Clinicopathological Correlation Research Articles

Differential association of hedgehog pathway in development of cervical carcinoma and its chemo-tolerance

Cervical carcinoma (CACX) is still a dreadful threat to women in developing countries. Available conventional chemo-radiation therapies are not sufficient to restrict the disease recurrence. To unravel the mechanism of the disease recurrence, alteration of hedgehog self-renewal pathway was evaluated during development of CACX and in chemo-tolerance of the tumor. We have analyzed the alterations (expression/methylation/deletion) of some key regulatory genes (HHIP/SUFU/SHH/ SMO/GLI1) of hedgehog self-renewal pathway in cervical lesions at different clinical stages and compared with different datasets, followed by their clinico-pathological correlations. The changes in expression/methylation of the genes were then evaluated in two CACX cell lines (SiHa/HeLa) after treatment with chemotherapeutic drug cisplatin at different concentrations. Down regulation (mRNA/protein) of the antagonists HHIP and SUFU due to promoter methylation and/or deletion along with upregulation (protein) of agonists SHH, SMO and GLI1 was seen in early invasive lesions and subsequent clinical stages. Reduced protein expression of HHIP and SUFU showed significant association with high/intermediate expression of agonists SHH, SMO, GLI1 in the tumors and also poor prognosis of the patients. It was evident that cisplatin could restrict the growth of HeLa and SiHa cells through significant upregulation of antagonists HHIP and SUFU due to their promoter hypomethylation and down regulation of SHH in a concentration dependent manner without any significant changes in expression of SMO and GLI1, leading to the tumor cells in a dormant state. Thus, interplay of the agonists and antagonists has important role in activation of hedgehog pathway during development of CACX, whereas inactivation of the pathway due to upregulation of the antagonists is an important phenomenon in chemo-tolerance of the tumor. This suggests importance of epigenetic modification in chemo-resistance of CACX.

NCOA7 Regulates Growth and Metastasis of Clear Cell Renal Cell Carcinoma via MAPK/ERK Signaling Pathway.

NCOA7 is a nuclear receptor coactivator that is downregulated in a variety of cancers. However, the expression and prognostic significance of NCOA7 in clear cell renal cell carcinoma (ccRCC) remain unknown. The expression of NCOA7 in ccRCC tissues was analyzed using bioinformatics analysis, Western blotting, and immunohistochemistry. Kaplan-Meier analysis, the receiver operating characteristic (ROC) curve, and clinicopathological correlation analysis were used to assess the predictive power of NCOA7. Overexpression function tests were conducted in cells and mouse models to clarify the function and mechanism of NCOA7 in inhibiting the progression of ccRCC. NCOA7 expression was downregulated in all three subtypes of renal cell carcinoma, and only had significant prognostic value for patients with ccRCC. NCOA7 overexpression inhibited the proliferation, invasion, and metastasis of ccRCC cells in vivo and in vitro. Mechanistically, NCOA7 inhibited the MAPK/ERK pathway to regulate epithelial-mesenchymal transformation (EMT) and apoptosis, thereby inhibiting the progression of ccRCC. NCOA7 inhibits tumor growth and metastasis of ccRCC through the MAPK/ERK pathway, thus indicating its potential as a prognostic marker and therapeutic target for ccRCC.

Case of Generalized Granuloma Annulare Treated with Low Dose Naltrexone + PUVA

Granuloma annulare (GA) is a common, noninfectious granulomatous skin condition that usually presents in its localized form, characterized by flesh-colored to erythematous papules coalescing into annular plaques without scale, commonly on the dorsal hands. Lesions can be pruritic and often resolve without treatment in two years. However, the generalized form of GA has a lower incidence and presents with similar morphology, but with >10 lesions in a widespread distribution. Generalized GA is known to be more symptomatic, longer-lasting, and recalcitrant to treatment. The diagnosis is made based on clinicopathological correlation with palisading granulomas around degenerated collagen in the dermis, mucin, and infiltrative lymphocytes and histiocytes. Treatment remains challenging as evidence is limited to case reports, case series, and a few retrospective studies. Here we present the case of a 59-year-old Caucasian female with pruritic rash that began on her abdomen and spread to her extremities over two months. Biopsy revealed superficial histiocytic infiltrates palisading around eosinophilic areas of altered collagen, multiple multinucleate giant cells with elastophagocytosis and lymphohistiocytic perivascular infiltrates, and mucin in the dermis on colloidal iron staining. Overall, this was consistent with generalized GA. The patient was started on a combination of low dose naltrexone (LDN) and psoralen and ultraviolet A (PUVA) therapy. At a five-month follow up visit, she demonstrated near complete resolution of symptoms without any serious adverse effects.

Establishment of a novel signature to predict prognosis and immune characteristics of pancreatic cancer based on necroptosis-related long non-coding RNA.

Necroptosis plays an important role in tumorigenesis and tumour progression. Long noncoding RNAs (lncRNAs) have been proven to be regulatory factors of necroptosis in various tumours. However, the real role of necroptosis-related lncRNAs (NRLs) and their potential to predict the prognosis of pancreatic cancer (PC) remain largely unclear. The goal of this study was to identify NRLs and create a predictive risk signature in PC, explore its prognostic predictive performance, and further assess immunotherapy and chemotherapy responses. RNA sequencing data, tumour mutation burden (TMB) data, and clinical profiles of 178 PC patients were downloaded from The Cancer Genome Atlas (TCGA) database. NRLs were identified using Pearson correlation analysis. Then, patients were divided into the training set and the validation set at a 1:1 ratio. Subsequently, Cox and LASSO regression analyses were conducted to establish a prognostic NRL signature in the training set and validation set. The predictive efficacy of the 5-NRL signature was assessed by survival analysis, nomogram, Cox regression, clinicopathological feature correlation analysis, and receiver operating characteristic (ROC) curve analysis. Furthermore, correlations between the risk score (RS) and immune cell infiltration, immune checkpoint molecules, somatic gene mutations, and anticancer drug sensitivity were analysed. Finally, we used quantitative reverse transcription polymerase chain reaction (qRT-PCR) to validate the 5-NRLs. A 5-NRL signature was established to predict the prognosis of PC, including LINC00857, AL672291.1, PTPRN2-AS1, AC141930.2, and MEG9. The 5-NRL signature demonstrated a high degree of predictive power according to ROC and Kaplan‒Meier curves and was revealed to be an independent prognostic risk factor via stratified survival analysis. Nomogram and calibration curves indicated the clinical adaptability of the signature. Immune-related pathways were linked to the 5-NRL signature according to enrichment analysis. Additionally, immune cell infiltration, immune checkpoint molecules, somatic gene mutations and the half-maximal inhibitory concentration (IC50) of chemotherapeutic agents were significantly different between the two risk subgroups. These results suggested that our model can be used to evaluate the effectiveness of immunotherapy and chemotherapy, providing a potential new strategy for treating PC. The novel 5-NRL signature is helpful for assessing the prognosis of PC patients and improving therapy options, so it can be further applied clinically.

Elderly and Patients with Large Breast Volume Have an Increased Risk of Seroma Formation after Mastectomy-Results of the SerMa Pilot Study.

The collective of the SerMa pilot study included 100 cases of primary breast cancer or Carcinoma in situ who had undergone a mastectomy procedure with or without reconstruction of the breast using an implant or expander at Augsburg University Hospital between 12/2019 and 12/2022. The study aimed to investigate possible causes of seroma formation; reported here are the clinicopathological correlations between seroma formation and tumor biology and surgical procedures. Seroma occurred significantly more often in patients with older age (median patient age in cases with seroma was 73 years vs. 52 years without seroma; p < 0.001). In addition, patients with larger mastectomy specimen were significantly more likely to develop seroma (median ablation weight in cases with seroma 580 g vs. 330 g without seroma; p < 0.001). Other significant parameters for seroma formation were BMI (p = 0.005), grading (p = 0.015) and tumor size (p = 0.036). In addition, with insertion of implant or expander, a seroma occurred significantly less frequently (p < 0.001). In a binary logistic regression, age in particular was confirmed as a significant risk factor. In contrast, tumor biological characteristics, number of lymph nodes removed or affected showed no significant effect on seroma formation. The present study shows the need for patient education about the development of seroma in particular in older patients and patients with large breast volumes within the preoperative surgical clarification. These clinicopathological data support the previously published results hypothesizing that seroma formation is related to autoimmune/inflammatory processes and will be tested on a larger collective in the planned international multicenter SerMa study.

The lupus band test: A review of the sensitivity and specificity in the diagnosis of lupus erythematosus.

The lupus band test (LBT) is a direct immunofluorescence (DIF) technique which shows a band of localised immunoglobulins at the dermo-epidermal junction in lesional, non-sun-exposed skin of patients with both systemic and cutaneous lupus erythematosus (LE), and in perilesional skin of patients with systemic LE. However, low sensitivity and poor concordance between histological and clinical diagnoses warrant a review of the application of the LBT in the diagnosis of LE. To assess the sensitivity and specificity of the LBT in diagnosing LE following clinico-pathological correlation (CPC). All cases sent to our pathology department between 2011 and 2018 for DIF with a clinical query of LE were reviewed. Data collection included demographic details, pathology requests, histology and DIF reports, clinical reports and diagnoses, and serology. Of 256 histology requests, 9% (n=23) had a positive LBT. This was discordant with the prevalence of LE diagnosis, as 46.3% were diagnosed with LE following CPC. The sensitivity and specificity of the LBT for LE was 17.6% and 98.8% respectively, with a positive predictive value of 92.9% and negative predictive value of 58.2%. The LBT is not a sensitive diagnostic test for LE, but is highly specific, and should be considered as a supportive diagnostic tool for LE. This is the largest reported case series evaluating the efficacy of the LBT in the diagnosis of LE.

Differential diagnoses of benign eyelid tumors in children and adolescents

The clinical diagnosis as well as the treatment approach of periocular tumors in childhood and adolescence can be challenging. Knowledge of the most important differential diagnoses and their clinicopathological correlation is helpful for the treatment approach. The clinical and histological characteristics of various eyelid tumors in childhood and adolescence are presented taking the excision frequencies into consideration. The frequencies and clinicopathologic correlation of the most important eyelid tumors (n = 485) are presented based on the data of the ophthalmopathology laboratory of the University Eye Hospital Bonn from 1998-2023. The most frequent tumor in childhood and adolescence is chalazion (57.3%), followed by dermoid cysts (16.7%) and molluscum contagiosum (9.6%). Other lesions of childhood and adolescence include pilomatrixoma (2.1%), hemangioma and other vascular malformations (4.7%) and rare differential diagnoses, such as subcutaneous calcifying nodules and xanthogranuloma. Guidance on the approach in different age groups is presented in the form of adecision tree. Tumors in children and adolescents are mostly benign, yet there are important indications for excision. A histological examination of any excised tissue in childhood and adolescence is obligatory because unexpected findings are not uncommon and the spectrum of lesions also differs from that in adulthood. Knowledge of the histological picture can be very helpful in the preoperative clinical classification and for planning further procedures.

Assessment of Intratumoural and Stromal Infiltrating Lymphocytes In The Various Subtypes of Breast Carcinoma Patients who have Received Neoadjuvant Chemotherapy.

Breast cancer comprises a highly heterogeneous subset of tumours that respond well to Neoadjuvant Chemotherapy (NAC). Tumour Infiltrating Lymphocytes (TIL) act as a means to an end by shedding light on the treatment response as well as predictive factors to the clinicopathological features for the same. Therefore, this article attempts to shift the attention to the relevance of TIL in the aforementioned aspects by bringing to notice the contrasting traits displayed by them in the different immunohistochemical subtypes of breast carcinoma. 75 triple-negative breast cancer (TNBC) patients, 25 human epidermal growth factor receptor (HER2BC) positive patients and 77 hormone receptor (HRBC) positive breast cancer patients were included in this study who received NAC before surgical excision of the tumour which was then stained using routine Haematoxylin and Eosin techniques. Standardised guidelines were used to evaluate TIL in the stroma and the tumour. In TNBC, a significant association between Intratumoural (IT) TIL (p=0.0288) and Intrastromal (IS) TIL (p=0.0250) with pathological complete response (pCR). IS TIL and age at operation (p=0.0494) showed significant values but no correlation was found with IT TIL. In HER2BC, IS TIL revealed a significant association with the tumour response(p=0.0229). A strong association was found between IT TIL and the age of menopause(p=0.0441). In HRBC, no significant associations were found between IT and IS TIL scores and the clinicopathological features. The predictive factors of TIL and complete response post-neoadjuvant chemotherapy can be a strong indicative factor for immunohistochemical markers. It also helps throw light on further studies which can be carried out to determine the clinicopathological features and TIL correlation in the various subtypes of breast carcinoma.

DP09 The lupus band test: a review of the sensitivity and specificity in the diagnosis of lupus erythematosus

Abstract The lupus band test (LBT) is a direct immunofluorescence (DIF) technique which shows a band of localized immunoglobulins at the dermoepidermal junction in lesional, non-sun-exposed skin of patients with both systemic (SLE) and cutaneous lupus erythematosus and in the perilesional skin of patients with SLE. However, low sensitivity and poor concordance between histological and clinical diagnoses warrant a review of the application of the LBT in the diagnosis of lupus erythematosus (LE). The aim of this study was to assess the sensitivity and specificity of the LBT in diagnosing LE following clinicopathological correlation (CPC). All cases sent to our pathology department between 2011 and 2018 for DIF with a clinical query of LE were reviewed. Data collection included demographic details, pathology requests, histology and DIF reports, clinical reports and diagnoses and serology. Of 256 histology requests, 9.0% (n = 23) had a positive LBT. This was discordant with the prevalence of LE diagnosis, as 46.3% were diagnosed with LE following CPC. The sensitivity and specificity of the LBT for LE were 17.6% and 98.8%, respectively, with a positive predictive value of 92.9% and negative predictive value of 58.2%. The LBT is not a sensitive diagnostic test for LE, but is highly specific and should be considered as a supportive diagnostic tool for LE. This is the largest reported case series to evaluate the efficacy of the LBT in the diagnosis of LE.

DP22 Cutaneous lymphoid hyperplasia: clinicopathological correlation and a therapeutic option

Abstract Cutaneous reactive lymphoid hyperplasia, also known as cutaneous pseudolymphoma, is an uncommon entity in which there are skin lesions that histologically, and sometimes clinically, mimic cutaneous lymphoma but are not, both morphologically and immunohistochemically. Correlating clinical, pathological, immunohistochemical and, occasionally, molecular findings is essential for the diagnosis (Romero-Perez D, Blanes Martinez M, Encabo-Duran B. Pseudolinfomas cutaneous. Actas Dermosifiliogr 2016; 107:640–51). Although the majority of cases can be regarded as idiopathic, certain infections and inflammatory conditions can precipitate cutaneous reactive lymphoid hyperplasia, examples of which include Borrelia infection, insect bite reactions and folliculitis (Mitteldorf, C, Kempf, W. Cutaneous pseudolymphoma – a review on the spectrum and a proposal for a new classification. J Cutan Pathol 2020; 47:76–97). The first case was an 18-year-old woman who presented with deep dermal and subcutaneous nodules for the last 5 years that started on her limbs and were slightly itchy. The nodules were firm and deep, with minimal surface changes (hyperpigmentation and adherent scale) but did not ulcerate. She also had nodules involving her buccal mucosa, inner lips and soft tissue in the nasal bridge and a couple of deep nodules on the cheeks. Pathological examination showed a dense lymphocytic infiltrate with plasma cells admixed with other inflammatory cells involving the deep dermis with an extension to the dermal/subcutaneous junction. The pathological picture was in the spectrum of deep tumid lupus/lupus panniculitis overlap and cutaneous lymphoid hyperplasia. Immunohistochemical stains showed a mixture of inflammatory cells with CD3+ and CD20+ cells. Lip mucosal biopsy showed florid reactive lymphoid follicular hyperplasia. Her condition was resistant to multiple systemic treatments. Eventually, she underwent treatment with rituximab and had satisfactory results. The second patient is an elderly female who had multiple erythematous papules, plaques and nodules on her face. Pathological examination showed a dense dermal lymphocytic infiltrate with periadnexal predilection and reactive follicles that also were highlighted by CD20, with Bcl2 and CD3+ cells around germinal centres. She was diagnosed as having cutaneous reactive lymphoid hyperplasia. Topical calcineurin inhibitors were initiated, with a good response. In conclusion, this paper highlights the term cutaneous pseudolymphoma/cutaneous reactive lymphoid hyperplasia, presenting a few cases with clinicopathological correlation and exploring some uncommon treatment options.

BT02 Use of teledermatology in the 2-week wait pathway: 5 years of positive data

Abstract Our teledermatology service was started in 2018 to facilitate the dermatology department’s move offsite and allow for the continuation of inpatient care digitally without the need for increasing staff levels or cross-site working. Its implementation also allowed for efficient adaptation and use throughout the COVID-19 pandemic and recovery following this period. Alongside these aspects, teledermatology has become integral in the department’s rapid-access 2-week wait (2WW) capacity. The pathway involves patients attending the department and undergoing a nurse-led review with upload of the history alongside macroscopic and dermoscopic photographs to the platform for consultant review and management. The platform conforms to all aspects of the British Association of Dermatologists’ teledermatology guidelines and is hosted on the National Health Service’s Health and Social Care Network. Of almost 4000 2WW referrals assessed by digital teledermatology between 2018 and the present, no referrals have been rejected for poor quality, only 1% required urgent face-to-face review with a consultant, 32% were discharged, 53% were booked in for a minor surgical procedure of which half were suspected to be cancer or precancer and performed urgently, and 14% were booked for routine review due to risk factors such a multiple moles and need for a full skin check. Our consultants can assess 40 patients on the digital platform in a 4-h period, and the overall cost is approximately half of a face-to-face clinic, including admin. Of all 2WW referrals, general practitioner diagnosis has remained quite constant, with 30% of lesions thought to be malignant melanoma (MM), 36% squamous cell carcinoma (SCC) and 3% basal cell carcinoma (BCC); in the remaining 31%, no diagnosis was made. Of those referred for surgery by the dermatology consultants, the clinical diagnosis was BCC in 20%, SCC in 22% and MM or MM in situ in 6%; the remainder was thought to be precancerous, atypical naevi or other. We have continued to demonstrate through audit that the clinicopathological correlation in the digital teledermatology clinic is as good as face-to-face clinics for lesion diagnosis because of the quality of the history and images. Our most recent satisfaction survey in 2022 showed 96% patient satisfaction with the initial teledermatology assessment; of those booked for a procedure, 88% strongly agreed that all concerns were addressed prior to surgery. All patients would recommend the service to friends and family. With nearly 5 years of data and continuous evaluation, we have shown the effectiveness of a well-designed, connected digital system in supporting our service without duplication of effort by clinicians or prolongation of the patient’s journey.

BH12 Granulomatous alopecia areata

Abstract A 46-year-old woman with Fitzpatrick skin type V presented with sudden-onset accelerated diffuse hair loss. Her other relevant medical history included Graves disease. Trichoscopy showed black dots, broken hairs with exclamation mark-like hairs and yellow dots. She was provisionally diagnosed with diffuse alopecia areata (AA). Laboratory work-up, including complete blood count, liver/renal parameters, antinuclear antibody and complement screen did not reveal any abnormality. Thyroid function and adjusted calcium level were all within the normal range. She had slight iron, folate and vitamin D deficiencies, which were treated with the appropriate supplements. A biopsy was taken from the scalp, and histological examination showed a nonscarring process with miniaturization, significant telogen shift and peribulbar granulomatous inflammation. Subsequent syphilis serology was negative, and serum angiotensin-converting enzyme was within normal limits. No clinical features of sarcoidosis or syphilis were observed. After careful clinicopathological correlation, she was diagnosed with granulomatous AA. We planned to treat her with diphencyprone; however, her hair grew back spontaneously after 2 months. AA is a nonscarring hair loss that can commonly affect the scalp and beard, as well as any hair-bearing surface on the body. It is a T-cell-mediated disease with characteristic histological features, including peribulbar lymphocytic inflammation with or without eosinophils, follicular miniaturization and an increase in catagen/telogen hairs. Peribulbar granulomatous inflammation is a rare histopathological finding in AA. In the context of alopecia, other conditions associated with histopathological granulomatous findings include sarcoidosis, syphilis and various forms of inflammatory and cicatrizing alopecia. To our knowledge, only five other cases of granulomatous AA have been reported. Notably, we describe the first case from the UK and only the second case internationally to show spontaneous resolution, suggesting that the prognosis of granulomatous AA is not dissimilar to histologically typical AA. To summarize, we have described a clinically typical AA with atypical histopathological findings. Granulomatous inflammation should not preclude a diagnosis of AA. This demonstrates the importance of clinicopathological correlation as the histopathology of alopecia could potentially be misleading.

Molecular detection of mononucleotide biomarkers of microsatellite instability in sporadic colorectal carcinoma patients with clinicopathological correlation

Objectives: To identify the frequency and types of microsatellite instability among a group of sporadic CRC patients and to correlate the findings with clinicopathological characteristics.&#x0D; Methods: During an 8-month period, all patients with sporadic CRC who attended to two teaching hospitals in Baghdad, Iraq were recruited to this cross-sectional study regardless of age, sex, ethnicity, or tumor characteristics. Demographic, clinical, and histopathological features were recorded. DNA was extracted from FFPE-blocks of the resected tumors and normal tissues. PCR amplification of five microsatellite mononucleotide repeat loci (BAT25, BAT26, NR-21, NR-24, and MONO-27) and 2 pentanucleotide repeat control markers (Penta C and Penta D) was performed to determine the MSI status. Capillary electrophoresis and Genetic Analyzer 3500 (Applied Biosystem, Japan) were used to separate and examine the products. Data were analyzed by Genescan software (Promega, USA). Instability of two or more loci is considered MSI-H.&#x0D; Result: In this study, ages of the 45 recruited patients ranged between 20-80 years, with a mean±SD of 55±12.3 years; of them, 31(68.9%) were ≥50 years; 25 (55.6%) were males. Rectal bleeding was the most frequent presenting feature [22 (48.9%)] patients; 23 (51.1%) of CRCs were located at recto-sigmoid region, 29 (64.4%) were T3 tumors, 34(75.5%) were non-mucinous adenocarcinoma, 39(86.7%) were moderately differentiated, 17 (37.8%) patients had stage III tumors; and 25 (55.5%) had lymphovascular invasion. MSI-H was seen in 5/45 (11.1%) patients; 3(60%) of them were ≥50 years, 4(80%) were males, 3(60%) were smokers, 2 (40%) presented with intestinal obstruction and altered bowel habits each; 4(80%) had T3 tumors, 3(60%) had mucinous adenocarcinomas [p=0.004], 2(40%) had stage II tumor and stage III each.&#x0D; Conclusion: The frequency of MSI-H among the recruited patients with CRC was 5/45 (11.1%) and it was significantly associated with mucinous adenocarcinoma subtype. NR-24 and NR-21 were the most prevalent instable markers.

P95 A single-centre retrospective study of the association between subacute cutaneous lupus erythematosus and malignancy

Abstract Subacute cutaneous lupus erythematosus (SCLE) is a rare photosensitive dermatosis that has been classically categorized as idiopathic or drug-induced. A proliferation of case reports and small case series support the hypothesis that the presentation of new-onset idiopathic SCLE can be a facultative paraneoplastic phenomenon. There remains a lack of consensus regarding the investigations that this dermatosis should initiate, and in which patients. The aims were to investigate the proportion of patients with biopsy-consistent SCLE who had an underlying malignancy, and to analyse the demographic, clinical and laboratory characteristics associated with this. We conducted a histopathology database word search of skin biopsy reports from 1995 to 2021. We performed a retrospective chart review of electronic and paper records and analysed demographic, clinical and laboratory data of patients with possible SCLE. This study received full ethical approval from the relevant local research ethics committee. Of 64 patients initially identified, 35 had SCLE following clinicopathological correlation and had sufficient data available for inclusion. In this cohort, a total of 16 (46%) patients had a malignancy, either preceding or following SCLE diagnosis. In eight (23%) patients, malignancy was diagnosed within 1 year of SCLE onset. SCLE was considered drug induced in 14 (40%) of cases. Eleven (31%) cases were considered to be idiopathic; of these, five (45%) were subsequently diagnosed with malignancy. Malignancies subsequent to the diagnosis of idiopathic SCLE all occurred in women (aged 66–74 years). There were no significant differences in the autoantibody profiles between patients with malignancy and the overall SCLE cohort. Malignancies were detected, on average, 41 days (range 11–74) after the diagnosis of SCLE. Subtypes of cancer diagnosed post-SCLE were lung (n = 4, all current or ex-smokers) and colorectal (n = 1, a never smoker). In four of these cases, investigation for malignancy was specifically advised by dermatology. This is the first reported retrospective study to explore the under-recognized association between SCLE and malignancy. Clinicians should be aware of the potential paraneoplastic nature of SCLE, especially in the context of risk factors such as smoking history and an older age profile.

BI21 The development of diffuse extragenital lichen sclerosus in a patient on palbociclib and fulvestrant for metastatic breast cancer

Abstract A 59-year-old woman with skin phototype VI was commenced on palbociclib (cyclin-dependent kinase 4/6 inhibitor) and fulvestrant (oestrogen receptor antagonist) as chemotherapy agents for metastatic breast cancer. Two months later, she developed a new widespread rash. Past medical history included atopic dermatitis but no autoimmune conditions. Denosumab was her only other medication. On examination, she had hyperpigmented thickened plaques with purple hue and sclerotic plaques with cigarette wrinkling on her buttocks, arms, neck, abdomen and axillae. She also had widespread hypopigmentation. Biopsies showed hyperkeratosis and a lichenoid inflammatory reaction with pigmentary incontinence. Clinicopathological correlation supported the diagnosis of extragenital lichen sclerosus (EGLS). Palbociclib and fulvestrant were stopped and she noted improvement of her rash within 3 weeks. She was also managed with potent topical steroids, which eased her symptoms and further improved the appearance. Lichen sclerosus (LS) is a chronic inflammatory condition affecting the anogenital area. EGLS occurs in approximately 15–20% of those with LS, and only 6% of patients with EGLS do not have genital involvement at diagnosis. LS and EGLS are characterized by white papules, sclerosus and erosions with atrophic plaques. In the skin of colour, the presentation is varied, with hypo- or hyperpigmentation. Currently, the pathogenesis of EGLS is poorly understood, with studies suggesting an autoimmune aetiology, with possible genetic, infectious, hormonal, trauma and drug associations. In addition to specific autoantibodies, the absence of a suppressive function of regulatory T cells may contribute to the induction of autoimmunity. A recent association with immune checkpoint inhibitors (ICIs) further establishes this link. There are 12 case reports of ICIs and LS/EGLS, but cell cycle inhibitors associated with EGLS have not yet been reported (Silvestri M, Cristaudo A, Morrone A et al. Emerging skin toxicities in patients with breast cancer treated with new cyclin-dependent kinase 4/6 inhibitors: a systematic review. Drug Saf 2021; 44:725–32). Laboratory studies demonstrate increased T-cell activation with abemaciclib, a cell cycle inhibitor, which has been hypothesized to have other autoimmune drug associations (Truong K, Jones-Caballero M, Chou S et al. Lichen sclerosus and immune checkpoint inhibitors: a case and review of the literature. Australas J Dermatol 2023; 64:158–61). Other possible theories contributing to the development of EGLS include the Koebner effect of deep intramuscular injection of fulvestrant or subsequent low-oestrogen state. To the best of our knowledge, this is the first case of EGLS following these chemotherapy agents. This case hypothesizes the role of cell cycle inhibitors contributing to the aetiology in a mechanism similar to that of ICIs. It also demonstrates the difference in presentation of EGLS in skin of colour.

BI02 Disseminated toxoplasmosis presenting as panniculitis in an immunocompromised patient

Abstract Inflammatory dermatoses and inflammatory reaction patterns to underlying systemic disease are relatively uncommon in immunosuppressed organ transplant recipients (OTRs) and infection should always be suspected as a possible cause. We present an OTR with biopsy-proven panniculitis resulting from disseminated toxoplasmosis, only identified after extensive histological analysis. A 45-year-old Nigerian woman who was profoundly immunocompromised through a combination of a kidney transplant 12 months earlier, hyposplenism due to sickle cell anaemia and a CD4+ count 74 × 106 cells L–1 (&amp;gt; 455 × 106 L–1) presented with a 3-month history of &amp;gt; 20 painful, red–purple and hyperpigmented subcutaneous nodules and plaques up to 2 cm in diameter limited to her legs, associated with fatigue and weight loss. She only had childhood contact with cats. There was no lymphoedema or lymphadenopathy, and she was HIV negative. Urgent skin biopsy excluded Kaposi sarcoma and demonstrated a lobular, necrotizing panniculitis, a mixed inflammatory cell infiltrate and evidence of vasculitis. The cause was unclear; cultures for mycobacterial, fungal and bacterial infections were negative. However, on rereview of histology, within areas of inflammation and necrosis in the subcutaneous fat, there were a few scattered structures (10–30 μm in diameter) consisting of small basophilic periodic acid–Schiff-positive ‘dots’ within bright eosinophilic cytoplasm, raising the possibility of toxoplasmosis. Toxoplasma immuno­staining was positive. Further tertiary review of histology and immunostaining by the Hospital for Tropical Diseases agreed that there was no other causative organism and the panniculitis and vasculitis were consistent with active toxoplasmosis. The diagnosis of toxoplasma reactivation was supported by positive toxoplasma IgG on pretransplant bloods. Magnetic resonance imaging of the head was consistent with cerebral toxoplasmosis. She received treatment with clindamycin, pyrimethamine and folinic acid and, thereafter, long-term cotrimoxazole prophylaxis. Cutaneous toxoplasmosis is rare, with only three reported cases over the last 10 years. Historically, a wide spectrum of clinical morphologies has been described, including maculopapular rashes, nodules, ulcers, dermatomyositis and even mimicry of varicella and graft-versus-host disease. Most cases affect immunocompromised patients. In our patient, this was the result of reactivation of latent infection, which is more common in West Africa, coinciding with profound immunosuppression. In our case, a diagnosis was only made after extensive histological review. Given the varied morphologies of clinical presentations, it is possible that this condition may be easily missed, with potentially serious consequences. In summary, we highlight the importance of maintaining a high index of suspicion for infection and the need for careful clinicopathological correlation in OTRs presenting with apparently atypical inflammatory skin lesions.

Thoracic Aorta: Anatomy and Pathology

The aorta is the largest elastic artery in the human body and is classically divided into two anatomical segments, the thoracic and the abdominal aorta, separated by the diaphragm. The thoracic aorta includes the aortic root, the ascending aorta, the arch, and the descending aorta. The aorta’s elastic properties depend on its wall structure, composed of three distinct histologic layers: intima, media, and adventitia. The different aortic segments show different embryological and anatomical features, which account for their different physiological properties and impact the occurrence and natural history of congenital and acquired diseases that develop herein. Diseases of the thoracic aorta may present either as a chronic, often asymptomatic disorder or as acute life-threatening conditions, i.e., acute aortic syndromes, and are usually associated with states that increase wall stress and alter the structure of the aortic wall. This review aims to provide an update on the disease of the thoracic aorta, focusing on the morphological substrates and clinicopathological correlations. Information on anatomy and embryology will also be provided.

Hypertrophic Lichen Planus: An Up-to-Date Review and Differential Diagnosis.

Hypertrophic lichen planus (HLP) is a variant of lichen planus that can be difficult to diagnose based on histopathologic features alone. Thus, patient clinical history and clinicopathologic correlation are essential considerations to make the correct diagnosis. To discuss the clinical and histologic presentation of HLP and provide a thorough review of commonly encountered mimickers in the differential diagnosis. Data were derived from a literature review, personal clinical and research experiences, and a review of cases in the archives of a tertiary care referral center. In general, HLP involves the lower extremities and is characterized by thickened, scaly nodules and plaques that are often pruritic and chronic in nature. HLP affects both males and females and is most common in adults 50 to 75 years of age. Unlike conventional lichen planus, HLP tends to have eosinophils and classically displays a lymphocytic infiltrate most concentrated around the tips of rete ridges. The differential diagnosis for HLP is broad and encompasses numerous entities in many different categories, including premalignant and malignant neoplasms, reactive squamoproliferative tumors, benign epidermal neoplasms, connective tissue disease, autoimmune bullous disease, infection, and drug-related reactions. Therefore, a high index of suspicion must be maintained to avoid a misdiagnosis and potential inappropriate treatments.

Vesiculopustular eruption in a patient with chronic kidneydisease.

An 80-year-old man with stage 4 chronic renal disease, chronically medicated with amiodarone, presented with a vesiculopustular eruption on his face and neck two days after undergoing chest computed angiotomography with iodinated contrast. A skin biopsy showed dense neutrophilic infiltrate with cryptococcus-like structures. Clinicopathological correlation allowed the diagnosis of iododerma, which was later confirmed by raised serum iodine levels. Iododerma is a rare dermatosis triggered by the exposure to iodinated contrast and/or iodine-containing drugs. Although rare, dermatologists must recognize this polymorphic entity, mainly prevalent in patients with renal insufficiency.

Chromophobe-like carcinoma of the thymus: A clinicopathological and immunohistochemical correlation of 5 cases

Five cases of primary thymic carcinoma with distinct histopathological features resembling chromophobe carcinomas are presented. The patients were four men and one woman ranging in age between 43 and 72 years. Clinically, the patients presented with non-specific symptoms of dyspnea and chest pain. Diagnostic imaging revealed the presence of anterior mediastinal masses. All patients underwent complete surgical resection of their tumors via thoracotomy. Grossly, the tumors measured between 4.0 and 5.5 cm in greatest diameter and were ill-defined neoplasms with infiltrative borders; they were light brown in color and had a lobulated surface. Areas of hemorrhage and necrosis were not identified. Histologically, all tumors shared similar histopathological features, mainly the presence of infiltrative tumor islands separated by a fibrocollagenous stroma. At higher magnification, the neoplastic cellular proliferation was composed of medium-sized, round to polygonal cells with eosinophilic or granular cytoplasm and a clear perinuclear cytoplasmic halo, which imparted a chromophobe-like appearance. Nuclear atypia and mitotic activity were identified. Histochemical stains for colloidal iron were negative while immunohistochemical stains for pancytokeratin, cytokeratin 5/6, and p40 were positive in all cases, supporting squamous differentiation in these tumors. Clinical follow-up information was obtained in three patients all of whom died between 3 and 5 years after initial diagnosis, while two patients were lost to follow-up. The cellular characteristics of these tumors represent an unusual variant of thymic carcinoma that may pose a diagnostic challenge in small biopsies and that could be easily confused with other primary or metastatic tumors.