of cases, including fibrous tract and around the arrector pili muscles. Eosinophils were detected in the scalp biopsy of 22.5% of cases. Course and activity of AA were significantly related to the peribulbar lymphocytic cell infiltration but not to mast cells and eosinophils. Conclusion Although a peribulbar lymphocytic infiltrate is the classical finding of AA, it is absent in the chronic phase. Mast cells are commonly found in the scalp biopsy of AA and could explain the potential therapeutic effect of antihistamines.

We documented fetal death associated with intrauterine transmission of severe acute respiratory syndrome coronavirus 2. We found chronic histiocytic intervillositis, maternal and fetal vascular malperfusion, microglial hyperplasia, and lymphocytic infiltrate in muscle in the placenta and fetal tissue. Placenta and umbilical cord blood tested positive for the virus by PCR, confirming transplacental transmission.

Cutaneous pseudolymphomas are a heterogeneous group of reactive lymphocytic infiltrates, which simulates cutaneous lymphomas clinically and histologically. Although in many cases the pathogenesis is not understood, a broad spectrum of different agents inducing pseudolymphomas has been reported. Cutaneous pseudolympomas are distinguished in four main groups: (a) nodular pseudolymphomas, (b) pseudo-mycosis fungoides (pseudo-MF) and simulators of other CTCLs, (c) other pseudolymphomas and (d) an intravascular pseudolymphoma. This article focuses on pseudolymphoma entities related to infections or inflammatory skin diseases. The integration of the clinical presentation and patients’ history is mandatory for the correct diagnosis.

Introduction: The relentless increase in the worldwide incidence of obesity has intensified the need for new treatments that are effective and safe. The intragastric balloon (IGB) is one such treatment that emerged. Fungal biofilms formed on medical devices and their relationship to infectious diseases is now well-established. However, studies regarding the microbial contamination suffered by this device are still incipient. Case Report: We report here the first case of an IGB affected by a Candida glabrata biofilm, characterized by microbiological and scanning electron microscopy techniques. We verified yeasts, of the same species, in the mucosa of the duodenum, which was accompanied by lymphocytic infiltrate, as revealed through histopathological investigation. Conclusion: Our findings highlight the importance of biofilm investigation on this type of device and to recognize the potential repercussions for the carrier since obese patients are immunocompromised and may undergo surgical interventions, thereby aggravating the risk of candidemia.

Acute cellular rejection after cardiac transplantation surgery is routinely monitored by pathological assessment of haematoxylin and eosin (H&E) histology of endomyocardial biopsies (EMB). Unfortunately, there is considerable variation in the diagnosis of rejection that has been attributed to the subjectivity involved in assessing the degree of (a) inflammatory infiltrate and (b) myocyte damage. In this work, we sought to investigate the potential of high contrast confocal microscopy for numerically assessing inflammatory infiltrate and myocyte damage in EMB histology. Confocal microscopy was used to capture images from EMB fluorescently labelled for nuclei (DAPI), f-actin (phalloidin), troponin-T (anti-body), and extracellular matrix and cell border (wheat germ agglutinin). Images from 28 biopsy procedures were captured. Standard pathological grading of H&E histology identified the following rejection gradings: 6 0R, 16 1R, 6 2R and no 3R. Confocal imaging was able to identify equivalent features of rejection provided by H&E histology but at higher contrast facilitating quantification. Lymphocytic infiltrate was calculated as the ratio of non-myocyte nuclei to total nuclei. This metric was found to be significantly higher in the biopsies from 2R patients compared to both 1R and 0R patients (P < .05). Myocyte damage was quantified as the loss of troponin-T labelling normalised to f-actin labelling. This metric of myocyte damage found significantly lower amounts of troponin-T in the biopsies from 2R patients compared to those with a 0R rejection grading (P < .05). Confocal imaging and simple image processing routines show potential for numerically assessing both inflammatory infiltrate and myocyte damage in endomyocardial biopsy.

Introduction Studies have shown that the PD-1/PD-L1 immunomodulatory pathway slows down anti-tumor immunity in a number of cancers. The description of the expression of these molecules has never been performed in anal low-grade/high grade squamous intra-epithelial lesions (LSIL/HSIL respectively). Materials and methods Patients followed in the AIN3 cohort were routinely sampled. For each selected sample, an immunohistochemical study was performed with anti-CD8, PD-1, PD-L1 antibodies. The presence and distribution of CD8+ lymphocytes, and the presence of PD-1+ lymphocytes and PD-L1+ epithelial cells were assessed. The comparison of these characteristics was performed between the HSIL and LSIL groups. Results 33 patients were included and 78 samples selected (60 HSIL and 18 LSIL). CD8+ lymphocytes were observed more frequently in HSIL versus LSIL in the lamina propria or intra epithelial (respectively 90% vs. 60%, p = 0.01; and 62% vs. 33%, p = 0.04). PD-1+ lymphocytes were observed more frequently in HSIL versus LSIL (41% vs 11%, p = 0.03). There was no difference between HSIL and LSIL for PD-L1+ epithelial cells. Conclusions Anal dysplastic lesions are accompanied by an inflammatory lymphocytic infiltrate expressing CD8 and PD-1, more frequent in high-grade lesions. These results highlight the involvement of the PD-1/PD-L1 pathway in the natural history of anal dysplasia.

Melanomas with complete histological regression have been seen very infrequently. On the other hand, the diagnosis of metastatic melanoma is based on the histopathology and positivity of markers such as S100, Melan-A, and HMB-45 whose sensitivity is 99%, 82%, and 76%, respectively. It is very rare that metastatic melanomas and even more primary melanoma are negative for all of these markers. In these rare cases, there is usually a known primary. We present the case of a 82-year-old woman with a erythematous mass in the left groin and a 1-cm black-bluish irregular nodule on the skin of the ipsilateral foot. This lesion was clinical and dermoscopically compatible with primary melanoma. In the histological evaluation of the skin, a dermis full of melanophages and hemosiderophages were found in a background of fibrosis, scarce lymphocytic infiltrate, and neovascularization. Any cells expressing melanocytic markers were observed. It was diagnosed as tumoral melanosis. Lymph nodes showed a proliferation of atypical epithelioid cells with eosinophilic cytoplasm. Mitosis was conspicuous. Tumoral cells were vimentin and CD99 positive, and S100, CD34, HMB-45, Melan-A, SOX 10, tyrosinase, C-KIT, CD45, and CKAE1/AE3 negative, and BRAF-V600 mutated was detected. During follow-up, atypical vitiligo-like lesions were discovered, suggesting the diagnosis of metastatic melanoma totally regressed in our patient.

Lichenoid granulomatous dermatitis (LGD) is a histopathologic pattern with a band-like lymphocytic infiltrate, typical of lichenoid dermatitis, combined with dermal histiocytes and granulomatous inflammation. Prior reports have described cases of LGD caused by non-tuberculous mycobacteria, with evidence of intralesional acid-fast bacilli or mycobacterial DNA. Herein, we report a patient with pulmonary and extrapulmonary Mycobacterium tuberculosis infection who developed LGD. No evidence of M. tuberculosis was detected within the cutaneous lesions, suggesting a potential delayed-type hypersensitivity reaction to tuberculosis.

Composite lymphoma is defined as two or more morphologically and immunophenotypically distinct lymphoma clones that occur in the same tissue site. The occurrence of cutaneous composite lymphoma (CCL) is extremely rare. Here we report a unique case of CCL consisting of Hodgkin lymphoma (HL) and mycosis fungoides (MF). Our patient presented with longstanding erythematous plaques on the skin and later developed axillary lymph node enlargement. Histopathologically, the skin lesions were characterized by a dense dermal lymphocytic infiltrate with prominent epidermotropism of pleomorphic T-cells, consistent with typical MF. Nonetheless, scattered large atypical cells resembling Reed-Sternberg (R-S) cells were interspersed among these atypical T-cells in the deep dermis. Immunophenotyping suggested a HL origin of these R-S cells. Monoclonality of T-cell receptor beta gene was detected in the skin, monoclonal immunoglobulin heavy chain gene rearrangement was identified in these R-S cells microdissected from the deep dermis, confirming the origin from HL. The lymph node biopsy showed nodular sclerosis classic Hodgkin lymphoma. Therefore, CCL of HL and MF, with lymph node HL was diagnosed. The lesions of this patient responded to a sequential treatment to HL and MF. Being aware of this rare CCL facilitates correct diagnosis and proper clinical management.

Purpose In 2012, four patients with multiple asymptomatic, indolent, unilateral, choroidal lesions were described. We suspected benign-behaving lymphocytes infiltrating the choroid. This article expands the number of patients and duration of follow-up and speculates further on the etiology. Although histopathologic confirmation of these lesions is still unknown, the natural course of these patients is excellent and should be distinguished from aggressive choroidal lymphoma. Methods To qualify for the study, the patients had to meet the following criteria: 1) Patients collected had asymptomatic choroidal infiltrates as demonstrated in the figures; 2) absence of vitreous cells; 3) no evidence of concomitant systemic malignancy; 4) no systemic inflammatory diseases, including sarcoidosis; 5) no birdshot chorioretinopathy; 6) no conjunctival or orbital lesions; and 7) advanced multimodal imaging and clinical follow-up were performed. Results There were 11 eyes of 11 patients seen. Follow-up ranged from 4 months to 12 years and 1 month (mean 50.2 months; median 24 months). Systemic workup was unrevealing. No patients in this cohort developed systemic, conjunctival, orbital, or vitreoretinal lymphoma or inflammatory disease. No patients developed symptoms or vision loss. Conclusion This entity is an indolent choroidal infiltrative disease. It resembles some cases of choroidal lymphoma and may represent an indolent lymphocytic infiltrate.

Hyperkeratosis lenticularis perstans (HLP), or Flegel's disease (FD), is a rare disorder of keratinization first described in 1958 by Flegel. HLP is characterized by asymptomatic small papules distributed symmetrically on the dorsal feet and lower part of the legs. It typically presents in the fourth or fifth decade of life. FD has been reported more commonly in women, and little is known about the pathogenesis of this rare dermatosis. Histological examination is mandatory to confirm the diagnosis, and the characteristic features are: focal compact hyperkeratosis, thinned stratum malpighii, epidermal atrophy, and a dense, band-like lymphocytic infiltrate in the papillary dermis. The treatment of FD is challenging, and a fully effective standard therapy does not exist. We report four cases of HLP that have been diagnosed at the Dermatology Unit of IRCCS Ca' Granda Ospedale Maggiore Policlinico in Milan, Italy, and a literature review is enclosed.

Lichen Planus is subacute or chronic inflammatory immune mediated disease that may involve skin, mucous membranes, hair follicles and nails. Lichen Planus is characterized by epidermal thickening, liquefaction, degeneration of basal cell layer, appearance of civatte bodies and dense lymphocytic infiltrate in a band like pattern along dermoepidermal junction. Bcl-2 plays important role in cellular protection against apoptosis. COX-2 plays important role in inflammation, tumor growth, invasion and inhibition of apoptosis. In this study 50 cases of clinically and histopathologically proven Lichen Planus were studied for expression of Bcl-2 and COX-2 by immunohistochemical staining. The results were compiled and analysed statistically.

Purpose Immune checkpoint inhibitors have recently been approved by the US FDA as first and/or second line therapy in a subset of cancer types. Recent evidence suggests that the quantity of tumor infiltrating lymphocytes (TILs) influences the likelihood of response to immune checkpoint inhibitors. Here, we set out to assess the density of CD8+ lymphocytes in a wide range of different cancer types and subtypes. Methods The density of CD8+ lymphocytes was compared across different cancer types using tissue microarrays (TMAs) composed of up to 50 tumor samples each from 84 different cancer types and subtypes. In total 2652 cancers and 608 normal tissues were successfully analyzed by CD8 immunohistochemistry followed by automated image analysis of digitized slides. Results We found that the median CD8+ lymphocyte counts ranged from 6 cells/mm2 in pleomorphic adenoma up to 1573 cells/mm2 in Hodgkin’s lymphoma. The CD8 counts were generally lower in normal tissues compared to cancer tissues. Blood vessels of the spleen were the only non-lymphatic tissue staining positive for CD8. Tumor types approved for checkpoint inhibitor therapy, including malignant melanoma (81), muscle invasive urothelial carcinoma (119), small cell lung cancer (120), clear cell renal cell cancer (153), squamous cell carcinoma (189) and adenocarcinoma of the lung (328) as well as Hodgkin’s lymphoma (1573) were all ranking among the upper half of our list. Comparably high CD8 densities (median cells/mm2) were also found in several rare and aggressive cancer types including Merkel cell carcinoma (70), angiosarcoma (95), anaplastic thyroid cancer (156) and embryonal carcinoma of the testis (186). In 73 of the 84 analyzed cancer types, the highly variable CD8 counts occasionally exceeded the average CD8 count of tumors for which checkpoint inhibitors have been approved. Conclusion These data support the concept that among most tumor types at least some individual cancers may benefit from treatment with immune checkpoint inhibitors.

Background Macular lymphocytic arteritis most commonly presents as hyperpigmented macules on the lower limbs. The pathogenesis of this disease is still unclear and there is an ongoing debate regarding whether it represents a new form of cutaneous vasculitis or an indolent form of cutaneous polyarteritis nodosa. Objective To describe clinical, histopathological, and laboratory findings of patients with the diagnosis of macular lymphocytic arteritis. Methods A retrospective search was conducted by reviewing cases followed at the Vasculitis Clinic of the Dermatology Department, School of Medicine, University of Sao Paulo, between 2005 and 2017. Seven patients were included. Results All cases were female, aged 9–46 years, and had hyperpigmented macules mainly on the legs. Three patients reported symptoms. Skin biopsies evidencing a predominantly lymphocytic infiltrate affecting arterioles at the dermal subcutaneous junction were found, as well as a typical luminal fibrin ring. None of the patients developed necrotic ulcers, neurological damage, or systemic manifestations. The follow-up ranged from 18 to 151 months, with a mean duration of 79 months. Study limitations This study is subject to a number of limitations: small sample of patients, besides having a retrospective and uncontrolled study design. Conclusions To the best of the authors’ knowledge, this series presents the longest duration of follow-up reported to date. During this period, none of the patients showed resolution of the lesions despite treatment, nor did any progress to systemic vasculitis. Similarities between clinical and skin biopsy findings support the hypothesis that macular lymphocytic arteritis is a benign, incomplete, and less aggressive form of cutaneous polyarteritis nodosa.

Introduction: Insufficient hair growth after hair transplant, as well as erythema and perifollicular scaling, may be diagnosed as lichen planopilaris and treated as such based on clinical and histopathological findings. The purpose of this study is to observe graft biopsies of patients after uncomplicated hair transplants and to discuss if histological findings are enough to diagnose lichen planopilaris. Methods and Results: Eight patients diagnosed with androgenetic alopecia who were submitted to hair transplant were enrolled. In each of the participants, a scalp biopsy was performed in the receptor area and in the adjacent area. Biopsies were performed between 6 months and 1 year after surgery. Exams were analyzed by 3 pathologists. The t test was performed for paired observations, comparing the transplanted and the nontransplanted area for lymphocytic infiltrate and fibrosis. The significance level was considered as 5% (p < 0.05). Four of 8 participants had perifollicular lymphocytic infiltrate, from moderate to dense intensity in the recipient area. Fibrosis was seen in 6 patients. These findings were not seen in the control area. Conclusions: It is questioned whether lymphocytic infiltrate and fibrosis may be expected in patients who are submitted to normal hair transplants.

Neuronal/mixed glioneuronal tumors are central nervous system neoplasms composed of neoplastic neuronal cell components or a mixture of glial and neuronal elements. They occur in cerebral hemispheres, posterior fossa, and spinal cord. Compared with other tumors at these locations, diencephalic neuronal/glioneuronal tumors are very rare and therefore not well characterized. We hereby performed clinicopathologic evaluation on 10 neuronal/glioneuronal tumors arising from the diencephalic region. Morphologically, these tumors resemble their histologic counterparts in other locations, except that lymphocytic infiltrates and microcalcifications are more common than Rosenthal fibers or eosinophilic granular bodies. The BRAFV600 mutation rate is 75%. Given the high percentage of samples being small biopsy specimens, the subtle histologic features and molecular findings greatly aided in establishing the pathologic diagnosis in several cases. At a median follow-up of 42 months, 71% of the tumors demonstrated radiological recurrence or progression, with median progression-free survival of 18 months. Recurrence/progression is observed in tumors across different histologic subtypes, necessitating additional therapies in 56% of the cases. Despite their bland histology, diencephalic neuronal/glioneuronal tumors are not clinically indolent. Their frequent recurrences warrant a close follow-up, and the prevalent BRAF mutation makes MAPK pathway inhibition a plausible treatment option when conventional therapies fail.

Lung adenocarcinoma (LUAD), the most common non‐small‐cell lung cancer, is characterized by a dense lymphocytic infiltrate, which indicates that the immune system plays an active role in the development and growth of this cancer. However, no investigations to date have proposed robust models for predicting survival outcome for patients with LUAD in terms of tumour immunology. A total of 761 LUAD patients were included in this study, in which the database of The Cancer Genome Atlas (TCGA) was utilized for discovery, and the Gene Expression Omnibus (GEO) database was utilized for validation. Bioinformatics analysis and R language tools were utilized to construct an immune prognostic model and annotate biological functions. Lung adenocarcinoma showed a weakened immune phenotype compared with adjacent normal tissues. Immune‐related gene sets were profiled, an immune prognostic model based on 2 immune genes (ANLN and F2) was developed with the TCGA database to distinguish cases as having a low or high risk of unfavourable prognosis, and the model was verified with the GEO database. The model was prognostically significant in stratified cohorts, including stage I‐II, stage III‐IV and epidermal growth factor receptor (EGFR) mutant subsets, and was considered to be an independent prognostic factor for LUAD. Furthermore, the low‐ and high‐risk groups showed marked differences in tumour‐infiltrating leucocytes, tumour mutation burden, aneuploidy and PD‐L1 expression. In conclusion, an immune prognostic model was proposed for LUAD that is capable of independently identifying patients at high risk for poor survival, suggesting a relationship between local immune status and prognosis.

Background and Objectives: Ovarian cancer is the leading cause of death among gynecological tumors. PD-1/PD-L1 immunoregulatory mechanism is activated in ovarian cancers. Lymphocyte infiltration is a significant factor that affects its expression. We analyzed the correlation between localization of lymphocytic infiltrate and PD-L1 expression in epithelial ovarian tumors. Materials and Methods: PD-L1 expression was analyzed in 328 subjects, 122 with epithelial ovarian carcinoma, 42 with atypical proliferative tumor, and 164 with benign epithelial ovarian tumor. Expression in central and invasive tumor parts in epithelial ovarian carcinoma was combined with the most pronounced lymphocyte reaction. Immunohistochemical analysis was performed using the tissue microarray and correlated with a set of histopathology parameters. Results: PD-L1 expression was most prominent in epithelial ovarian carcinoma with different levels of expression observed between invasive and central tumor segments. A high level of PD-L1 expression on tumor cells was more frequently present in the invasive than in the central tumor parts (p < 0.001) only in high-grade serous ovarian carcinoma (HGSC). There was no significant correlation between peritumoral lymphocytic infiltrate and PD-L1 expression regardless of tumor segment. In the central tumor parts of HGSC, there was a correlation of intratumoral lymphocytic infiltrate with a higher level of PD-L1 expression (p = 0.003). Conclusions: The most prominent PD-L1 expression was observed in the invasive tumor parts of HGSC. Only the central parts of the HGSC exhibited significant PD-L1 expression in association with considerable intratumoral lymphocytic infiltrate.

Aims Intracranial myxoid mesenchymal tumors (IMMTs) with fusions between EWSR1/FUS and CREB transcription factors have morphologic overlap with myxoid angiomatoid fibrous histiocytoma (mAFH) and myoepithelial tumor/carcinoma (MET/MEC). We aimed to study the clinicopathologic and genetic spectrum of extracranial IMMT-like tumors and their relationships with mAFH and MET/MEC. Methods Twelve extracranial tumors harboring EWSR1/FUS-CREB fusions across different histologic groups were characterized using RNA sequencing, FISH and/or RT-PCR. Results There were 4 IMMT-like neoplasms, 3 MET/MECs, and 5 mAFHs from the tibia (n=1), oral cavity (n=2), and soft tissues (n=9; 5 in the extremities), harboring EWSR1-ATF1 in 4 cases, FUS-CREM and EWSR1-CREM in 2 each, and EWSR1-CREB1 in 2. Multinodular growth, reticular/cording/trabecular arrangements, myxocollagenous matrix, and lymphocytic infiltrates variably prevailed among the 3 groups. mAFHs were characterized by cells with syncytial cytoplasm. IMMT-like neoplasms and MET/MECs shared cells with distinct boundaries, but only MET/MECs expressed GFAP and/or S100. MUC4 and ALK were expressed in some IMMT-like neoplasms (2/4; 2/4) and mAFH (2/5; 1/5). Pan-TRK reactivity was observed in two IMMT-like neoplasms with upregulated NTRK3 mRNA and one MEC. Local recurrences, typically ≥ 12 months postoperatively, developed in 2/3 IMMT-like neoplasms, 1/2 MET/MECs, and 0/4 mAFHs with follow-up. No definite associations were found between fusion types and histology, immunoprofile or outcome. Conclusions We demonstrated the similarities and differences among 3 extracranial myxocollagenous tumor groups sharing EWSR1/FUS-CREB fusions. Oral IMMT-like neoplasms harboring FUS-CREM or EWSR1-ATF1 and FUS-CREM-positive

High-risk Myelodysplastic syndromes (MDS) represent therapeutical challenges and are usually managed with hypomethylating agents such as azacitidine. Given the lack of data in the literature concerning azacitidine effects on bone marrow, we retrospectively analyzed 57 high-risk MDS cases in order to identify any changes induced by azacitidine therapy or relevant correlations between therapy response and pre- or post-treatment features. Azacitidine treatment had no significant impact on bone marrow cellularity or morphological dysplastic features. On the contrary, although not statistically significant, we observed a slight decrease in CD34+ and CD117+ blasts and p53+ precursors after treatment. Moreover, pre-treatment IPSS-R cytogenetic score (p = 0.004), lymphocytic infiltrate (p = 0.017) and p53+ elements (p = 0.001) correlated with AML progression, pre-treatment lymphocytic infiltrate was also linked to better response to therapy (p = 0.004), suggesting an anti-tumoral role of bone marrow microenvironment. Post-treatment blast count impacted negatively on overall survival (p = 0.035) and risk of leukemic progression (p = 0.04), while both post-treatment lymphocytic infiltrate and p53+ elements showed significant correlation with treatment response (p = 0.004 and p = 0.003 respectively). Higher post-treatment p53+ elements correlated also with risk of leukemic progression (p = 0.013). Our results suggest the possible role of lymphocytic infiltrate and p53+ elements as predictive markers in MDS treated with azacitidine, disclosing new chapters in the understanding of MDS evolution and treatment.

Familial pulmonary fibrosis (FPF) is a monogenic disease most commonly involving telomere- (TERT) or surfactant- (SFTP) related mutations. These mutations have been shown to alter lymphocytic inflammatory responses, and FPF biopsies with histological lymphocytic infiltrates have been reported. Recently, a model of a surfactant mutation in mice showed that the disease initially started with an inflammatory response followed by fibrogenesis. Since inflammation and fibrogenesis are targeted by different drugs, we investigated whether the degree of these two features co-localize or occur independently in different entities of FPF, and whether they influence survival. We quantified the number of lymphocyte aggregates per surface area, the extent of diffuse lymphocyte cell infiltrate, the number of fibroblast foci per surface area, and the percentage of fibrotic lung surface area in digitally scanned hematoxylin and eosin (H&E) sections of diagnostic surgical biopsies of patients withTERT-related FPF (TERT-PF;n= 17),SFTP-related FPF (SFTP-PF;n= 7), and sporadic idiopathic pulmonary fibrosis (sIPF;n= 10). For comparison, we included biopsies of patients with cellular non-specific interstitial pneumonia (cNSIP;n= 10), an inflammatory interstitial lung disease with high lymphocyte influx and usually responsive to immunosuppressive therapy. The degree of inflammatory cell infiltrate and fibrosis in TERT-PF and SFTP-PF was not significantly different from that in sIPF. In comparison with cNSIP, the extent of lymphocyte infiltrates was significantly lower in sIPF and TERT-PF, but not in SFTP-PF. However, in contrast with cNSIP, in sIPF, TERT-PF, and SFTP-PF, diffuse lymphocyte cell infiltrates were predominantly present and lymphocyte aggregates were only present in fibrotic areas (p < 0.0001). Furthermore, fibroblast foci and percentage of fibrotic lung surface were associated with survival (p= 0.022 andp= 0.018, respectively), while this association was not observed for lymphocyte aggregates or diffuse lymphocytic infiltration. Inflammatory cells in diagnostic lung biopsies of TERT-PF, SFTP-PF, and sIPF were largely confined to fibrotic areas. However, based on inflammation and fibrosis, no differences were found between FPF and sIPF, substantiating the histological similarities between monogenic familial and sporadic disease. Furthermore, the degree of fibrosis, rather than inflammation, correlates with survival, supporting that fibrogenesis is the key feature for therapeutic targeting of FPF.

Halo nevi, known as leukoderma acquisitum centrifugum, Sutton nevus, leukopigmentary nevus, perinevoid vitiligo, or perinevoid leukoderma, together with vitiligo and melanoma-associated hypopigmentation, belong to the group of dermatoses designated as immunological leukodermas. The etiology and pathogenesis of halo nevi has not been fully elucidated. There are several mechanisms through which a lymphocytic infiltrate can induce tumoral regression. In this review, we aimed to update the knowledge about Sutton nevi starting with the clinical appearance and dermoscopic features, continuing with information regarding conventional microscopy, immunohistochemistry, and the immunological mechanisms responsible for the occurrence of halo nevi. We also included in the article original unpublished results when discussing dermoscopic, pathologic and immunohistochemical results in halo nevi. Sutton nevi are valuable models for studying antitumor reactions that the human body can generate. The slow and effective mechanism against a melanocytic skin tumor can teach us important lessons about both autoimmune diseases and anticancer defenses.

The study aims to report a rare case of Lymphoepithelioma-Like Carcinoma of The Breast which may also aid in knowledge of literature to other colleagues. Lymphoepithelioma-like carcinoma (LELC) is an undifferentiated carcinoma, it occurs in the organs that exclude nasopharynx, but has the same morphology as that of nasopharangeal lymphoepithelioma. It has been described in several organs, however it is rarely seen in the breast. Due to the undifferentiated appearance of neoplastic cells and the presence of prominent lymphocytic infiltrate, LELC can wrongly be diagnosed as lymphoma and medullary carcinoma. In this case, we present the LELC of the breast in a 39 year-old woman with clinical, histological and immunohistochemical features with differential diagnosis.

The histopathological examination of the periprosthetic soft tissue and bone has contributed to the identification and description of the morphological features of adverse local tissue reactions (ALTR)/adverse reactions to metallic debris (ARMD). The need of a uniform vocabulary for all disciplines involved in the diagnosis and management of ALTR/ARMD and of clarification of the parameters used in the semi-quantitative scoring systems for their classification has been considered a pre-requisite for a meaningful interdisciplinary evaluation. This review of key terms used for ALTR/ARMD has resulted in the following outcomes: (a) pseudotumor is a descriptive term for ALTR/ARMD, classifiable in two main types according to its cellular composition defining its clinical course; (b) the substitution of the term metallosis with presence of metallic wear debris, since it cannot be used as a category of implant failure or histological diagnosis; (c) the term aseptic lymphocytic-dominated vasculitis- associated lesion (ALVAL) should be replaced due to the absence of a vasculitis with ALLTR/ALRMD for lymphocytic-predominant and AMLTR/AMRMD for macrophage-predominant reaction. This review of the histopathological classifications of ALTR/ARMD has resulted in the following outcomes: (a) distinction between cell death and tissue necrosis; (b) the association of corrosion metallic debris with adverse local lymphocytic reaction and tissue necrosis; (c) the importance of cell and particle debris for the viscosity and density of the lubricating synovial fluid; (d) a consensus classification of lymphocytic infiltrate in soft tissue and bone marrow; (e) evaluation of the macrophage infiltrate in soft tissues and bone marrow; (f) classification of macrophage induced osteolysis/aseptic loosening as a delayed type of ALTR/ARMD; (g) macrophage motility and migration as possible driving factor for osteolysis; (h) usefulness of the histopathological examination for the natural history of the adverse reactions, radiological correlation, post-marketing surveillance, and implant registries. The review of key terms used for the description and histopathological classification of ALTR/ARMD has resulted in a comprehensive, new standard for all disciplines involved in their diagnosis, clinical management, and long-term clinical follow-up. Cite this article: EFORT Open Rev 2021;6:399-419. DOI: 10.1302/2058-5241.6.210013

Kidney transplantation, like other transplants, has the risk of producing graft rejection due to genetic differences between donor and recipient. The three known types of renal rejection are listed in the Banff classification: T-cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR), and mixed rejection. The human leukocyte antigens (HLA) are highly polymorphic and may be the targets of donor-specific antibodies, resulting in ABMR. Therefore, prior to transplantation, it is necessary to analyze the HLA genotype of the donor and recipient, as well as the presence of DSA, in order to avoid hyperacute rejection. However, due to the shortage of kidneys, it is very difficult to find a donor and a recipient with completely matched HLA genotypes. This can trigger a future rejection of the kidney, as is reported in this work. We describe a patient who received a kidney transplant after a negative DSA test, who developed graft rejection with antibodies against the donor’s HLA-Bw4 public epitope and lymphocytic infiltrate four days after transplantation, whose differential diagnosis was mixed rejection.

Background Since the first report in 2008 of cases of anaplastic lymphoma kinase (ALK)-positive histiocytosis, originally described as a systemic, self-limiting disease in infants, the range of ALK-positive histiocytosis has been expanded to include localized diseases in older children and adults. Case presentation We present the case of an 18-year-old woman with a periumbilical painless mass for 5 months who underwent resection of the mass. Pathological examination showed that the tumour consisted predominantly of fascicular to storiform growth of nonatypical spindle cells admixed with lymphocytic infiltrates. The tumour spindle cells were diffusely positive for CD68, CD163 and ALK. Further molecular tests revealed an ALK gene fusion with Kinesin Family Member 5B (KIF5B) (E24)-ALK (E20), confirming ALK-positive histiocytosis. Follow-up at one and a half years after resection showed no tumour recurrence. Conclusion Remission of ALK-positive histiocytosis in local lesions can be achieved by complete resection, and clinical follow-up shows a favourable prognosis.

Disseminated histoplasmosis is a major cause of mortality in HIV-infected patients. Rapid and efficient diagnosis of Histoplasma capsulatum is crucial. Cytopathology is available in most hospitals and represents a rapid diagnostic alternative. In this study, we reviewed 12 years of experience to describe the cytology of histoplasmosis diagnosed by bronchoalveolar lavage (BAL) in relation to patient characteristics. BAL-diagnosed pulmonary histoplasmosis concerned 17 patients (14 HIV+). BAL cellularity ranged from 76,000 to 125,000 cells/mL in HIV patients, and 117,000 to 160,000 cells/mL in non-HIV patients. Macrophages predominated in all HIV patients (from 60% to 88%), lymphocytic infiltrates ranged from 5% to 15%, and neutrophils were very heterogeneous (from 2% to 32%). The number of H. capsulatum at hot spots seemed greater in HIV-infected than in immunocompetent patients (9 to 375 vs. 4 to 10) and were inversely proportional to the CD4 counts. Yeasts were both intracellular and extracellular in 85.7% of the HIV patients. This is the most comprehensive series detailing the cytological aspects of BAL in the diagnosis of H. capsulatum, focusing on the number of yeasts and their clustering pattern. The cytological examination of the Gomori-Grocott-stained BAL allows a reliable diagnosis of histoplasmosis.

Canine thymic epithelial tumours (TET) are uncommon and little is known about their behaviour. Previous attempts at histologic classification have varied, and as such reliable prognostic information is unavailable. The aim of this retrospective multi-institutional study was to evaluate cases of canine TETs, irrespective of subtype, in order to identify useful histopathologic and clinicopathologic prognostic factors. Cases were included if the tumour arose from the cranial mediastinum and a diagnosis of TET was made on the basis of histopathology. Fifty-one dogs were included. In addition to clinicopathologic data, histology samples were reviewed for the following features: mitotic count, percentage of necrosis, presence of Hassall's corpuscles, lymphocytic infiltrate, cellular pleomorphism and vascular or capsular invasion. The median survival time for all dogs was 449 days. The 1- and 2-year survival rate was 52.6% and 26.3% respectively. On multivariable analysis surgical excision of the thymic tumour was associated with significantly prolonged survival; the presence of metastasis, myasthenia gravis and moderate or marked cellular pleomorphism were associated with significantly reduced survival. Additional studies are needed to further evaluate prognostic factors to aid treatment recommendations.

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.

Reports of chilblain-like lesions (CLL) coinciding with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been described in the literature, but this phenomenon has not been critically summarized. The aim of this paper is to summarize reports of CLL coinciding with SARS-CoV-2 infection to clarify the prevalence, clinical relevance, and prognostic value of these lesions. A literature search was conducted using the Embase, Pubmed, and Scopus databases from December 2019 to June 16, 2020 using the search terms (“COVID-19” OR “coronavirus” OR “2019-nCoV” OR “SARS-CoV-2”) AND (“chilblain-like” OR “COVID toes” OR “acral”). Papers that described skin changes in patients with suspected or confirmed COVID-19 were included. A total of 31 papers were summarized, representing 813 cases of CLL. Available data suggests an equal gender distribution, mean age of 21 years, and median age of 14 years. Mild extracutaneous symptoms were reported in 53% of cases and 47% were asymptomatic. CLL occurred an average of 16 days after extracutaneous symptoms. Patients with CLL were positive for SARS-CoV-2 in 15% of cases. Lesions were mainly described as asymptomatic and/or pruritic erythematous to violaceous acral macules and plaques. Partial or complete resolution occurred in 85% of cases in a mean of 13 days. The most common histologic findings were perivascular and perieccrine superficial and deep lymphocytic infiltrates. Although a causal relationship between CLL and SARS-CoV-2 has not been confirmed, the temporal association and 15% positive SARS-CoV-2 rate in affected individuals should not be ignored.

The work was performed on experimental material. A model of hypothyroidism was obtained in 66 white rats, males of the Wistar strain, by thyroidectomy. Healthy rats aged 8–9 months weighing 250–300 g were selected for the experiment. The operation was performed under general anesthesia. Both thyroid lobes were removed. For histological examination, pieces of gland tissue were taken from both lobes. Pieces were fixed in a 10 % buffered formalin solution for 10 days, then histopreparations were prepared in the standard way. Histological examination revealed diffuse myxedema edema, severe vascular disorders (plethora, stasis, diapedetic hemorrhage), degenerative and destructive changes in hepatocytes, collicative necrosis, plasmolysis, the formation of cavities filled with edematous fluid, atrophy and thinning of the liver beams. When antioxidants α–tocopherol and mexidol are introduced in the postoperative period, stereotypic changes occur: myxedema, vascular disorders, dystrophic and destructive changes, lymphocytic infiltrates, however, these changes occur much later (on the 28th day), are focal in nature, the intensity of edema less pronounced, few lymphocytic infiltrates. When using antioxidants, an increase in reparative processes is observed: the multiplication of binuclear hepatocytes, the proliferation of fibroblasts with the formation of foci of sclerosis.

Pembrolizumab is a humanized monoclonal antibody that targets programmed cell death receptor-1. Stevens–Johnson syndrome (SJS) secondary to pembrolizumab has rarely been described in the treatment of malignant melanoma (MM). A 62-year-old woman developed a widespread bullous eruption following administration of her third dose of pembrolizumab for the treatment of MM. A skin biopsy showed sub-epidermal bulla formation with lymphocytic infiltrate and a necrotic roof, consistent with a SJS/toxic epidermal necrolysis (TEN) disorder. Intravenous methylprednisolone was administered. Upon cessation of oral prednisolone, there was a recrudescence of the eruption. A repeat skin biopsy confirmed recurrent SJS. Following a prolonged taper with oral prednisolone, there was no further relapse of SJS. Severe cutaneous adverse reactions such as SJS/TEN have been reported with pembrolizumab and can be associated with significant morbidity and even mortality. High-dose systemic corticosteroids are frequently used in its treatment. Concerns about the potential negative effect of high-dose steroids have re-surfaced, given the observed reduced overall survival in patients with MM. Due to difficulties in performing studies in this population, the benefits and risk of steroids should be considered on a case-by-case basis.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare vascular tumor which presents as a dermal papule or a nodule over the head-and-neck region. Histopathologically, there is vascular proliferation in the upper dermis and diffuse lymphocytic infiltrate with eosinophilia. Kimura's disease is the closest differential of ALHE, which presents as subcutaneous nodules. We report a case of ALHE presenting with a violaceous papule overlying a subcutaneous nodule, histopathologically; both lesions were diagnosed as ALHE.

Granulomatous pigmented purpuric dermatosis clinically manifests as hyperpigmented maculae and petechiae, predominantly on the lower extremities. Histopathologically, it is characterized by a lymphocytic infiltrate in the upper dermis, extravasated erythrocytes, and hemosiderin deposits. There is an infrequent variant called granulomatous pigmented purpuric dermatosis, which histologically is characterized by the presence of non-necrotizing granulomas associated with the classic findings of other pigmented purpuric dermatoses. It more frequently affects middle-aged women of Asian origin, and predominantly on the lower extremities. The authors present the case of a female patient with granulomatous pigmented purpuric dermatosis on the lower extremities with blaschkoid distribution.

Background/aims T-cell acute lymphoblastic leukemia (T-ALL) is an uncommon, aggressive malignancy that rarely presents in the skin and is generally not considered as part of the differential diagnosis by dermatologists and dermatopathologists. We describe an unusual case of T-ALL presenting with folliculocentric, erythematous papules on the face, histologically resembling mycosis fungoides (MF). Immunostaining for terminal deoxynucleotidyl transferase (TdT) was positive in tumor cells, supporting the diagnosis of cutaneous involvement by T-ALL. TdT is a nuclear enzyme expressed by immature lymphoid malignancies, but the expression pattern of this marker is not well characterized in the skin. We aimed to assess TdT staining in skin biopsies with similar-appearing lymphocytic infiltrates. Methods We evaluated the immunostaining profile of TdT in a cohort of 23 patients, including 13 cases of MF and 10 cases of spongiotic dermatitis. Results The lymphocytes in the MF and spongiotic dermatitis cases lacked nuclear staining for TdT. Nonspecific, granular, cytoplasmic staining was observed in a small number of background cells. Conclusions TdT may assist dermatopathologists in discriminating malignant infiltrates of T-ALL from other conditions.

Rosai-Dorfman disease (RDD) is an uncommon disorder, characterized by an atypical expansion of histiocytes which classically shows emperipolesis and immunoreactivity with S-100 protein. RDD affects the lymph nodes as well as extranodal sites; however, RDD of the breast is exceptionally rare. Herein, we describe the histopathologic features of 22 cases of RDD occurring in the breast, with an emphasis on the differential diagnosis. All cases were notable for an exuberant lymphocytic infiltrate with and without germinal center formation, and the majority (19/22) showed numerous plasma cells: 5 to 132/high-power field (HPF). IgG and IgG4 immunohistochemical stains were available for 13 cases; in no instance were criteria for IgG4-related sclerosing disease met, though in a single case the IgG4/IgG ratio was increased to 25%. Sclerosis was present in the majority of cases (18/22), and was frequently prominent. RDD cells showing emperipolesis were present in all cases (22/22), and ranged from rare (1/50 HPF) to numerous (50/50 HPF). Two of the cases in our series were initially misdiagnosed as inflammatory myofibroblastic tumor and plasma cell mastitis with granulomatous inflammation. As emperipolesis can be indistinct, the presence of stromal fibrosis and a prominent lymphoplasmacytic inflammatory infiltrate should prompt a careful search for the characteristic histiocytes, which can be aided by the use of S-100 immunohistochemistry.