Dermatopathology

The use of levamisole as the most frequent adulterant of cocaine has merged in previously unknown toxicities, notably a disease entity called cocaine/levamisole-associated autoimmune syndrome (CLAAS). Clinically, CLAAS can manifest with diverse cutaneous and extracutaneous features sharing common laboratory findings (neutropenia, autoantibody patterns). We report the case of a cocaine-abusing female patient with relapsing episodes of painful ulcers, worsening and expanding over a three-year period. The case exhibited all features of a drug-induced, skin-limited, ANCA-associated vasculitis, evolving over time to PG-like findings. In both disease stages, the patient responded well to the cessation of cocaine exposure and systemic glucocorticosteroids. This case demonstrates the continuous nature of cutaneous CLAAS manifestations in a single patient. CLAAS has become a major public health issue in the at-risk group of cocaine users, and clinicians should be alert of this condition when treating cocaine users presenting with single or multiple skin ulcerations. Full article

Subungual exostosis (SE) is a well-recognised benign proliferation of the distal phalanx most often seen in young adults and affecting the big toe. Possible triggers include previous trauma and chronic irritation or infection. We describe two atypical cases of SE in two young women presenting with pyogenic granuloma-like lesions clinically. Diagnostic biopsies were performed to confirm the diagnosis and excluded amelanotic melanoma. However, histology unexpectedly revealed reactive myofibroblastic proliferations mimicking nodular fasciitis overlying the SE. Given the atypical clinical presentation, the diagnosis was initially missed or not considered in both patients. They highlight two important points; the first is that SEs may present with pyogenic granuloma-like lesions clinically and that histological analysis is then required to exclude malignancy, particularly amelanotic melanoma. Secondly, that the histology will show a reactive myofibroblastic proliferation and if the sample is relatively superficial and pathologists are not aware of this potential reaction pattern, the underlying diagnosis of SE may be missed. Full article

Background and Objectives: Basal carcinoma of the skin (BCC) is part of the nonmelanoma skin cancer (NMSC) family and is the most frequently occurring type of skin cancer in humans. A combination of clinical and histopathological approaches is necessary in order to establish the best treatment regime for patients who have been diagnosed with this type of cancer. The objective of the present study was to establish the statistical value of prediction for certain sociodemographic characteristics (age category and environment of origin) and histopathological parameters of the subjects that could be related to the incidence of diagnosis with certain histopathological subtypes of BCC. Materials and Methods: In order to verify the veracity of the established research hypotheses, we conducted a retrospective study based on the histopathological reports of 216 patients who were treated at the Pathology Department of Mureș Clinical County Hospital. Results: Cystic BCC is higher in patients who are older than 71 years of age, and the superficial multicentric and keratotic subtypes are more frequently diagnosed in urban areas. Patients who have been diagnosed with the superficial multicentric BCC subtype are not usually very old in contrast to the patients who tend to be diagnosed with the cystic BCC subtype. The nodular BCC subtype is positively associated with ulceration (p = 0.004); the superficial multicentric BCC subtype is positively associated with intra- and peritumoral inflammatory infiltrate (p = 0.022, p = 0.034) and negatively associated with ulceration (r = −0.218, p = 0.001). The infiltrative BCC subtype is positively associated with ulceration (p = 0.021), and the keratotic BCC subtype is positively associated with peritumoral inflammatory infiltrate (p = 0.02). Conclusions: Depending on each patient’s epidemiological and sociodemographic data, a pattern can be established regarding the appropriate clinical and treatment approaches for that patient, which can be supported based on the implications of the histopathological diagnostic. This can lead to an improvement in the patient’s quality of life and increased satisfaction with the provided medical services. Full article

Pemphigus is a chronic blistering disorder caused by autoantibodies that target desmosomal proteins in the epidermis. Acantholysis may be absent, and pemphigus may present only with spongiosis and vesiculation, thereby leading to a misdiagnosis of eczema. Herein, we conducted a retrospective, observational, single-center study to establish a pattern of spongiosis in cases of pemphigus confirmed by direct immunofluorescence. Immunopathologically diagnosed pemphigus specimens from 2001 to 2020 were retrieved, and specimens with spongiosis were analyzed for the following features: vesiculation, acantholysis, spongiosis, inflammatory cells in the epidermis, and inflammation in the dermis. Cases of spongiotic dermatitis were used as control. Out of 99 immunopathologically diagnosed pemphigus specimens, 41 samples with spongiosis were identified. About one quarter of the specimens did not have acantholysis. Spongiosis in the middle to lower thirds of the perilesional epidermis (p = 0.030), exocytosis with either neutrophils or eosinophils (p = 0.016), dermal infiltrates composed of lymphocytes, eosinophils, and neutrophils (p = 0.012), and absence of Langerhans cell microabscesses (p < 0.001) were more common in pemphigus than control. Spongiosis in pemphigus may mimic eczema in patients without acantholysis. The subtle histological findings in this study provide diagnostic clues and suggest that further immunofluorescence should be performed to confirm pemphigus diagnosis. Full article

Maculopapular exanthem is a commonly encountered presentation in routine clinical practice, and differentiation between its two most common etiologies, i.e., viral- and drug-induced, often poses a diagnostic dilemma. Clinical, hematological and biochemical investigations are seldom reliable in distinguishing between a drug reaction and a viral exanthem. Certain key histopathological features such as the presence of a moderate degree of spongiosis, extensive basal cell damage with multiple necrotic keratinocytes and dermal infiltrate rich in eosinophils or lymphocytes and histiocytes may favor a drug exanthem, while distinctive epidermal cytopathic changes and lymphocytic vasculitis point towards a viral etiology. Similarly, notable immunohistochemical markers such as IL-5, eotaxin and FAS ligand may support a diagnosis of a drug-induced maculopapular eruption. Histopathological and immunohistochemical evaluations may help in distinguishing between the two etiologies when faced with a clinical overlap, especially in patients on multiple essential drugs when drug withdrawal and rechallenge is not feasible. Full article

Scar endometriosis or incisional endometriosis is the presence of endometrial tissues with glands in the previous incision or scar. Its overall estimated incidence after post-cesarean and post-hysterectomy is 0.03–0.4% and 1.08–2%, respectively. The patient presents with non-specific symptoms such as cyclical abdominal pain at the site of a previous surgical incision and scar and an abdominal lump with a cyclical increment in size, which is tender. The diagnosis is made only after the surgical excision with confirmation by histopathological analysis. We present the case of a 31-year-old female complaining of cyclical abdominal pain and a lump on the right side of a Pfannenstiel incision for five months. She had undergone two Lower Segment Caesarean Sections (LSCSs); the last surgery was eight months prior. Surgical excision was planned with the corresponding clinical features and radiological data. After the surgical excision, the sample was sent for histopathological examination, and scar endometriosis was diagnosed. Full article

Background: Rhabdoid melanoma is a rare variant of malignant melanoma with characteristic cytomorphologic features. Due to the potential loss of conventional melanocytic markers, histopathologic diagnosis is often challenging. We hypothesize that immunostaining for PReferentially expressed Antigen in MElanoma (PRAME) might have the potential to uncover the melanocytic origin of these dedifferentiated tumors. Methods: Four cases of rhabdoid primary melanomas were assessed by immunohistochemistry for expression of PRAME and conventional melanocytic markers. Immunohistochemical expression patterns were analyzed in the rhabdoid primaries and, if available, associated metastases. Results: All four cases of rhabdoid primary melanomas showed a strong nuclear positivity for PRAME, while the expression of conventional melanocytic markers S100, MART-1, SOX-10 and HMB-45 was variable between the analyzed cases. Conclusions: In summary, we report four cases of rhabdoid primary melanoma with high to intermediate expression of PRAME despite the partial and variable loss of other melanocytic markers. Hence, PRAME might facilitate the recognition of this highly aggressive entity to avoid misdiagnosis due to histopathologic pitfalls. Full article

Primary cutaneous gamma-delta T-cell lymphoma (CGD-TCL) is a rare cutaneous lymphoma. Panniculitis-like T-cell lymphoma (SPTCL) has a better prognosis than CGD-TCL. SPTCL is sometimes associated with autoimmune disease. A 64-year-old Japanese female with a history of dermatomyositis presented with subcutaneous nodules on the upper extremities and exacerbated dermatomyositis. A skin biopsy showed lobular panniculitis, a vacuolar interface change, and a dermal mucin deposit. Fat cells rimmed by neoplastic cells, fat necrosis, and karyorrhexis were observed. The atypical lymphoid cells showed CD3+, CD4−, CD8+, granzyme B+, CD20−, and CD56−. Polymerase chain reaction analysis demonstrated a T-cell receptor rearrangement. The patient was initially diagnosed with SPTCL, so the dose of prednisone was raised from 7.5 to 50 mg daily (1 mg/kg). After one month, erythematous nodules regressed, and muscle symptoms improved. Subsequently, prednisone was tapered, and cyclosporin A was added. After one year, the patient remained symptom-free and continued taking 7.5 mg prednisone and 100 mg cyclosporin A daily. Afterward, we immunostained skin samples with antibodies against TCR-ß and δ and found positive TCR-δ and negative TCR-ß. Therefore, we corrected the diagnosis to CGD-TCL, although the clinical course and the presence of dermatomyositis were reminiscent of SPTCL. Full article

Over the past several decades, the study of Spitz neoplasms has flourished, with expanded conceptualization and refined terminology, providing a framework for the assessment and classification of Spitz nevi, atypical Spitz Tumors, and Spitz melanoma. Cancer genomics have generated concepts such as driver and passenger genes and clonal evolution, which can be applied to Spitz tumors. Herein, we provide a historical perspective, followed by a summary of current knowledge and clinical approaches for these challenging tumors. Full article

Lupus vulgaris is a one of the most common skin infections in the Indian subcontinent. Even today, it often creates a diagnostic dilemma for both clinicians and histopathologists. We describe a case of lupus vulgaris that showed lichenoid granulomatous inflammation in the dermis. This pattern is not uncommon, but is rarely described in the literature as newer modalities currently take precedence in diagnosis. Our aim is to make clinicians and dermatopathologists aware of this pattern of inflammation seen in this common infection. Full article

A 19-year-old female with a history of pre-B cell acute lymphocytic leukemia (ALL) presented with two aggressive cutaneous squamous cell carcinomas (C-SCC) in the right hand. The patient was diagnosed with pre-B cell ALL at four years of age. She underwent chemotherapy with initial remission. However, recurrence of the pre-B cell ALL required an unrelated allogeneic cord hematopoietic stem cell transplant (alloHSCT). Post-transplant, the patient developed Graft-Versus-Host Disease (GVHD), which was treated with immunosuppressant therapy for six years until resolution. Fourteen years following the transplant, the patient developed a morbilliform drug eruption secondary to clindamycin. She consequently received prednisone treatment. During the treatment period, the patient developed a new ulcerated and tender nodule on the dorsal aspect of her right hand. Further histopathological biopsy confirmed the diagnosis of C-SCC, which required excision. Ten months following the excision, the patient developed an additional C-SCC nodule on the same right hand, separated by 2.6 cm from the prior C-SCC. She was referred for a ray resection procedure. This case illustrates a patient with multiple risk factors that may have contributed to the continued development of C-SCC. Such risk factors include: a prolonged course of immunosuppressant medications and voriconazole treatment. Additional research is needed to investigate the etiologies and risks of C-SCC development in patients who require a transplant and long-duration immunosuppressive therapy. Full article

Background: Cutaneous adverse drug reaction (CADR) is common in both inpatient and outpatient clinical settings and has been associated with a large variety of medications. Drug reactions represent a significant burden to the healthcare system due to increased hospital stay durations and associated costs. Moreover, some of these reactions may be life-threatening. The most common clinical manifestation of a CADR is a maculopapular drug eruption (MDE). Due to its many clinical mimics and associations with a variety of histopathologic patterns, maculopapular drug eruption is difficult to definitively diagnose from both a clinical and histopathological perspective. Summary: We reviewed the clinical and histopathologic features of 327 cases of MDE from several studies in the literature and summarized characteristic histopathologic findings and their frequencies of occurrence. We found that the most common and suggestive histopathologic features of MDE were epidermal spongiosis, lymphocytic infiltrate, and occasional necrotic keratinocytes; interface change at the DEJ; superficial perivascular and interstitial lymphocytic infiltrate with or without eosinophils and neutrophils in the mid-to-deep dermis and mild papillary dermal edema; and dilation of superficial vessels. The presence of multiple histopathologic patterns within the same tissue specimen is also suggestive of MDE. This review and analysis suggest that a biopsy may improve the diagnostic accuracy by both establishing common and uncommon features associated with MDE and reviewing features that help to exclude other causes of maculopapular eruption. Key Message: Histopathologic criteria for the diagnosis of MDE, while not entirely specific, may aid in establishing a differential that includes a drug eruption. Thus, a biopsy can be a helpful diagnostic tool when MDE is suspected by demonstrating findings suggestive of MDE or by ruling out clinical mimics. However, biopsy results cannot be used in isolation as clinical-pathologic correlation is paramount in MDE. Full article

Background: balloon cell melanoma represents less than 1% of all histological forms of malignant melanoma and represents a diagnostic challenge for the dermatopathologist. Methods: in this paper we present our cases of BCM found in our daily practice from 1 January 2008 to 31 December 2021, and we conduct a review of the literature relating to this entity in the period from the first description, 1970, to early 2022. Results: four cases of melanoma balloon cell have been extrapolated from our electronic database, while in the review of the literature we have identified 115 cases of patients with primary and/or metastatic BCM. Conclusions: we believe that future studies with numerous case series are essential not only to increase the knowledge of the pathophysiology of this neoplasm but also to correctly evaluate the response of BCM patients to new oncological therapies. Full article

Eccrine angiomatous hamartoma (EAH) is a relatively rare benign skin disease characterized by the proliferation of eccrine sweat glands associated with capillary hemangioma and the proliferation of other skin elements such as adipose tissue, hair, and epidermis. The onset of the disease is usually at birth or in childhood and tends to occur in the extremities of females, but it occurred in an adult male in this case. The patient was a 72-year-old man with a 12 × 12 mm light brown, elastic, slightly firm skin nodule on the flexor aspect of his right forearm. A biopsy revealed enlargement of blood vessels, sweat glands, sweat ducts, and erector spongiosum with both lumen dilation and narrowing, leading to the diagnosis of EAH. The histopathological features of EAH include a marked proliferation of microvessels, epithelial-like changes in vascular endothelial cells (such as enlarged nuclei), and infiltration of inflammatory cells, mainly lymphocytes and plasma cells. In adult-onset cases, EAH can be clinically difficult to distinguish from epithelioid hemangioma (EH), which differs in the predominance of microvascular proliferation and the presence of eosinophils in the infiltrating inflammatory cells. It can also be distinguished from EAH by the negative results of S100 and anti-EMA in immunohistological staining. In the current cases, we were able to differentiate the two cases from characteristic findings on HE staining. Full article

Immunohistochemical quantification of inflammatory cells in skin biopsies is a valuable tool for diagnosing skin diseases and assessing treatment response. The quantification of individual cells in biopsies is time-consuming, tedious, and difficult. In this study, we presented and compared two methods for the quantification of CD8⁺ T cells in skin biopsies from patients with psoriasis using both commercial software (Adobe Photoshop) and open-source software (Qupath). In addition, we provided a detailed, step-by-step description of both methods. The methods are scalable by replacing the CD8 antibody with other antibodies to target different cells. Moreover, we investigated the correlation between quantifying CD8⁺ cells normalized to area or epidermal length and cell classifications, compared cell classifications in QuPath with threshold classifications in Photoshop, and analyzed the impact of data normalization to epidermal length or area on inflammatory cell densities in skin biopsies from patients with psoriasis. We found a satisfactory correlation between normalizing data to epidermal length and area for psoriasis skin. However, when non-lesional and lesional skin samples were compared, a significant underestimation of inflammatory cell density was found when data were normalized to area instead of epidermal length. Finally, Bland–Altman plots comparing Qupath and Photoshop to quantify inflammatory cell density demonstrated a good agreement between the two methods. Full article

Background: The most common autoimmune blistering disease, bullous pemphigoid (BP), shows an increased prevalence in psoriatic patients and oncologic patients undergoing immune-checkpoint blockade (ICB). Even though the same autoantigens (BP180/BP230) are detectable, it remains obscure whether clinical or histopathological differences exist between these different groups of BP patients. In this study, we strived to analyze this matter based on own data and previously published reports. Methods: We performed an institutional chart review from 2010–2020 to identify BP patients with psoriasis (n = 6) or underlying ICB (n = 4) and matched them with idiopathic cases of BP (n = 33). We compared clinical characteristics, subtypes, and dermatopathological determinants (e.g., tissue eosinophilia/neutrophilia, papillary edema, lymphocytic infiltration) among the groups. Results: ICB-associated BP affects men more often and might show mucosal involvement more frequently. We found no statistically significant dermatopathological differences among the groups. Conclusions: Clinicians should be aware of an increased risk of BP in patients with psoriasis and oncologic patients receiving ICB; atypical pruritic skin lesions should prompt a workup including a skin biopsy for histopathology and direct immunofluorescence in these patients. Larger studies might be necessary to detect slight dermatopathological variation. Full article

Polarization of tumor associated macrophages (TAMs) has been shown to have prognostic significance in different cancer types. This study evaluates the macrophage subtypes that predominates in GMF. Cases of GCTCL from 2007–2020 were identified (n = 6), clinical data was extracted from the electronic medical record, and all pathology slides were reviewed to confirm the diagnosis. Immunohistochemistry (IHC) studies were performed to characterize M1 and M2 macrophage polarization. CD68 (PGM1), pSTAT1, and CD163 were used as pan macrophage, M1, and M2 markers, respectively. The macrophages with positive staining at hot spot per high power field were counted and recorded for data analysis. The average age of patients was 60.5 years [range, 21–78], five patients (83%) were women and 1 (17%) was a man. Five patients were Caucasian (83%), and 1 was Black/African American (17%). Two patients had late stage GMF with M2 (CD163) predominance and the other three had early stage GMF with M1 (pSTAT1) predominance. Our study suggests that macrophage polarization present in GMF tends to be M1 in early stages and M2 in advanced stages. Additional studies are needed to further elucidate the microenvironment of macrophages present in GMF. Such findings may lead to prognostic and therapeutic advances in GMF. Full article

Background: Cutaneous mixed tumors (CMTs) include benign, atypical, and malignant chondroid syringomas. This spectrum of entities is known to be a part of myoepithelial neoplasms, which display considerable genetic heterogeneity. In a previous report, a malignant chondroid syringoma (MCS) demonstrated PHF1-TFE3 gene fusion and strong TFE3 immunohistochemical (IHC) staining. The authors suggested that the MCS is genetically related to tumors with TFE3 rearrangements such as renal cell carcinoma and might have genetic heterogeneity. In this study, we aim to investigate potential TFE3 gene fusions with TFE3 IHC stain in a spectrum of CMTs. Materials: Eleven benign chondroid syringoma (BCS), one atypical chondroid syringoma (ACS), and one malignant chondroid syringoma cases were identified, stained with TFE3 IHC stain, and interpreted based on preset criteria. Results: ACS and MCS cases did not show any staining. In 7 of 11 BCS cases, weak (1+) staining was observed in less than 20% of the tumor cells and were considered negative. Additionally, in one BCS case, weak (1+) and (2+) staining was shown in approximately 15% and less than 1% of the tumor cells, respectively. Based on our positivity criteria, this case was also interpreted as negative. Conclusions: Our study failed to reveal possible TFE3 gene fusion by IHC staining in benign, atypical, and malignant chondroid syringomas. Although the negative staining in MCS suggests a genetic heterogeneity in this entity, further studies with larger case groups are needed for a more definitive conclusion. Full article