The American Journal of Dermatopathology

PD-L1 Detection—Pearls and Pitfalls Associated With Current Methodologies Focusing on Entities Relevant to Dermatopathology Abstract: PD-L1 is a transmembrane glycoprotein with an extracellular as well as an intracellular cytoplasmic domain. Physiologically, it plays a pivotal role in regulating T-cell activation and tolerance. Many tumor cells have exploited this regulatory mechanism by overexpressing PD-L1 in an effort to escape immunologic surveillance. In this review, we parse the literature regarding the prognostic value of tumoral PD-L1 expression before discussing the various methodologies as well as the pearls and pitfalls associated with each for predicting response to anti–PD-1/PD-L1 therapies. Special attention is given to cutaneous entities in which PD-L1 expression has been documented with an emphasis on cutaneous malignancies that have seen the broadest applications of anti–PD-L1/PD-1 therapies. Currently, immunohistochemistry is the method that is most commonly used for detection of PD-L1. However, with the wide array of immunohistochemistry protocols and staining platforms available in the market, there seems to be different cutoffs not just for different entities but also for the same entity. This review is an attempt to address the need for standardization and validation of existing protocols for PD-L1 detection.

Role of Histopathology in the Diagnosis of Cutaneous Leishmaniasis: A Case–Control Study in Sri Lanka Abstract: Cutaneous leishmaniasis (CL) displays a spectrum of manifestations clinically and histologically. Then, it becomes a diagnostic challenge and must discern from the other clinical and histological mimics, especially when the Leishman-Donovan bodies are inattentive. In this study, we compared the distinguishing histomorphological characteristics of CL against the other skin diseases with similar clinical and histological features. Skin biopsies of 181 patients, which suspect CL clinically, are evaluated histologically. Pertaining to the first case–control comparison, which performed between skin lesions of CL with or without discernible organisms and the other granulomatous dermatitis, highlighted that the ill-formed coalescent granulomata (OR = 14.83) and diffuse dense dermal plasma cell infiltrate (OR = 74.25) are significantly associated with the skin lesions of CL. The second case–control analysis was between CL without discernible organisms and the other granulomatous dermatitis, and identified a significant association in the presence of ill-formed coalescent granulomata (OR = 16.94) and diffuse dense (>50/HPF) dermal plasma cell infiltrate (OR = 74.5) in the skin lesions of CL. Pertaining to epidermal changes, acanthosis (OR = 2.38), spongiosis (OR = 9.13), and the presence of ulceration (OR = 20.26) are among the major concerns in CL. In conclusion, in the presence of clinical suspicion, dermal granulomata in ill-formed coalescent morphology with high plasma cell density in a diffuse arrangement are positive factors for the diagnosis of CL, especially when the discernible Leishmania amastigotes are absent. Resource utilization such as polymerase chain reaction and other ancillary techniques during the diagnosis of CL can be minimized by using a range of histopathological features and special attention should be focused on this in the future.

Renal Cell Carcinoma Antigen Expression in Primary Cutaneous Endocrine Mucinous Carcinomas: A Case Series of 14 Patients and Review of the Literature Abstract: Endocrine mucin-producing sweat gland carcinoma (EMPSGC) and primary cutaneous mucinous carcinoma (PCMC) are both uncommon low-grade cutaneous adnexal tumors with predilection for the eyelids of elderly women. Their clinical appearance is nonspecific, typically presenting as a slowly growing poorly circumscribed papule, nodule, plaque, or swelling. Histological features of EMPSGC include a lobulated dermal neoplasm with bland cytology and an invasive mucinous component in up to half of the cases. PCMC exhibits tumor nests suspended in abundant pools of mucin with focal strands or nests of tumor cells infiltrating the dermis. Because of their rarity and banal cytological features, both entities pose a risk for misdiagnosis with other benign/malignant cutaneous adnexal neoplasms. Histomorphological features can suggest a diagnosis of EMPSGC or PCMC, but immunohistochemistry is necessary for confirmation. A review of the literature showed variable results of antigens present in EMPSGC, and many of the positive markers only show sparse or focal immunoreactivity of tumor cells. As a result, diffusely positive markers play a crucial role in identification of these tumors, particularly with initial superficial biopsies. We present 9 cases of EMPSGC and 5 cases of PCMC with strong and diffuse immunoreactivity to renal cell carcinoma antigen. This novel finding can be useful in the diagnosis of EMPSGC and PCMC in combination with other known positive markers to differentiate them from other cutaneous neoplasms. In addition, it provides further evidence that EMPSGC could be a precursor lesion to PCMC with both existing on a spectrum.

Polypoid Compound Melanocytic Proliferations: A Clinicopathological Study Abstract: Nevi can show a polypoid appearance both clinically and histologically. Anecdotally, polypoid compound melanocytic nevus may exhibit a spectrum of junctional architectural and cytologic atypia, at times creating a diagnostic challenge by mimicking the radial growth phase of melanoma. To investigate this issue, we prospectively reviewed 40 polypoid compound melanocytic proliferations without overt malignant features. The lesions frequently occurred in young female patients and were predominantly from the trunk and intertriginous areas. Commonly observed atypical features included asymmetry (30%), shouldering (47.5%), poor circumscription (37.5%), and deep extension of melanocytes along the adnexal structures (67.5%). Severe cytologic junctional atypia (22.5%), dermal mitoses (10%), and pagetoid spread of melanocytes (5%) were less commonly seen. All lesions showed a reassuring dermal component with negligible cytologic atypia and maturation with depth. Overall, 7 lesions could not be readily classified as benign nevus; 5 of these in which a benign diagnosis was strongly favored were classified as atypical polypoid compound melanocytic nevi, whereas 2 lesions with diffuse severe junctional cytologic atypia and dermal mitoses were classified as ambiguous melanocytic proliferations. Atypical/ambiguous lesions were significantly larger and predominantly located in the axilla and groin. On molecular studies, none of the lesions tested showed the molecular profile of melanoma. We confirmed that polypoid compound melanocytic nevus can exhibit a variable degree of junctional atypia, likely related to frequent episodes of trauma and regeneration resulting in melanocytic proliferation. Pathologists should be aware of this phenomenon to avoid overdiagnosis.

Selection Criteria of Program Directors for Dermatopathology Fellows Abstract: Dermatopathology represents a unique field at the intersection of dermatology and pathology. Although programs are approved by the ACGME, there is neither uniformity in application materials, timetables, and deadlines, nor a centralized application process. Despite the competitive nature of dermatopathology fellowships, no formal studies have thoroughly examined the selection criteria by program directors. Our study fills this gap in the literature and evaluates the impact of selection criteria for dermatopathology fellows. Applicants can now gain insight into the most important and meaningful aspects of their application.

Cytoimmunofluorescence Diagnosis in Surgically Induced Pemphigus Foliaceus Abstract: Pemphigus foliaceus is an autoimmune bullous disease with autoantibodies against desmoglein 1. Case reports of pemphigus after surgery have also been described, which may simulate an infection of the surgical wound, a contact dermatitis, or even a tumor recurrence. Cytoimmunofluorescence can help to establish a rapid diagnosis.

A Unique and Rare Case of Extramammary Paget Disease With Concomitant Herpes Simplex Abstract: We describe a rare and unique case of extramammary Paget disease in the genitals with concomitant histological features of herpes virus infection. This is a very rare and interesting association that has only been reported in 1 article in the literature so far.

Endometriosis of the Eyelid, an Extraordinary Extra-abdominal Location Highlighting the Spectrum of Disease Abstract: Cutaneous endometriosis is an uncommon dermatologic disorder predominantly seen in young women. Most commonly, it presents within a region of a previous surgical scar, often in relation to a gynecologic procedure on the abdomen or in close proximity to the umbilicus. The typical clinical presentation is that of papules or nodules with monthly cyclical pain and size variation. Histologically, the lesions are composed of endometrial stroma and glands. The pathophysiology is not well understood but is believed to be due to metastasis or seeding of endometrial cells. When this uncommon disorder occurs outside of the most typical clinical setting, it may cause some diagnostic difficulty. In this report, we present the first known case of cutaneous endometriosis on the eyelid.

Cutaneous B-Cell Lymphoblastic Lymphoma Abstract: B-cell lymphoblastic lymphoma (B-LBL) is a malignant neoplasm of immature B cells that accounts for only 10% of all cases of lymphoblastic lymphoma. Most commonly, B-LBL presents as bony lesions, but in rare cases, the disease manifests cutaneously. We present a case of simultaneous cutaneous and systemic presentation of B-LBL in an otherwise healthy 28-year-old man in which the lymphoblastic infiltrate stained positive for CD79a, Tdt, CD10, and CD20. A diagnosis of cutaneous B-LBL was made, and systemic work-up revealed widespread involvement of the skin, bone, and lymph nodes. Review of all currently described cases of cutaneous B-LBL with or without systemic involvement revealed that the most frequently positive tumor markers were CD79a (92.3%), Tdt (90.6%), and CD10 (83.3%). Systemic involvement of B-LBL was found in nearly half of all cases with cutaneous presentation.

Primary Cutaneous Anaplastic Lymphoma Kinase–Positive Large B-Cell Lymphoma Abstract: Large B-cell lymphomas include several subtypes. Recently, anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma has been delineated as a distinct entity involving mostly lymph nodes and rarely affecting extranodal sites. We describe the first case of a primary cutaneous ALK-positive large B-cell lymphoma in a 48-year-old man with a solitary nodule on the back, and describe the histologic and phenotypic features. Accurate staging confirmed the absence of other lesions, and so surgical excision and postoperative local radiation therapy were initiated and resulted in complete remission. Two years later, extracutaneous spread with involvement of axillary lymph nodes occurred. Complete remission was achieved again by multiagent chemotherapy. Our case demonstrates that a primary cutaneous form of ALK-positive large B-cell lymphoma exists. The immunophenotypic analysis of cutaneous large B-cell lymphomas affecting the skin primarily or secondarily should include the assessment of ALK expression.