Internal Malignancy Research Articles

Erythroderma in the elderly.

Erythroderma is the end-stage condition caused by various inflammatory diseases, presenting with widespread generalized coalesced erythema on the trunk and extremities. Erythroderma is not a disease itself, but rather is a symptom expressing erythrodermic condition, which is frequently associated with inguinal lymphadenopathy, chills, and mild fever. The clinical characteristics include sparing the folds of the trunk and extremities (deck-chair sign), and cobblestone-like disseminated grouping prurigo; however, the deck-chair sign is not specific to papulo-erythroderma (Ofuji disease). Erythroderma is induced by various causes, such as eczema, psoriasis, atopic dermatitis, drug eruption, lymphoma, lichen planus, pityriasis rubra pilaris, autoimmune bullous diseases, graft-versus-host disease, dermatomyositis, internal malignancy, and others. By contrast, it is not uncommon for even thorough investigations to often fail to identify any significant underlying or occult diseases. Such cases are often diagnosed as idiopathic erythroderma. In elderly cases, some regard erythroderma as late-onset atopic dermatitis, even if the patient does not have a history of childhood atopic dermatitis, while others consider it as a distinct condition with immune responses similar to atopic dermatitis. The etiology of erythroderma is suggested to be a Th2-dominant condition with IL-4/IL-13 playing a central role, suggesting that therapies targeting those Th2 molecules may result in sufficient effects. In this review, the characteristics of erythroderma in the elderly and new therapeutic approaches are discussed.

52289 Eruptive Disseminated Porokeratosis – A Herald of Internal Malignancy

52289 Eruptive Disseminated Porokeratosis – A Herald of Internal Malignancy

Human exposure to uranium through drinking water and its detrimental impact on the human body organs.

Human exposure to high concentrations of uranium is a major concern due to the risk of developing numerous internal organ malignancies over time. In addition to the numerous attributes of uranium in the nuclear power industry, the radiological characteristics and chemical toxicity of uranium present a substantial risk to human health. This study aims to evaluate potential negative health impacts associated with the ingestion of uranium through drinking water in the Noida and Greater Noida region within the Gautam Buddha districts of Uttar Pradesh (India), due to extreme industrial revolution in this geological location. The mean concentration of uranium in drinking water of the examined area was estimated to range from 0.23 to 78.21µgl-1. The hair compartment biokinetic model is used to estimate the retention and radiological doses of uranium in distinct organs and tissues. Studies on time-dependent factors revealed variations in uranium retention, with lower levels observed in the Gastrointestinal Tract (GIT) region and higher levels on cortical bone surfaces causes the skeletal deformities. The kidney, liver, and other soft tissues (OST) exhibited a non-saturation pattern in the retention of uranium via exposure of drinking water. The age-wise non-carcinogenic and carcinogenic doses were estimated for the health hazards studies. The outcome of this study will be useful for water resource management authorities to supply safe potable water to the local residents.

Cutaneous Signs of Internal Malignancy

Cutaneous Signs of Internal Malignancy

Mucocutaneous Manifestations among Patients with Malignancies at a Tertiary Care Center in Maharashtra: A Cross-Sectional Study

Abstract Background: Malignant disorders are a leading cause of mortality and morbidity. Cutaneous manifestations may be presenting features of internal malignancies, leading to diagnosis of occult tumors, while others may occur as adverse reactions to therapeutic modalities. Aims and Objectives: To classify cutaneous manifestations among patients with malignant disorders, document their clinical profile, and analyze them with respect to age, gender, type of malignancy, and treatment. Materials and Methods: One hundred twenty patients with proven malignancy presenting with mucocutaneous lesions were enrolled in the cross-sectional study. On the basis of history, clinical examination, investigations and skin biopsy, the lesions were classified as (1) Primary cutaneous malignancy, (2) Cutaneous metastasis, (3) Paraneoplastic syndromes, (4) Mucocutaneous manifestations not related to malignancies, (5) Adverse effects secondary to treatment modalities. Results: One hundred twenty patients comprised 70 females (58.3%) and 50 males (41.7%). They were categorized as primary cutaneous malignancy (20.2%), hematological malignancies (15%), solid organ malignancy (50.9%), and gastrointestinal malignancies (5%). HIV seropositivity was seen in two patients (1.6%). Maximum belonged to Category 5 (60, 50%), of which 52 (86.7%) were adverse effects of chemotherapy with single patient showing radiation dermatitis and one patient in Category 3 (0.8%). Eleven patients showed cutaneous metastasis (9.1%), predominantly carcinoma breast. Clinically, primary cutaneous malignancies often presented as ulceronodular growths with squamous cell carcinoma being the most common histopathological type (30%). Anagen effluvium was the most common (35%) manifestation overall and in solid organ malignancies followed by melanonychia (16, 13.33%), cutaneous xerosis (9, 7.5%), and mucocutaneous hyperpigmentation (23, 19.16%). Conclusions: Mucocutaneous manifestations need prompt attention to facilitate timely diagnosis and improved outcomes.

A rare occurrence of Hodgkin lymphoma in a Xeroderma pigmentosum patient: A case report and literature review

Xeroderma pigmentosum (XP) is a rare genetic disorder characterized by extreme sensitivity to ultraviolet (UV) radiation, resulting in an increased risk of skin cancer and other UV-induced malignancies. Reports of hematological malignancies occurring in patients with XP are found in the literature, but they seem to be quite rare. This report describes a 29-year-old male patient with XP who developed Hodgkin lymphoma. The potential increased risk of lymphoma in XP patients is highlighted in this paper; however, further studies are needed to better understand the underlying mechanisms of lymphomagenesis in XP patients and to develop optimal treatment strategies for hematological and other internal malignancies in this setting.

Paraneoplastic dermatoses in a patient with gastric adenocarcinoma: cutaneous clues to internal malignancy

Paraneoplastic dermatoses in a patient with gastric adenocarcinoma: cutaneous clues to internal malignancy

Utilizing PTEN immunohistochemistry as a screening test for Cowden syndrome.

Cowden syndrome (CS) is a multisystem disease with an elevated lifetime risk of internal malignancy. We aim to assess the role of PTEN immunostain as a screening test for CS in a variety of common CS-associated neoplasms, with a particular focus on cutaneous tumors. We retrospectively searched for patients meeting criteria for CS and/or demonstrating germline PTEN mutation from 2008 to 2022. We then performed PTEN immunostains on tumors of these patients as well as control cases. Our study included 30 patients with CS who had a total of 25 CS-associated malignancies (13 thyroid, 8 breast, and 4 endometrial carcinomas). Specifically, there were 11 patients with biopsy-confirmed CS-associated cutaneous neoplasms, including 1 patient with multiple trichilemmomas and 3 with multiple sclerotic fibromas. In total, 45 CS-associated tumors (6 trichilemmomas, 7 sclerotic fibromas, 5 thyroid carcinomas, 18 adenomatous thyroid nodules, 6 breast carcinomas, and 3 endometrial carcinomas) and 31 non-CS cases (9 trichilemmomas, 5 sclerotic fibromas, 8 adenomatous thyroid nodules, and 3 thyroid, 3 breast, and 3 endometrial carcinomas) were available for PTEN immunohistochemical staining. PTEN expression was lost in 43 (96%) of 45 CS-associated lesions and retained in 30 (97%) of 31 sporadic tumors. The overall sensitivity and specificity of PTEN loss of expression as a screening test for CS were 96% and 97%, respectively. PTEN immunohistochemistry on CS-associated tumors, especially trichilemmomas, can serve as a readily accessible and cost-effective screening test for CS.

A Mirror of Metastatic Destiny – A Case Series of Cutaneous Metastases

Abstract Cutaneous metastases (CM) account for 2% of all skin tumors, with an incidence of ~2%–10% in patients with internal malignancy. It has a broad morphological spectrum and histologically mimics the primary tumor. Its advent portends a poor prognosis. The clinical manifestations, diagnostic histopathology, and clinical course of five patients with CM were analyzed, of which 2 were female and 3 were male, ranging in age from 43 to 70 years. Illustrating the indolent behavior of this entity, four out of the five patients developed CM despite adequate treatment of the primary malignancies. The histology of the CM and primary malignancy were in agreement. Out of the five patients, four opted for palliative therapy and one patient succumbed to the illness during the course of treatment. CM usually signifies recurrence or progression of malignancy, rarely it may be the initial presentation of an underlying malignancy. It uniformly upstages the malignancy and gravely impacts survival. Regular follow-up and a high degree of suspicion of seemingly benign progressive skin lesions in patients with internal malignancies are crucial for the timely detection of CM. Early identification can lead to a better understanding of disease progression and potentially assist in optimizing treatment strategies, even though options may be limited at this advanced stage.

Unveiling the genetic landscape of hereditary melanoma: From susceptibility to surveillance

The multifactorial etiology underlying melanoma development involves an array of genetic, phenotypic, and environmental factors. Genetic predisposition for melanoma is further influenced by the complex interplay between high-, medium-, and low-penetrance genes, each contributing to varying degrees of susceptibility. Within this network, high-penetrance genes, including CDKN2A, CDK4, BAP1, and POT1, are linked to a pronounced risk for disease, whereas medium- and low-penetrance genes, such as MC1R, MITF, and others, contribute only moderately to melanoma risk. Notably, these genetic factors not only heighten the risk of melanoma but may also increase susceptibility towards internal malignancies, such as pancreatic cancer, renal cell cancer, or neural tumors. Genetic testing and counseling hold paramount importance in the clinical context of suspected hereditary melanoma, facilitating risk assessment, personalized surveillance strategies, and informed decision-making. As our understanding of the genomic landscape deepens, this review paper aims to comprehensively summarize the genetic underpinnings of hereditary melanoma, as well as current screening and management strategies for the disease.

Spectrum of Cutaneous Metastasis in Visceral and Haematolymphoid Malignancies: A Cross-sectional Study at a Tertiary Care Centre in Kolkata, West Bengal, India

Introduction: Cutaneous Metastasis (CM) is the spread of malignant cells from a primary site of malignancy to the skin. The incidence of CM ranges from 0.5% to 9% of all patients with cancer. CM may be the first sign of clinically silent visceral cancer or can even be a clue to tumour recurrence and heralds a poor prognosis requiring intense chemoradiotherapy. Aim: To study the spectrum of CM of internal malignancies, including haematolymphoid neoplasms. Materials and Methods: This cross-sectional study was conducted at Department of Pathology, Command Hospital Kolkata, West Bengal, India, over a period of two years from April 2020 to March 2022 and data was analysed over the next six months. A total of 16 patients who developed CM secondary to underlying solid organ or haematological malignancy were analysed. Categorical variables were summarised as percentages. Data in tables were presented as the frequency of variables (categories) or as absolute numbers. Results: The parameters studied included the primary site of malignancies, the frequency of various histological types at the primary site, and the common cutaneous metastatic regions. The mean patient age was 55.25 years (ranges 24- 72 years) with no gender predilection (M:F=1:1). The most common primary cancer site was the kidney and the oral cavity 4 each (25%), followed by breast, lung, and haematolymphoid malignancy, 2 each (12.5%), and 1 each of thyroid and gallbladder (6.25%). The most common site of CM was the head, abdomen, and epigastric wall 07/16 each (43.75%). The majority of the CM were identified as adenocarcinoma on histopathology. Conclusion: The CM occurs rarely and can be the initial presentation of an occult internal malignancy or may suggest recurrence if diagnosed later. Renal cell carcinomas and squamous cell carcinomas of the oral cavity are the tumours that have a high predisposition for CM, and hence these patients require close follow-up and surveillance.

Clinical and Histomorphological Features of Cutaneous Adnexal Neoplasms: A Series of Eighteen Cases

Cutaneous Adnexal Neoplasms (CAN) are rare skin tumours with varied morphology that are often misdiagnosed clinically. The definitive diagnosis of these tumours can only be made by Histopathology (HP) based on their appendage differentiation. Though rare in occurrence, diagnosing these tumours is of prime importance, as they can mimic primary cutaneous carcinomas, cutaneous metastasis of a primary tumour, or can serve as markers of internal malignancy. Excision is mostly curative in benign tumours, and wide local excision needs to be performed to prevent recurrences. The aim of the present case series study was to investigate the histopathological spectrum of different CANs based on their appendage differentiation in a hospital-based study. A retrospective analysis was conducted over a period of 4.5 years, and all CAN cases diagnosed on HP were classified according to their appendage differentiation. The concordance between histopathological diagnosis and clinical diagnosis was calculated. Additionally, the frequency distribution of CAN in relation to demographic data was analysed. In the present case series, 18 cutaneous adnexal tumours were reported, showing a female predominance. The majority of the tumours 12 (66.67%) cases were observed in the head and neck region and exhibited a predominance of sweat gland differentiation 12 (66.67%) cases. The most common CANs were eccrine spiradenoma and pilomatrixoma, with 3 (16.67%) cases each. Sebaceous carcinoma and a rare case of Malignant Proliferating Trichilemmal Tumour (MPTT) accounted for 2 (11.11%) cases, being the only malignant tumours reported. The present study demonstrated only concordance of 4 (22.22%) cases between clinical and HP diagnosis. Therefore, the present series emphasises the importance of appendage differentiation in HP, which plays a crucial role in the definitive diagnosis, treatment planning and prognosis in CAN.

TRPS1 expression in primary and secondary extramammary Paget diseases: An immunohistochemical analysis of 93 cases

Extramammary Paget disease (EMPD) predominantly manifests de novo as primary EMPD, with less than 30 % of cases associated with underlying internal malignancy (secondary EMPD). Differentiating primary from secondary EMPDs based solely on histopathology poses challenges, often necessitating supplementary screening, such as endoscopy or imaging studies, to definitively exclude underlying carcinomas like colonic adenocarcinoma. Recently, TRPS1 immunohistochemistry, initially identified as a sensitive and specific marker for carcinomas and mesenchymal tumors of mammary origin, has been proposed for EMPD. In this study, we conducted a systematic assessment of TRPS1 expression across 93 EMPD cases, comprising 82 primary EMPDs and 11 secondary EMPDs. Our aim was to assess the potential utility of TRPS1 as a marker to differentiate between primary and secondary EMPDs. Our findings revealed that 88 % (72/82) of primary EMPDs displayed TRPS1 expression, while secondary EMPDs consistently lacked TRPS1 expression (100 %; 11/11). Within the primary EMPD group, consistent TRPS1 immunoreactivity was observed in lesions originating outside the perianal region, such as the groin/inguinal area, axilla, and trunk. Interestingly, a majority (91 %; 10/11) of primary EMPDs originating in the perianal region exhibited an absence of TRPS1 expression. Upon excluding cases of perianal primary EMPDs, the sensitivity and specificity of TRPS1 for primary EMPDs reached 100 %. Our findings suggest that TRPS1 expression holds notable sensitivity and specificity for primary EMPDs, particularly when arising from non-perianal cutaneous sites. Hence, in suitable clinical contexts, TRPS1 immunohistochemistry may emerge as a promising and valuable tool for distinguishing primary and secondary EMPDs.

Cutaneous Metastasis as a Diagnostic Prelude in a 48-year-old Female

Abstract Cutaneous metastasis (CM) describes the spread of a distant primary tumor into the skin. The overall incidence of CM ranges from 5% to 10% with breast cancer having the highest rate in women. CM of breast carcinoma origin may manifest as erysipelas-like erythema on the chest, having distinct raised borders and edema due to lymphatic obstruction termed as carcinoma erysipeloides. In most cases, CM is recognized after the initial diagnosis of primary internal malignancy. However, in 0.6–1% of cases, CM served as the first presenting sign of malignancy. A 48-year-old female presented with multiple, erythematous patches, and plaques with clear-cut raised margins, some topped with violaceous pinpoint papules and nodules on the chest, abdomen, and back. No palpable breast mass was appreciated. There was noted nipple retraction and axillary lymphadenopathy. A 4-mm skin punch biopsy revealed nests of large pleomorphic cells on the papillary dermis admixed with mitotic figures and attempts of ductal formation. CK7 and CEA were positive. Results of ultrasonography and mammogram were highly suspicious of malignancy. Core needle biopsy of the breast mass revealed an invasive ductal carcinoma. In the context of an eczematous presentation on the chest area without palpable nodules or mass on breast examination, a diagnostic challenge is expected. Interestingly, our patient represents a small group of CM having cutaneous lesions as their primary manifestation. A high index of suspicion supplemented with proper clinicopathologic and radiologic correlation is crucial for the diagnosis of CM. A multidisciplinary referral is required for adequate management and overall survival rate.

A clinico-histopathological study of skin appendageal tumours in a tertiary health care centre in western Odisha– A case series

Skin appendageal tumours (SATs) are those neoplasms that arise from pilosebaceous, apocrine, or eccrine sweat glands. These are a diverse group of tumours with both benign and malignant counterparts. They can be single, multiple, or have a syndromic association with internal malignancies. Benign adnexal tumours are more common, while malignant adnexal tumours are rare, usually locally aggressive, and have the potential for nodal involvement and distant metastasis with a poor clinical outcome. Therefore, proper diagnosis of SATs is important for therapeutic and prognostic reasons.This study aims to determine the clinico-histopathological correlation in cases of SATs in our hospital. It is a case series conducted over a one-and-a-half year period from January 2021 to July 2022. All clinically suspected cases of SATs were examined, biopsied, and subjected to histopathological examination. Histopathologically confirmed cases of SATs were finally analysed. Among twenty-four thousand two hundred twenty-four new patients attending OPD, 30 suspected cases of ATs underwent histopathological examination. Histopathology was confirmatory in only 12 cases (40%). 10 cases were benign, and two were malignant. Out of 10 benign cases, hidradenoma was noted in 3 (25%), trichoepithelioma in 2 (16%), proliferating pilar tumour, apocrine hidrocystoma, steatocystoma multiplex, hidradenoma papilliferum, and pilomatrixoma were seen in one each. Females (75%) outnumbered males (25%) in our study population.: SATs are infrequent and are not frequently observed in the field of surgical pathology. Histopathology is the gold standard for diagnosis.

Paraneoplastic syndromes in dermatology - cutaneous manifestations of internal malignancy

Introduction: Cutaneous manifestations linked with internal malignancies can exhibit a wide range of appearances.The ideal paraneoplastic marker is one that exclusively appears with a tumor, vanishes upon tumor treatment, and can potentially reemerge with tumor recurrence or metastasis. They are divided into two main categories: acquired and genetic conditions. Among acquired paraneoplastic syndromes a few are strongly correlated with internal malignancies, others have less pronounced associations. 
 Aim of the study: To review the current literature on the topic of dermatological paraneoplastic syndromes.
 Materials and Methods: We reviewed the literature available in PubMed, using the key words: “paraneoplastic syndromes”, “paraneoplastic dermatoses”, “paraneoplastic syndromes in dermatology”. 
 Results: We presented the most common, selected skin paraneoplastic syndromes. We indicated the types of neoplasms associated with these dermatoses and described their clinical appearance along with potential mechanisms of development. 
 Summary: Timely recognition of paraneoplastic skin manifestations is crucial as they can provide an opportunity for diagnosing and treating the underlying neoplasm. That’s why dermatologists and clinicians should be familiar with this topic to perform an early diagnosis of the underlying malignancy.

Complete Remission of Cutaneous Metastasis from Invasive Breast Cancer with Abemaciclib plus Letrozole

AbstractSkin metastases from internal malignancies can be the first clinical finding of cancer recurrence. If presentation is delayed, they may ulcerate and develop secondary infection. Through this case, we will highlight a case of breast cancer recurrence with extensive cutaneous metastases that clinically completely responded to oral systemic therapy, thereby obviating the need for chemotherapy and leading to stark improvement in performance status and quality of life.

Immunohistochemistry, Molecular Biology, and Clinical Scoring for the Detection of Muir-Torre Syndrome in Cutaneous Sebaceous Tumors: Which Strategy?

Background: Sebaceous neoplasms (SNs) always raise the possibility of an association with Muir-Torre syndrome (MTS) and permit to screen internal malignancies, colorectal and endometrial carcinomas, before they become symptomatic. Immunohistochemistry (IHC), molecular biology, and clinical examination are different approaches for detection of MTS. We conducted a retrospective analysis of non-selected SNs in order to determine the optimal tools to implement for MTS screening. Methods: Deficient MMR phenotype (dMMR) was determined by either IHC using antibodies directed to four mismatch repair (MMR) antigens on tissue microarray or molecular biology using pentaplex PCR. The Mayo Clinic risk score of MTS was calculated from medical records. Sensibility and specificity of each test for the detection of MTS were determined. Results: We included 107 patients, 8 with multiple SNs, for a total of 123 SNs (43 sebaceous adenomas, 19 sebaceomas, and 61 sebaceous carcinomas (SC)). Loss of at least one MMR protein was observed in 70.7% of tumors, while 48% had a microsatellite instable phenotype. Concordance between both techniques was 92.9%, with a 0.85 Cohen’s kappa coefficient. Nineteen patients (20.2%) had a ≥2 points Mayo Clinic risk score, one having a pMMR SC. Among the 13 patients with confirmed MTS, 2 had a low Mayo Clinic risk score (1 point). IHC had the highest sensitivity for MTS screening (100%) with a specificity of 34.1%, while a >2-point Mayo Clinic risk score had a lower sensitivity (92%) but a higher specificity (89%). Conclusion: To detect MTS in SN patients, the first-line Mayo Clinic risk score followed by IHC appears to be the most accurate strategy with lower cost for society. This strategy should be adapted to the medico-economic resources of each country.

Leser-Trélat Sign as a Marker for Underlying Pancreatic Cancer.

Early diagnosis and rapid treatment of cancer is essential for good clinical outcomes for patients. In this case, an 85-year-old man presented with failure to thrive and was noted to have rapid-onset, multiple seborrheic keratoses (Leser-Trélat sign) on his chest and back. He was ultimately diagnosed with pancreatic cancer using computed tomography. Leser-Trélat sign is a rare cutaneous marker for underlying malignancy. Identification of this sign can help guide diagnostic imaging and lab work to identify an occult internal malignancy, resulting in more rapid diagnosis, earlier treatment, and potentially better clinical outcomes.

DP20 Necrobiotic santhogranuloma of the scalp with nonprogressive thrombocytopenia: a case report

Abstract We present the case of an 84-year-old woman referred with a 6-month history of a lesion on her occipital scalp. Examination revealed a creamy-white, nonscaly nodule measuring 15 × 15 mm with surface telangiectasia. Her past medical history included basal cell carcinoma, stage 3 kidney disease, cardiovascular disease and osteoporosis. A diagnosis of necrobiotic xanthogranuloma (NXG) was confirmed on incisional biopsy, and the patient went on to have full excision. Given the association with haematological malignancies, and following discussion with our local haematologist, investigations included full blood count, bone profile, immunoglobulins, serum and urinary protein electrophoresis and serum free light chains. This revealed a low platelet count of 108 × 109 cells L–1 (reference interval 150–450) but no other significant abnormalities. Our local haematologist considered a bone marrow biopsy, but after discussion with the patient, this was declined. Necrobiotic xanthogranuloma is a rare non-Langerhans histiocytosis. It classically presents as a yellow, red or purplish papule or nodule in the periorbital region, so this case had an unusual site. The mean age of onset is in the sixth decade of life, with an equal sex distribution. Pathogenesis is unknown. Necrobiotic xanthogranuloma is associated with haematological malignancies, particularly paraproteinaemia and lymphoproliferative disease. Differential diagnoses include xanthelasma, chronic lupus erythematosus, sarcoidosis and necrobiosis lipoidica. Where lesions become infiltrative and plaque-like, mycosis fungoides and psoriasis can also be considered. Given the relatively rare nature of NXG, there is no consensus for optimal treatment. In localized skin lesions such as in our patient, surgical excision is often undertaken. Other reported treatments are directed at the associated paraproteinaemia and include chlorambucil and small-dose corticosteroids, cyclophosphamide, melphalan, azathioprine, thalidomide, interferon-α and intravenous immunoglobulin. Classical features on histology include palisading xanthogranulomas with foci of necrobiosis in the mid-dermis and diffuse granulomatous panniculitis with foreign body-type reaction and Touton giant cells. Our histology slides showed a relatively atrophic epidermis with a dense dermal and subcutaneous infiltrate consisting of lymphocytes, foamy macrophages, plasma cells and Touton-type multinucleate giant cells with areas of necrobiosis. There were also reactive lymphoid follicles with germinal centres. Given the association with internal malignancy, it is important to diagnose these lesions correctly. To date, our patient has not developed any haematological malignancy, although is at increased risk in the future and has been counselled and monitored accordingly. It remains unclear whether the presence of thrombocytopenia alongside NXG is a coincidental finding or marker for future lymphoproliferative disease, as there are no other published case reports of such an association.