Dermatopathology, Volume 11, Issue 4 (December 2024) – 15 articles

The diagnostic utility of immunohistochemistry on paraffin-embedded sections in bullous disorders is useful when frozen tissue is not available. In pemphigus vulgaris and pemphigus foliaceus, an intercellular lace-like staining pattern of IgG4 on lesional tissue by immunohistochemistry has been described, with a comparable sensitivity and specificity to direct immunofluorescence on perilesional tissue. This study aimed to evaluate the staining pattern of IgG4 in non-immunobullous disorders to highlight the potential pitfalls when using this stain. In this study, we conducted a retrospective review of our institution’s database of non-immunobullous disorders where immunohistochemistry of IgG4 was performed to rule out pemphigus. We identified 27 cases where IgG4 immunohistochemistry was performed and observed intercellular IgG4 staining in some cases of Grover disease, bullous impetigo, irritated dermal hypersensitivity reaction, acantholytic actinic keratosis, and graft versus host disease. Our results indicate that the interpretation of IgG4 staining by immunohistochemistry in cutaneous acantholytic disorders should be approached with caution. Confirmation on cryosections with direct immunofluorescence study results is important in these settings. Full article

PRAME (PReferentially expressed Antigen in MElanoma) is a tumor-associated antigen first identified in tumor-reactive T-cell clones derived from a patient with metastatic melanoma. Immunohistochemistry (IHC) for PRAME is useful for diagnostic purposes to support a suspected diagnosis of melanoma. Anecdotally, PRAME has been observed to stain sebaceous units in glands in background skin. We examined the expression of PRAME in adnexal lesions and common skin cancers to determine whether it is of potential diagnostic utility in supporting the differentiation between sebaceous and non-sebaceous lesions. IRB approval from Mount Sinai Medical Center (MSMC) was obtained. This is a single-center retrospective cohort analysis over a ten-year period (1 January 2012, and 31 December 2023). We used the pathological database of skin lesions, including sebaceous, sweat gland, and follicular lesions, in addition to basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), from 81 patients who underwent shave/punch biopsies or surgical excisions. We evaluated the IHC staining percentage positivity and intensity for PRAME. Staining intensity was subcategorized into negative, weak, moderate, and strong, whereas expression percentage positivity was subcategorized into 0%, 1–25%, 26–50%, 51–75%, and 76–100%. Most sebaceous versus non-sebaceous lesions exhibited cytoplasmic staining of moderate to strong intensity in >75% of cells. PRAME has a sensitivity and specificity of 100.0% and 86.7%, respectively, to support distinguishing between sebaceous and non-sebaceous adnexal lesions (regardless of whether they are benign or malignant). BCCs and SCCs showed weak to moderate nuclear staining for PRAME in >75% of cells. None of the 13 lesions of hair follicle origin showed any staining. A total of 26 of the 32 lesions of sweat gland origin were negative while 6 (18.75%) showed positive staining. In conclusion, we confirm the potential utility of PRAME for supporting the distinction between sebaceous and non-sebaceous adnexal lesions on one hand, and on the other, distinguishing BCC and SCC that may show nuclear staining from sebaceous carcinoma that shows cytoplasmic staining. Full article

Malignant proliferating trichilemmal tumors (MPTTs), arising from the external root sheath of hair follicles, are exceptionally rare, with limited documentation of their genetic alterations. We present a case of a 64-year-old African American woman who initially presented with a gradually enlarging nodule on her posterior scalp. An initial biopsy at an outside hospital suggested metastatic adenocarcinoma or squamous cell carcinoma (SCC) of an uncertain origin. A subsequent wide local excision revealed a 2.0 cm tumor demonstrating characteristic trichilemmal keratinization, characterized by an abrupt transition from the nucleated epithelium to a laminated keratinized layer, confirming MPTT. Immunohistochemistry demonstrated diffuse p53 expression, patchy CD 34 expression, focal HER2 membranous expression, and patchy p16 staining (negative HPV ISH). A molecular analysis identified TP53 mutation and amplifications in the ERBB2 (HER2), BRD4, and TYMS. Additional gene mutations of uncertain significance included HSPH1, ATM, PDCD1 (PD-1), BARD1, MSH3, LRP1B, KMT2C (MLL3), GNA11, and RUNX1. Assessments for the homologous recombination deficiency, PD-L1 expression, gene rearrangement, altered splicing, and DNA mismatch repair gene expression were negative. The confirmation of ERBB2 (HER2) amplification in the MPTT through a molecular analysis suggests potential therapeutic avenues involving anti-HER2 monoclonal antibodies. The presence of the TP53 mutation, without the concurrent gene mutations typically observed in SCC, significantly aided in this differential diagnosis. Full article

Digital papillary adenocarcinoma (DPAC) is a rare, low-grade sweat gland carcinoma primarily found on the hands, fingers, or toes and predominantly affecting males. Distinguishing DPAC from benign sweat gland tumors can be challenging. We present the case of a 52-year-old patient with a progressive tumor on the finger initially misdiagnosed as a viral wart. Histological examination revealed a cytologically basophilic sweat gland tumor with tubular structures, papillary protrusions, and a characteristic immunohistochemical staining pattern for CK 7 and Actin. HPV-42 positivity and molecular analysis confirmed the diagnosis of DPAC. HPV-42 has been strongly associated with DPAC. Additionally, p16 positivity and BRAFV600E negativity were observed. These findings aid in the differential diagnosis of acral sweat gland tumors and guide clinical management, including with respect to the potential for recurrence and metastasis. Full article

Spindle cell lipoma (SCL) is a benign adipocytic tumor usually found in the subcutis of the posterior neck, upper back, and shoulder, predominantly in middle-aged males. This case report describes an atypical presentation of SCL in a 26-year-old male with a history of malignant melanoma. The patient presented with an erythematous plaque with central hyperpigmentation on the right upper arm, an uncommon location and presentation for SCL. Histopathological examination revealed an atypical myxoid spindle cell neoplasm with CD34 positivity and an overlying mildly atypical compound melanocytic nevus. The unusual clinical and histological features, combined with the patient’s melanoma history, complicated the differential diagnosis, which included dermatofibrosarcoma protuberans (DFSP) and solitary fibrous tumors (SFTs). A wide local excision with 2 cm margins was performed, and subsequent pathology confirmed clear margins, supporting the diagnosis of SCL. This case highlights the importance of including SCL in the differential diagnosis of CD34-positive spindle cell tumors, even when clinical and histological presentations are atypical, and underscores the need for thorough histopathological evaluation and a broad differential diagnosis in patients with a history of melanoma. Full article

The dermoscopic rainbow pattern (RP), also known as polychromatic pattern, is characterized by a multicolored appearance, resulting from the dispersion of polarized light as it penetrates various tissue components. Its separation into different wavelengths occurs according to the physics principles of scattering, absorption, and interference of light, creating the optical effect of RP. Even though the RP is regarded as a highly specific dermoscopic indicator of Kaposi’s sarcoma, in the medical literature, it has also been documented as an atypical dermoscopic finding of other non-Kaposi skin entities. We aim to present two distinct cases—a pigmented basal cell carcinoma (pBCC) and an aneurysmatic dermatofibroma—that exhibited RP in dermoscopy and to conduct a thorough review of skin conditions that display RP, revealing any predisposing factors that could increase the likelihood of its occurrence in certain lesions. We identified 33 case reports and large-scale studies with diverse entities characterized by the presence of RP, including skin cancers (Merkel cell carcinoma, BCC, melanoma, etc.), adnexal tumors, special types of nevi (blue, deep penetrating), vascular lesions (acroangiodermatitis, strawberry angioma, angiokeratoma, aneurismatic dermatofibromas, etc.), granulation tissue, hypertrophic scars and fibrous lesions, skin infections (sporotrichosis and cutaneous leishmaniasis), and inflammatory dermatoses (lichen simplex and stasis dermatitis). According to our results, the majority of the lesions exhibiting the RP were located on the extremities. Identified precipitating factors included the nodular shape, lesion composition and vascularization, skin pigmentation, and lesions’ depth and thickness. These parameters lead to increased scattering and interference of light, producing a spectrum of colors that resemble a rainbow. Full article

Akatsuki disease (also known as pomade crust) is characterized by skin lesions resulting from inadequate skin hygiene. It is sometimes influenced by underlying psychological factors. Akatsuki disease sometimes mimics cutaneous horn or skin cancer. However, there are no previous reports of skin cancer accompanied with Akatsuki disease. Herein, we report a 79-year-old woman who was referred to our department with a tumor on her left cheek. Before performing a biopsy, we recommended that her family assist with regular facial cleansing. Two months later, the scales and crusts on her entire face had disappeared and the tumor on the left cheek had reduced. Skin biopsy was performed, and histological examination revealed ulcerative basaloid lobules consisting of cells with a small cytoplasm and large hyperchromatic nuclei. Peripheral palisading and tumor-stroma clefting were observed. A diagnosis of basal cell carcinoma was made. Full article

Non-melanoma skin cancers (NMSCs), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), are highly prevalent and a significant cause of morbidity. Image-guided superficial radiation therapy (IGSRT) uses integrated high-resolution dermal ultrasound to improve lesion visualization, but it is unknown whether efficacy varies by histology. This large retrospective cohort study was conducted to determine the effect of tumor histology on freedom from recurrence in 20,069 biopsy-proven NMSC lesions treated with IGSRT, including 9928 BCCs (49.5%), 5294 SCCs (26.4%), 4648 SCCIS cases (23.2%), and 199 lesions with ≥2 NMSCs (1.0%). Freedom from recurrence at 2, 4, and 6 years was 99.60%, 99.45%, and 99.45% in BCC; 99.58%, 99.49%, and 99.49% in SCC; and 99.96%, 99.80%, and 99.80% in SCCIS. Freedom from recurrence at 2, 4, and 6 years following IGSRT did not differ significantly comparing BCC vs. non-BCC or SCC vs. non-SCC but were slightly lower among SCCIS vs. non-SCCIS (p = 0.002). There were no significant differences in freedom from recurrence when stratifying lesions by histologic subtype. This study demonstrates that there is no significant effect of histology on freedom from recurrence in IGSRT-treated NMSC except in SCCIS. These findings support IGSRT as a first-line therapeutic option for NMSC regardless of histology. Full article

Background: Tumor collision is a rare event, with an estimated incidence of 0.0017%. Seborrheic keratosis, melanocytic nevi, and basal cell carcinoma (BCC) are by far the most common entities involved in collisions. Most authors consider collision to be an incidental event. I planned a retrospective study comparing BCC/apocrine–sebaceous–follicular unit (ASFu) neoplasm collisions with squamous cell carcinoma (SCC)/ASFu neoplasm collisions. Materials and methods: Files from 2005 to 2017 from Dr. José Molina Orosa Hospital were assessed; in the review, cases of collisions between BCCs or SSCs and ASFu tumors, including cysts, were identified. Results: Out of 3247 BCC cases, 12 biopsies were retrieved. Of 825 biopsies, none belonged to the SCC group. The ASFu tumors that collided with a BCC were as follows: four hidrocystomas, three infundibular cysts, two steatocystomas, two trichilemmomas, one spiradenoma, and one clear-cell hidradenoma (one patient had two cysts associated with a BCC). These cases correspond to seven female patients and five male patients aged between 26 and 91 years old. A quarter of these patients were immunosuppressed. Most ASFu neoplasms were found to be located beneath the BCC (8/12). Discussion: To the best of my knowledge, this report describes three new collisions of BCCs with ASFu neoplasms (infundibular cysts, steatocystomas, and a spiradenoma). My results also suggest that immunosuppression could be a factor that predisposes a patient to these collisions. I review current hypotheses in an effort to explain these collisions and contribute some new theories. Full article

TRPS1 (Tricho-rhino-phalangeal syndrome 1) is a GATA transcriptional activator gene encoding for a protein used as a sensitive immunohistochemical marker of breast carcinomas. In dermatopathology, TRPS1 is used as a marker of mammary and extramammary Paget’s disease and is also expressed by a variety of primary cutaneous tumors, mostly of adnexal origin. So far, very limited data exist on the expression of TRPS1 in metastatic skin tumors. We studied the immunohistochemical expression of TRPS1 in 72 cutaneous metastatic tumors from the breast (n: 19) and other origins (n: 53) in order to assess its diagnostic usefulness. The intensity of TRPS1 immunostaining was expressed as a histoscore: the product of the percentage of positive cells (scored semi-quantitatively 0–4) and the staining intensity (scored 0–3). In normal skin, nuclear TRPS1 expression was predominantly observed in cells of adnexal structures (pilosebaceous follicles and sweat glands). Eighteen (18/19, 94.7%) metastatic breast carcinomas showed diffuse and strong TRPS1 positivity (histoscore 12). Lower reactivity was found in some other metastases, including from the lung (11/22), the female genital tract (3/4), and the kidney (2/4), whereas most (20/22) metastases from the digestive system and peritoneum, along with a case of metastatic prostate carcinoma, were negative. These results suggest that a high histoscore for TRPS1 is in favor of the mammary origin of metastatic cutaneous carcinoma. Although TRPS1 is not absolutely specific or sensitive to a particular primary, we consider that it can be added to a panel of other markers when investigating the origin of a cutaneous metastasis, namely when this is the first manifestation of the neoplastic disease. Full article

Undifferentiated pleomorphic sarcoma (UPS) is an aggressive soft tissue sarcoma with a poor prognosis. The patients are usually found to have metastasis when the primary tumor is diagnosed. Eccrine syringofibroadenoma (ESFA) is a rare cutaneous adnexal lesion of eccrine duct origin. There are five subtypes, one of which is reactive ESFA, known to occur in reaction to an inflammatory or neoplastic process. In this article, we report a case of the co-existence of both UPS and ESFA in a 70-year-old male patient, presenting with a painless, erythematous, irregular surface nodule with a peripherally extended brownish hyperkeratotic plaque on the right palm. The histologic findings revealed an ill-defined dermal tumor of atypical epithelioid and spindle-shaped cells with large pleomorphic hyperchromatic nuclei and abundant eosinophilic cytoplasm. Some of those cells were multinucleated giant cells in the stroma with vascular proliferation and mixed inflammatory cell infiltrate. The tumor cells, which were only positive for vimentin, supported the diagnosis of undifferentiated pleomorphic sarcoma (UPS). Meanwhile, the overlying epidermis demonstrated hyperkeratosis, papillated epidermal hyperplasia, and proliferation of anastomosing slender cords and strands of cuboid cells within loose fibrovascular stroma. These findings are the characteristics of eccrine syringofibroadenoma (ESFA). We describe here a patient in whom reactive ESFA occurred on and surrounded the UPS tumor. Full article

Considerable controversy exists within the field of dermatopathology in differentiating keratoacanthoma (KA) from squamous-cell carcinoma (SCC). KAs are rapidly growing, benign squamous tumors that are typically well differentiated. This controversy stems from the diverging perspectives on the management, classification, and diagnosis of each entity. Many believe that KAs are benign neoplasms in which intervention may be unnecessary since they are self-limiting and resolve on their own. On the other hand, SCC needs to be treated, as it carries significant morbidity and mortality risks. Early diagnosis and treatment are vital to prevent serious consequences of SCC. Nevertheless, KAs may resemble SCC grossly and microscopically. Various ancillary tests, including immunohistochemical (IHC) staining, have been proposed to differentiate between these entities, though mixed patterns of expression can limit the diagnostic utility of these techniques. Research into this topic is ongoing, with newer genetic and molecular findings illuminating the previously difficult-to-understand aspects of KA and increasing our understanding of this entity. In this review, KA and SCC will be compared along the lines of histological features, genetic, immune, and molecular markers, differential diagnosis, and management to clarify the similarities, differences, and misconceptions about both entities. Full article

A 11-year-old Caucasian girl presented to our Dermatology Unit with a 2-month history of an erythematous nodule, localized to the medial portion of her left eyebrow, rapidly growing in the two weeks before presentation. The histopathological examination revealed a dermal multi-nodular epithelial neoplasm composed of clear cells, squamous cells, and glandular cells, characterized by cytologic atypia, high mitotic activity, and an infiltrative deep growth pattern. The immunohistochemical profile of the lesion was as follows: CKAE1/AE3+, EMA+, CK8/18+, CK7+, CK19+, AR negative, p63 focally +, Ki67 25%, rare cells GCDFP15+, p53+. Full article

Dermatologic care within the military faces unique ethical challenges. Service members are stationed across nationally and globally diverse settings, and therefore, dermatologic care rendered ranges from within resource-rich, advanced military medical treatment facilities to austere, resource-limited, deployed field environments. Additionally, military service members are often at unique risk for dermatologic disease, given occupational, environmental, and geographic exposures not commonly faced by their civilian counterparts. This review explores topics in dermatoethics via case analyses of ethical considerations within the scope of dermatologic care for military service members. Full article