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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.

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.

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.

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.

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.

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.

Background Approximately two thirds of patients with localized triple-negative breast cancer (TNBC) harbor residual disease (RD) after neoadjuvant chemotherapy (NAC) and have a high risk-of-recurrence. Targeted therapeutic development for TNBC is of primary significance as no targeted therapies are clinically indicated for this aggressive subset. In view of this, we conducted a comprehensive molecular analysis and correlated molecular features of chemorefractory RD tumors with recurrence for the purpose of guiding downstream therapeutic development. Methods We assembled DNA and RNA sequencing data from RD tumors as well as pre-operative biopsies, lymphocytic infiltrate, and survival data as part of a molecular correlative to a phase II post-neoadjuvant clinical trial. Matched somatic mutation, gene expression, and lymphocytic infiltrate were assessed before and after chemotherapy to understand how tumors evolve during chemotherapy. Kaplan-Meier survival analyses were conducted categorizing cancers with TP53 mutations by the degree of loss as well as by the copy number of a locus of 18q corresponding to the SMAD2, SMAD4, and SMAD7 genes. Results Analysis of matched somatic genomes pre-/post-NAC revealed chaotic acquisition of copy gains and losses including amplification of prominent oncogenes. In contrast, significant gains in deleterious point mutations and insertion/deletions were not observed. No trends between clonal evolution and recurrence were identified. Gene expression data from paired biopsies revealed enrichment of actionable regulators of stem cell-like behavior and depletion of immune signaling, which was corroborated by total lymphocytic infiltrate, but was not associated with recurrence. Novel characterization of TP53 mutation revealed prognostically relevant subgroups, which were linked to MYC-driven transcriptional amplification. Finally, somatic gains in 18q were associated with poor prognosis, likely driven by putative upregulation of TGFß signaling through the signal transducer SMAD2. Conclusions We conclude TNBCs are dynamic during chemotherapy, demonstrating complex plasticity in subclonal diversity, stem-like qualities, and immune depletion, but somatic alterations of TP53/MYC and TGFß signaling in RD samples are prominent drivers of recurrence, representing high-yield targets for additional interrogation. Electronic supplementary material The online version of this article (10.1186/s13058-019-1171-7) contains supplementary material, which is available to authorized users.

Sjogren's syndrome is a chronic autoimmune disorder of the exocrine glands with associated lymphocytic infiltrates of the affected glands. Dryness of the mouth and eyes results from involvement of the salivary and lacrimal glands. Up to one-half of affected individuals also develop extraglandular involvement in organs distinct from the salivary and lacrimal glands, including the joints, skin, lung, gastrointestinal tract, nervous system, and kidneys. The disease also occurs in conjunction with other autoimmune disorders, such as systemic lupus erythematosus and rheumatoid arthritis. We report a case of a 76-year-old woman who presented to our department with a swelling on the left cheek. Investigations revealed Sjogren's syndrome as the underlying cause of the facial tumor.

Erythroderma consists of erythema and scaling involving most or all of the body surface. This generalized eruption may be idiopathic, drug-induced or secondary to cutaneous or systemic disease. A 71-year-old man is reported presenting generalized erythema and desquamation with deck-chair sign, nail dystrophy, and plantar ulcers associated with loss of local tactile sensitivity. Biopsies from three different sites demonstrated diffuse lymphocytic infiltrate with incipient granulomas. Fite-Faraco staining showed numerous isolated bacilli and globi. The skin smear was positive. Clinical and pathological diagnosis of borderline lepromatous leprosy was confirmed. This report demonstrates that chronic multibacillary leprosy can manifest as erythroderma and thus should be included in the differential diagnosis.

Objective: Triple negative breast cancer (TNBC), despite being the uncommon subtype, contributes a major portion to mortality and associated with poor prognosis. The purpose of this study was to evaluate the cytological criteria for the diagnosis of TNBC through fine-needle aspiration cytology (FNAC). Material and Method: Clinical, cytological, histological, and immunohistochemical (IHC) data of 256 patients were evaluated, and patient were classified as TNBC and non-TNBC phenotype by IHC. All cytological specimens were reviewed for 12 criteria: cellularity, tubule/gland formation, syncytial clusters, large bare nuclei, nuclear atypia, chromatin pattern, cell borders, nucleolus, cytoplasm, lymphocytic infiltrate, calcification, and necrosis. The Fischer's exact test was used to show test association. Result: Out of 256 patients, 82 patients were TNBC, and 174 patients were non-TNBC. TNBC phenotype showed statistically significant association to cellularity, tubule/gland formation, syncytial cluster formation, bare nuclei, nuclear atypia, cell borders, lymphocyte infiltration, and necrosis. Conclusion: FNAC can be helpful in making diagnosis of TNBC and along with ER, PR, HER2 characterization, helpful in planning treatment strategy, saving time, manpower, and resources in the patient management.

Basal-like breast cancer (BLBC) is characterized by high grade, high mitotic indices, presence of central necrotic or fibrotic zones, and lymphocytic infiltrate. Patients presenting with BLBC have a poor prognosis and a short-term disease-free and overall survival. BLBCs may include different histological types of breast cancers but the most common histological type is represented by invasive ductal carcinomas of no special type (IDC-NST). Typical immunohistochemical markers for these tumors are basal-type cytokeratin markers such as CK5/6, CK14, CK17, but several BLBCs also express luminal-type CKs, such as CK8/18, CK19. Different molecular alterations, including BRCA1 dysfunction, p53 mutations, up-regulation of EGFR, inactivation of PTEN and the aberrant expression of many non-coding RNAs molecules are detected in BLBC cells suggesting the possibility of defining new targeted therapeutic strategies for this tumor type.

Background: Oral lichen planus (OLP) is characterized histologically by epithelial basal cell destruction and a dense subepithelial lymphocytic infiltrate. Mast cells (MCs) play a role in the pathogenesis and progression of the disease causing changes in the basement membrane (BM). BM is seen as continuous or fragmented, distinct or indistinct, and afibrillar or fibrillar extensions. Aims and Objectives: This study was done to demonstrate the BM using acriflavine stain in addition to hematoxylin and eosin (H-E) stain. An attempt was also made to study MC using Azure A stain and assess the degree of changes in the thickness of BM associated with degranulated MC in patients with OLP. Materials and Methods: A total of 66 paraffin-embedded tissue sections which included 30 inflamed gingival mucosa (IGM) and 36 OLP were stained with H-E stain, Azure A, and fluorescent periodic acid–acriflavine stain. Results: MC density was higher in OLP when compared with MC in IGM. Degranulated MCs were found in abundance in OLP. Thickness of BM was significantly less in OLP when compared with IGM. Significant fragmentation was seen in OLP when compared with BM of IGM. Conclusion: Degranulated MC in OLP may or may not alter the quality of BM but definitely seems to influence the thickness of the BM both directly and indirectly.

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.

In this systematic review, we anticipated in summarizing clinical features, histopathological hallmarks, and possible pathology behind the maculopapular skin eruptions occurring in Covid‐19 patients. A literature search was executed using MEDLINE/PubMed and Embase databases for articles published till 20 November 2020. All eligible articles including observational studies, case reports, and case series reporting the maculopapular skin lesion in Covid‐19 patients were included. Data were obtained for 354 Covid‐19 patients presenting with maculopapular lesions from 40 studies. The mean age of these patients was 53 years, and with 42% of them being male. These maculopapular lesions differed considerably in terms of distribution and appearance, ranging from diffuse erythematous maculopapular lesions to scattered erythematous macules coalescing into papules to maculopapular lesions in plaques. The mean duration of the lesion was 8 days. These lesions were frequently localized on trunks and extremities. Superficial perivascular dermatitis with lymphocytic infiltrate was a histopathological hallmark of these lesions. As these skin lesions may have a possible association with diagnosis, management, prognosis, and severity of the disease, all health practitioners need to be well acquainted with these Covid‐19 skin lesions. Also, in the middle of this worldwide pandemic, early identification of this eruption may help manage this infection's further spread.

Background : Encephalitozoonosis is caused by the protozoan Encephalitozoon cuniculi , in rabbits, and can affect humans. The disease can be fatal and difficult to diagnose. It can be asymptomatic or cause vestibular neurological disease, paralysis, uveitis in addition to chronic kidney disease in rabbits. The transmission of the microorganism's spores occurs by ingestion, inhalation, or by the transplacental route. The aim of this work is to report a case of encephalitozoonosis in a pet rabbit ( Oryctolagus cuniculus ). Case : An Oryctolagus cuniculus with a history of paraparesis of the thoracic and pelvic limbs was referred for necropsy, the evolution of the clinical picture happened in one day. After death, a necropsy was performed. Organ fragments were collected, fixed, and processed routinely for histology. Macroscopically, there was evidence of hepatic lobes, without injury to the other organs. Microscopically it was observed in the white and gray substance of the telencephalon multiple circumscribed granulomas composed of a necrotic center surrounded by macrophages, giant multinucleated cells in addition to lymphocytes and plasmocytes in the periphery, delimited by fibrous connective tissue. Around the vessels, perivascular cuffs with two to four layers of lymphocytic infiltrate were observed. Besides, special staining of Schiff's Periodic Acid (PAS) and Ziehl-Neelsen was performed, in which numerous cylindrical, eosinophilic structures of approximately 2.5 x 1.0 µm were observed, compatible with E. cuniculi spores. Besides, histiocytic lymphoblasts pericoronitis was noted in the liver. There were no relevant changes in the kidney. Discussion : The diagnosis of encephalitozoonosis in rabbits was based on clinical and anatomopathological findings. Tetraparesis was the predominant sign in the present case and was justified by telencephalic lesions. This clinical sign is included in the literature but is less common than the syndrome such as head tilt and paralysis. The diagnosis of the disease is usually made by post-mortem examination when it is possible to identify the spores in the lesions. Multifocal granulomatous encephalitis was the most significant finding in this case, which is also consistent with other studies. The pathogenesis of granulomatous lesions is still controversial. It is known that spores allow phagocytosis by macrophages, which induce the production of interleukins and other cytokines by TCD4 + lymphocytes, thereby activating the action of TCD8 + (cytotoxic) lymphocytes. Natural killer cells, granulocytes, other macrophages, and B lymphocytes are also recruited. Although there is such an inflammatory response, the antibodies produced are not efficient to eliminate the agent from the host organism, however, they contribute to the process of opsonization and consequent phagocytosis, facilitating the destruction of the microsporidium by macrophages. The neurological form was predominant in this case, with no chronic or ocular renal forms, possibly due to the rapid clinical evolution. Special stains were useful for visualizing intralesional spores. Although PAS staining is considered to be of little use, it was relevant in this case. The visualization of the agent made it possible to distinguish differential diagnoses, among them vestibular syndrome secondary to otitis due to pasteurellosis, toxoplasmosis, neoplasms, traumas, or diseases of the spine. Thus, a diagnosis of encephalitozoonosis was made in a rabbit through clinical and anatomopathological correlation using Ziehl-Neelsen and PAS stains. Keywords : granuloma, Encephalitozoon cuniculi , central nervous system. Descritores : granuloma, Encephalitozoon cuniculi, sistema nervoso central. Titulo: Encefalitozoonose em coelho ( Oryctolagus cuniculus )

Background: Cutaneous melanoma shows high variability regarding clinicopathological presentation, evolution and prognosis. Methods: Next generation sequencing was performed to analyze hotspot mutations in different areas of primary melanomas (MMp) and their paired metastases. Clinicopathological features were evaluated depending on the degree of variation of the BRAFV600E mutant allele frequency (MAF) in MMp. Results: In our cohort of 14 superficial spreading, 10 nodular melanomas and 52 metastases, 17/24 (71%) melanomas had a BRAFV600E mutation and 5/24 (21%) had a NRASQ61 mutation. We observed a high variation of BRAFV600E MAF (H-BRAFV600E) in 7/17 (41%) MMp. The H-BRAFV600E MMp were all located on the trunk, had lower Breslow and mitotic indexes and predominantly, a first nodal metastasis. Regions with spindled tumor cells (Spin) and high lymphocytic infiltrate (HInf) were more frequent in the H-BRAFV600E patients (4/7, 57%), whereas regions with epithelial tumor cells (Epit) and low lymphocytic infiltrate (LInf) were predominant (6/10, 60%) and exclusive in the low BRAFV600E MAF variation tumors (L-BRAFV600E). The H-BRAFV600E/Spin/HInf MMp patients had better prognostic features and nodal first metastasis. Conclusions: The H-BRAFV600E MMp were located on the trunk, had better prognostic characteristics, such as lower Breslow and mitotic indexes as well as high lymphocytic infiltrate.

Actinic cheilitis (AC) is a oral disorder potentially malignant with dysplastic proliferations of keratinocytes. The lesion has a predilection for the red zone of the lower lip and may be closely related to excessive exposure to sunlight. The aim of this study was to report a clinical case of AC in a cardiac patient, admitted to the intensive care unit. Male patient, leucoderma, 82 years old, with a whitish lesion on the red zone of the lower lip, pedicled and sessile areas, well-marked limits and irregular shape. The incisional biopsy was performed in the intensive care unit bed and sent to the laboratory of pathological analysis in the State of Paraíba (LACEN). Microscopy showed an epidermis thickened by acanthosis, with cells showing nuclear pleomophism and hyperchromism. In the dermis, the presence of vascular ectasia, diffuse lymphocytic infiltrate and basophilic degeneration of elastic fibers, areas with foci of superficial erosion of the lining epithelium covered by a crust of necrotic and fibrinoleucocytic material were also observed. The anatomopathological diagnosis was ulcerated actinic cheilitis. The treatment performed was total surgical excision with monitoring of the healing process until the patient's hospital discharge. It was concluded that the treatment proposed to the patient was decisive. Also the presence of the dentist in a hospital environment facilitated the access and treatment of a oral disorder potentially malignant, favoring the prognosis of the case. La queilitis actínica (QA) es un trastorno oral potencialmente maligno con proliferaciones displásicas de queratinocitos. La lesión tiene predilección por la zona roja del labio inferior y puede estar estrechamente relacionada con la exposición excesiva a la luz solar. El objetivo de este estudio fue reportar un caso clínico de QA en un paciente cardíaco ingresado en la unidad de cuidados intensivos. Paciente masculino, leucodermia, 82 años, con lesión blanquecina en zona roja del labio inferior, zonas pediculadas y sésiles, bordes afilados y forma irregular. La biopsia incisional se realizó en la cama de la unidad de cuidados intensivos y se envió al laboratorio de análisis patológico en el Estado de Paraíba (LACEN). La microscopía mostró una epidermis engrosada por acantosis, con células con pleomofismo nuclear e hipercromismo. En la dermis también se observó la presencia de ectasia vascular, infiltrado linfocítico difuso y degeneración basófila de fibras elásticas, áreas con focos de erosión superficial del epitelio de revestimiento recubierto por una costra de material necrótico y fibrinoleucocítico. El diagnóstico anatomopatológico fue queilitis actínica ulcerada. El tratamiento realizado fue la exéresis quirúrgica total con seguimiento del proceso de cicatrización hasta el alta hospitalaria del paciente. Se concluyó que el tratamiento propuesto al paciente fue determinante y que la presencia del odontólogo en un entorno hospitalario facilitó el acceso y tratamiento de un trastorno oral potencialmente maligno, favoreciendo el pronóstico del caso. A Queilite Actínica (QA) é uma desordem oral potencialmente maligna com proliferações displásicas de queratinócitos. A lesão tem predileção pela zona vermelha do lábio inferior e pode estar intimamente relacionada com exposição excessiva à luz solar. O objetivo deste estudo foi de relatar um caso clínico de QA em paciente cardiopata, internado em unidade de terapia intensiva. Paciente do sexo masculino, leucoderma, 82 anos, com lesão na zona vermelha do lábio inferior de cor esbranquiçada, áreas pediculadas e sésseis, limites nítidos e formato irregular. A biópsia incisional foi realizada em leito da unidade de terapia intensiva e enviada ao laboratório de análise patológica do Estado da Paraíba (LACEN). A microscopia apresentou uma epiderme espessada por acantose, com células apresentando pleomofismo e hipercromismo nuclear. Na derme presença de ectasia vascular, infiltrado linfocitário difuso e degeneração basófila de fibras elásticas, ainda foram observadas áreas com focos de erosão superficial do epitélio do revestimento recobertos por crosta de material necrótico e fibrinoleucocitário. O diagnóstico anatomopatológico foi de queilite actínica ulcerada. O tratamento realizado foi a excisão cirúrgica total com acompanhamento do processo de cicatrização até a alta hospitalar do paciente. Concluiu-se que o tratamento proposto ao paciente foi resolutivo e que a presença do cirurgião dentista em ambiente hospitalar facilitou o acesso e tratamento de uma desordem oral potencialmente maligna, favorecendo o prognóstico do caso.

Purpose For optimal management of ductal carcinoma in situ (DCIS), reproducible histopathological assessment is essential to distinguish low-risk from high-risk DCIS. Therefore, we analyzed interrater reliability of histopathological DCIS features and assessed their associations with subsequent ipsilateral invasive breast cancer (iIBC) risk. Methods Using a case-cohort design, reliability was assessed in a population-based, nationwide cohort of 2767 women with screen-detected DCIS diagnosed between 1993 and 2004, treated by breast-conserving surgery with/without radiotherapy (BCS ± RT) using Krippendorff’s alpha (KA) and Gwet’s AC2 (GAC2). Thirty-eight raters scored histopathological DCIS features including grade (2-tiered and 3-tiered), growth pattern, mitotic activity, periductal fibrosis, and lymphocytic infiltrate in 342 women. Using majority opinion-based scores for each feature, their association with subsequent iIBC risk was assessed using Cox regression. Results Interrater reliability of grade using various classifications was fair to moderate, and only substantial for grade 1 versus 2 + 3 when using GAC2 (0.78). Reliability for growth pattern (KA 0.44, GAC2 0.78), calcifications (KA 0.49, GAC2 0.70) and necrosis (KA 0.47, GAC2 0.70) was moderate using KA and substantial using GAC2; for (type of) periductal fibrosis and lymphocytic infiltrate fair to moderate estimates were found and for mitotic activity reliability was substantial using GAC2 (0.70). Only in patients treated with BCS-RT, high mitotic activity was associated with a higher iIBC risk in univariable analysis (Hazard Ratio (HR) 2.53, 95% Confidence Interval (95% CI) 1.05–6.11); grade 3 versus 1 + 2 (HR 2.64, 95% CI 1.35–5.14) and a cribriform/solid versus flat epithelial atypia/clinging/(micro)papillary growth pattern (HR 3.70, 95% CI 1.34–10.23) were independently associated with a higher iIBC risk. Conclusions Using majority opinion-based scores, DCIS grade, growth pattern, and mitotic activity are associated with iIBC risk in patients treated with BCS-RT, but interrater variability is substantial. Semi-quantitative grading, incorporating and separately evaluating nuclear pleomorphism, growth pattern, and mitotic activity, may improve the reliability and prognostic value of these features.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare CD4+/CD56+ hematological malignancy with aggressive clinical course and poor prognosis. Histologically, BPDCN is characterized by a diffuse, monomorphous infiltration of cutaneous, subcutaneous, and sometimes other tissues such as lymph nodes and bone marrow, by medium-sized neoplastic cells with blastoid morphology. Typically, there is absence of lymphocytic infiltrate. Diagnosis relies on immunophenotypic expression of CD4, CD56, and the more specific markers of plasmacytoid dendritic cells CD123, CD303/BDCA2, and TCL1. We report a case of a 57-year-old man who presented a 4 cm-long solitary, erythemateous lesion on the right cheek, corresponding to a BPDCN but initially misdiagnosed as T-cell lymphoma. The case was characterized by conservation of skin appendages and a diffuse T-cell infiltrate, which strongly expressed PD1. ETV6 and MYC fluorescent in situ hydridization and next-generation sequencing were performed on this tumor. The main difficulties to diagnose BPDCN were the atypical cytology of tumor cells and their CD4 and CD43 expression, as can be seen in T-cell lymphomas. The diffuse T-cell infiltrate was also challenging. The patient is still alive 29 months after diagnosis, suggesting a potential prognostic impact of T-cell infiltration and the absence of MYC translocation. The presence of TET2 and ASXL1 mutations supporting BPDCN and reinforcing the hypothesis of a myeloid origin.

Insulitis is a characteristic inflammatory lesion consisting of immune cell infiltrates around and within the pancreatic islets of patients with recent-onset type 1 diabetes (T1D). The infiltration is typically mild, both in terms of the number of infiltrating cells and the number of islets affected. Here, we present an unusual histopathological case study of a 66-year-old female patient with long-standing T1D, insulitis, and islet-associated lymphoid tissue. Most islets in the head of the pancreas of this patient were insulin-deficient, whereas the islets in the tail appeared normal. Insulitis was present in 0.84% of the insulin-containing islets and three islets had large lymphocytic infiltrates resembling tertiary lymphoid structures (TLS). Of note, this is the first description of potential TLS in the endocrine pancreas of a patient with T1D. Their association with a marked residual beta cell mass is of interest and may hint at new insights into disease progression and regulation of autoimmunity. Electronic supplementary material The online version of this article (10.1007/s00428-020-02915-4) contains supplementary material, which is available to authorized users.

Here, we report the pathological findings of nine complete autopsies of individuals who died in community settings in the UK, three of which were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), three tested negative for SARS-CoV-2 but are likely false negatives, and three died of other respiratory infections. Autopsy revealed firm, consolidated lungs or lobar pneumonia. Histology of the lungs showed changes of diffuse alveolar damage with fibrin membrane formation, thickened alveolar walls and interstitium with lymphocytic infiltrate, and type 2 pneumocyte hyperplasia with shedding into the alveolar space. This series is the first in the world to describe autopsy findings in individuals dying suddenly in the community, not previously known to have COVID-19 infection, and the first autopsy series in the UK. During a time when testing in the UK is currently primarily offered to patients in hospital or symptomatic key workers, with limited testing available in community settings, it highlights the importance of testing for COVID-19 at autopsy. Two deaths occurred in care homes where a diagnosis of COVID-19 allowed the health protection team to provide support in that ‘closed setting’ to reduce the risks of onward transmission. This work highlights the need for frequent COVID-19 testing in the management of patients in community settings. Comprehensive virology and microbiology assessment is pivotal to correctly identify the cause of death, including those due to COVID-19 infection, and to derive accurate death statistics.

En coup de sabre morphea is a clinical variant of morphea, presenting as a linear depressed, atrophic area in the paramedian forehead or the frontoparietal scalp, resembling a stroke from a sword. It affects the skin and subcutaneous connective tissues, with possible extension to the underlying musculature, cartilage, and bone and variable association with neurologic symptoms. A 50-year-old woman presented to our clinic for evaluation of an atrophic lesion on her forehead and scalp appearing 1 year before, progressively extending over time. An alopecic atrophic area involving the skin and subcutaneous tissues of her right forehead and scalp arranged in a linear fashion with an “en coup de sabre” appearance was observed in relation with hair loss in the affected area. Reflectance confocal microscopy showed marked hyperreflective areas with severe eccrine gland atrophy. All sebaceous glands had disappeared, with sporadic follicular persistence reduction. Histopathological examination of a punch biopsy specimen taken from a central parietal alopecic area was consistent with a diagnosis of morphea. To our knowledge, this is the first report regarding the use of reflectance confocal microscopy as an ancillary diagnostic technique in linear localized morphea of the scalp and face. This noninvasive technique may represent a useful tool in distinguishing between early stages of the disease, with prevalence of inflammatory lymphocytic infiltrate, and late stages characterized by more prominent sclerosis with mild or absent signs of inflammation.

We present a 50-year-old woman with human immunodeficiency virus admitted to the hospital for melenic stools and anemia who underwent esophagogastroduodenoscopy for evaluation of upper gastrointestinal bleed. She is found to have inflammation of the esophagus with ulcerations and crater formation. A biopsy reveals severe inflammation with lymphocytic infiltrates with civatte bodies suggestive of lichenoid esophagitis with the presence of spirochetes (Treponema pallidum). The presence of syphilis in the esophagus causing lichenoid esophagitis is an extremely rare presentation that has never been reported.

Tumid lupus erythematosus (TLE) is a rare form of chronic cutaneous lupus that has triggered much debate regarding its clinical and histopathological features. It has been classically defined as annular erythematous, succulent, plaques involving the face and trunk that typically are devoid of any papulosquamous features such as scale and follicular plugging. These lesions are a clinical mimicker of other urticarial lesions such as urticarial vasculitis and lymphocytic infiltrate of Jessner. We report a case of TLE presenting in a 49-year-old Caucasian female whose initial clinical presentation was concerning for urticarial vasculitis due to presence of urticarial-like lesions present for approximately three months. Laboratory studies and histopathological correlations confirmed the diagnosis of TLE and the patient was successfully treated with topical corticosteroids.

In melanoma, the lymphocytic infiltrate is a prognostic parameter classified morphologically in “brisk”, “non-brisk” and “absent”. The meaning of “brisk” is “active, energetic”, implying a functional connotation which has never been proved. Recently, it has been shown that not all brisk infiltrates have a good prognosis, that lymphocytic populations can be very heterogeneous, and that anti-PD-1 immunotherapy supports activated T cells. Here, we characterize the immune landscape in primary melanoma by high-dimensional single cell multiplex analysis in tissue sections (MILAN technique) followed by image analysis, RT-PCR and shotgun proteomics. We observed that the brisk and non-brisk patterns of tumor infiltrating lymphocytes (TILs) in primary melanoma are heterogeneous functional categories that can be further sub-classified according to the functional status of their lymphocytes as active, transitional or exhausted. We found that only activation of TILs correlates with spontaneous regression, and that the good prognosis of melanomas with a brisk pattern could be due to the fact that in these case the Tcy that are in contact with the melanoma cells are still active, and consequently the melanoma is still under immune control at the moment of surgical excision. The main inflammatory cell subpopulations that are present in the microenvironment associated with activation and exhaustion and their spatial relationships are described using neighbourhood analysis. Finally, we show a bioinformatic pipeline that, starting from common immunofluorescence stainings, can transform the tissue into a digitalized image, which represents the starting point for multiple deeper levels of analysis.

Our aim is to complement observer-dependent approaches of immune cell evaluation in microscopy images with reproducible measures for spatial composition of lymphocytic infiltrates. Analyzing such patterns of inflammation is becoming increasingly important for therapeutic decisions, for example in transplantation medicine or cancer immunology. We developed a graph-based assessment of lymphocyte clustering in full whole slide images. Based on cell coordinates detected in the full image, a Delaunay triangulation and distance criteria are used to build neighborhood graphs. The composition of nodes and edges are used for classification, e.g. using a support vector machine. We describe the variability of these infiltrates on CD3/CD20 duplex staining in renal biopsies of long-term functioning allografts, in breast cancer cases, and in lung tissue of cystic fibrosis patients. The assessment includes automated cell detection, identification of regions of interest, and classification of lymphocytic clusters according to their degree of organization. We propose a neighborhood feature which considers the occurrence of edges with a certain type in the graph to distinguish between phenotypically different immune infiltrates. Our work addresses a medical need and provides a scalable framework that can be easily adjusted to the requirements of different research questions., Author summary In this study, we developed a workflow to detect and classify immune infiltrates in giga-pixel microscopy images. It allowed us to measure the degree of organization in lymphocyte clusters with graph-based features and finally to distinguish between tertiary lymphoid organs and other infiltrates. As a clinically relevant use case, we applied it to three different types of tissues and diseases. Our method addresses the need for observer-independent, large-scale evaluation of immune cell patterns and is a prerequisite to capture spatial composition of immune cells that can be used to parameterize mathematical models in systems immunology.

Diabetic mastopathy is a rare benign breast condition. It is strongly associated with type I diabetes mellitus and commonly presents similar to malignancy. Here, we report a case of a 29-year-old Saudi female with a long history of type I diabetes mellitus (DM) who presented with a painless hard breast mass and had a strong family history of breast cancer. Further evaluation with ultrasound (US) imaging revealed a highly suspicious, ill-defined hypoechoic lesion. Mammographic examination revealed that both breasts were of normal shape with bilateral dense glandular parenchyma. US-guided true-cut biopsy was carried out, which showed acellular fibro-sclerotic tissues with normal-looking lobules and ducts surrounding by a dense lymphocytic infiltrate. Subsequently, a diagnosis of diabetic mastopathy was established. Results were discussed with the patient, and an agreement was reached to proceed with an excisional biopsy for further reassurance and exclusion of malignancy. Local surgical excision of the lesion was performed and histopathological examination revealed extensive fibrosis of the specimen with no cellular atypia. Awareness of such a condition, with its clinical, radiographical, and histopathological characteristics, is essential in order to alleviate the patient's anxiety and avoid unnecessary surgical interventions.

Made available in DSpace on 2020-12-12T01:59:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 Focal eosinophilic myositis (FEM) is a rare disease that is even more uncommon in affecting the periocular area. The authors are reporting the first case of FEM occurring in the lower eyelid of a 45-year-old Caucasian female who presented with localized painful area of glossy induration and peau d'orange skin lesion. Magnetic resonance image shows significant hyperintense thickening of the pre-septal orbicularis muscle region on T2-weighted images. Incisional biopsy of the induration revealed marked fibrinoid degeneration of the orbicularis muscle and adjacent fascia, mixed cellular infiltration of lymphocytes and eosinophils and a predominant CD8+ lymphocytic infiltrates in the immunohistochemical study. The final diagnosis was FEM. Department of Ophthalmology Rio Hortega University Hospital Department of Pathology Rio Hortega University Hospital Department of Internal Medicine Rio Hortega University Hospital Department of Ophthalmology Faculdade de Medicina de Botucatu-UNESP Department of Ophthalmology Faculdade de Medicina de Botucatu-UNESP

Background Cardiac myxomas, the most common primary cardiac tumors, are generally benign neoplasms. Primary cardiac lymphoma is a rare cardiac malignancy with a very poor prognosis. Here we present a case of a cardiac myxoma with cerebral metastases and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) arising within the cerebral metastases. Case description A 62-year-old man, who presented with symptoms of multiple transient ischemic attacks, was found to have a left atrial myxoma. Twelve months after excision of the myxoma, the patient experienced a recurrence of neurologic symptoms. Brain magnetic resonance imaging revealed multiple hemorrhagic masses. Craniotomy was performed to resect the lesions. Histopathologic examination confirmed cardiac myxoma metastases and a small lymphocytic infiltrate within the tumor consistent with CLL/SLL. Conclusion Including the present case, there are 27 cases of cardiac myxoma cerebral metastases and 22 cases of lymphomas arising within myxomas. The present case is the first known instance of both entities in the same patient. There is no standard management for either cardiac myxoma metastases or lymphoma within a myxoma. For both diseases, surgical excision is the primary treatment modality, but postoperative chemotherapy and/or radiation have been attempted. Myxomas may create a chronic inflammatory state that could lead to the development of CLL/SLL.

We wanted to evaluate the prognostic value of common histopathological variables in a large cohort of patients with cancer in the mobile tongue as such information can be important for treatment stratification of the individual patient, especially for patients with low-stage disease. In addition, we wanted to investigate whether an alternative scoring model with fewer options would compromise the prognostic value. One hundred fifty patients with oral tongue squamous cell carcinomas that were treated in curative intent and with available HE-stained tumor sections were included. We reclassified all tumors and performed univariate and multivariate survival analyses of histopathological and clinical variables. For the complete cohort, lymph node status, grade of differentiation, perineural infiltration, and lymphocytic infiltration were independent prognosticators. In the low-stage disease group, independent prognostic factors were tumor size, grade of differentiation, and lymphocytic infiltrate. For patients with low-stage disease, a histo-score combining the scores for tumor differentiation and lymphocytic infiltrate identified a group of patients with particularly low survival, as patients with moderately or poorly differentiated tumors and little lymphocytic infiltrate had a less favorable 5-year survival outcome than patients in the high-stage disease group. This study shows that a histo-score combining tumor differentiation and lymphocytic infiltration should be given special consideration in treatment planning. Our results also illustrate that many variables can be scored with fewer options than previously suggested to increase their reproducibility, and still maintain their prognostic value. Electronic supplementary material The online version of this article (10.1007/s00428-020-02875-9) contains supplementary material, which is available to authorized users.

Background Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an increasingly recognized neuroinflammatory syndrome that predominantly affects the pontine and cerebellar brain structures. Characteristically, patients will develop glucocorticoid-responsive brainstem disorders, demonstrate pontocerebellar contrast enhancement on magnetic resonance imaging (MRI), and exhibit an angiocentric, lymphocytic infiltrate in brain biopsies. We have presented and discussed 2 novel and challenging cases of CLIPPERS syndrome to highlight the clinical and radiological diversity of the syndrome. Case Description The first case was of a 66-year-old male patient who had presented with dizziness, headaches, gait disturbances, mild cognitive impairment, and visual field loss to the left side. MRI revealed 1 cerebellar and 2 occipital contrast-enhancing lesions that were suspicious for intracerebral metastases. The second case was of a 53-year-old male patient who had presented with temporal lobe epilepsy, anomic aphasia, and mild cognitive impairment. MRI demonstrated 4 contrast-enhancing lesions in the pons, temporal lobe, and thalamus that were suspicious for intracerebral lymphoma. Because of the radiological presentation, neoplastic disease was the most plausible diagnosis for both patients. However, repeated biopsies ruled out tumor manifestation, and the findings were finally consistent with CLIPPERS syndrome. The significant and long-lasting response to immunosuppressive treatment confirmed the diagnosis. Conclusions In both cases, the characteristics of CLIPPERS syndrome imitated malignant tumor growth. This scenario can be challenging to clinicians and necessitates inclusion of this neuroinflammatory syndrome in the differential diagnosis of neuro-oncological disease.

Breast carcinoma shows extensive clinical and molecular heterogenicity. Glycoprotein gp96 is considered a negative prognostic and predictive factor. Controversy exists over the prognostic role of tumor lymphocytic infiltrates. The goal of this study is to illustrate differences in gp96 and CD4+ and CD8+ T-lymphocytes expression among all immunohistochemical groups of breast carcinoma in relation to the clinical course and outcome of the disease. A retrospective observational study was conducted through processing and analysis of 152 female patient tissue samples previously classified by immunohistochemistry. After immunohistochemical processing, the samples were microscopically analyzed and positive cells were manually calculated in the entire biopsy sample for each patient. In the group of patients with triple negative carcinoma, a significantly higher number of CD4 positive cells in patients with no local recurrence were proven, as well as a significant correlation between a smaller number of CD4 positive cells with a lethal outcome. In the group of patients with Luminal B HER2+ carcinoma, a significantly higher proportion of CD8+ cells in patients with local recurrence were demonstrated. The highest glycoprotein gp96 expression was demonstrated in the group of patients with triple negative carcinoma, while the lowest in patients with Luminal A and Luminal B HER2- carcinoma. This study has shown significantly higher gp96 expression and higher extent of tumor lymphocytic infiltrate in more malignant types of breast carcinoma and represents a significant contribution in affirmation of the prognostic role of these variables.

Background Melanomas are rare in cats. The eye is the most commonly involved site, whereas few data are available about feline non-ocular melanomas (NOMs). Ki-67 thresholds with prognostic relevance have been established for canine melanomas, but not in cats. This study was undertaken to investigate the relationship between Ki-67 index, tumour characteristics, and clinical outcome in feline NOMs. Histologic samples were retrospectively reviewed. Amelanotic tumours were admitted upon immunohistochemical positivity for Melan A or S100. Evaluated parameters included morphological diagnosis, histotype, junctional activity, degree of pigmentation, vascular invasion, lymphocytic infiltrate, necrosis, mitotic count (MC) and Ki-67 index. Pigmented tumours were bleached before evaluation. Clinical and follow-up information were retrieved via telephone interviews with the referring veterinarians. Results Fifty tumours located in skin (n = 33) and mucosae (n = 17) were included. Forty-eight percent and 95% of amelanotic tumours (n = 21) stained positive for Melan A and S100, respectively. Most achromic tumours were mucosal (P 5, Ki-67 > 20% and lack of treatment administration. On multivariable analysis, only tumour histotype and treatment retained prognostic significance. Conclusions Although the majority of feline NOMs behave aggressively, Ki-67 index, together with other parameters, may contribute to prognostic assessment. Prospective studies on homogeneous populations are warranted to identify reliable threshold values for this marker.

Retiform hemangioendothelioma is a locally aggressive, rarely metastasizing, low-grade angiosarcoma characterized by intercommunicating vascular channels lined by hobnail or cuboidal endothelial cells, flanked by lymphocyte and hyaline sclerosis. Neoplastic endothelial cells usually express von Willebrand factor, CD31 and CD34, while the lymphocytic infiltrate shows a mixture of CD3+, T and CD20+ B cells. The authors describe a case of a 76-year-old female who presented with a soft, painless, ill-defined mass measuring 9 cm in her right gluteal region for the past 15 years, clinically suggestive of a lipoma. There was no regional lymphadenopathy. The mass was resected and sent for histopathological examination. The slow-growing lesion and the typical histomorphology led to the diagnosis of retiform hemangioendothelioma. The diagnosis was confirmed by immunohistochemistry using CD34 antibody, which strongly stained the endothelial cells. The patient was followed up for 6 months after the surgery and no recurrence was noted.

Introduction Idiopathic scrotal calcinosis is a benign and rare disease of the scrotal skin that presents as solitary or multiple asymptomatic calcified nodules in the absence of systemic disorders of calcium/phosphorus balance. Case reports We report the management of 2 cases and review the literature with comments on factors that determine acceptance or otherwise of surgical treatment. Our patients were 29 and 33 years old and presented with nodular scrotal lesions. Through multiple elliptical incisions, all nodules were excised from patient 1, but patient 2 refused surgery. Reasons for rejection included fear of future reproductive performances. Histology shows calcium deposition in basophilic globules of varying sizes and shapes within the reticular dermis, multinucleated giant cells, dense collagenous stroma, areas of fibrosis, and sparse lymphocytic infiltrate. Conclusion In the management of idiopathic scrotal calcinosis, factors that determine acceptance of surgical treatment could include impaired quality of life, reduced self-esteem, fear of future sexual dysfunction, and development of complications.