Dermatopathology of Cutaneous Cystic Lesions: A Practical Review With Diagnostic Clues and Pitfalls Background: Cystic lesions are common in the daily practice of dermatologists and dermatopathologists, and in most cases, a straightforward diagnosis can be done. Yet, some variants and situations may cause diagnostic problems or carry prognostic and/or systemic implications. Objective: To review the histopathological features of the most frequent cystic lesions, either true cysts or pseudocysts, and provide some clues and pitfalls to bear in mind for troublesome situations such as solid–cystic tumors; uncommon variants; incidental findings; artifactual, reactive, or infectious cavities; cysts as a warning of systemic and hereditary diseases; and malignant cystic tumors, either primary or metastatic. Methods: The histopathological diagnostic criteria of most cystic lesions and their potential caveats will be discussed, offering some diagnostic clues. Results: Cystic lesions of the skin can primarily be classified into true cysts and pseudocysts. The most frequent pseudocysts are sinus pilonidalis and mucin-filled cavities. True cysts can be divided according to their epithelial origin or differentiation into epidermal/pilar cysts, cysts from glandular appendages, and from embryonic remnants. Diagnostic dilemmas and possible pitfalls in cystic lesions are reviewed, offering some keys to solve them. Conclusions: Knowledge of the histopathology of cystic lesions contributes to their correct diagnosis, improving the management of patients.

Intraoral Cutaneous Hamartomas—Clinicopathologic and Immunohistochemical Characteristics of 3 Cases Abstract: Intraoral cutaneous hamartomas (ICHs) are uncommon mucosal lesions characterized microscopically by a combination of cutaneous structures, including various stages of follicular and sebaceous elements. Due to their rarity, the clinicopathologic and immunohistochemical attributes of ICHs have not been thoroughly delineated. Three cases of ICH were identified from our records, and formalin-fixed paraffin-embedded sections were immunohistochemically stained with antibodies against androgen receptor, estrogen receptor, and progesterone receptor, p63, factor XIIIα, and CD34. All 3 ICHs involved the buccal mucosa with an M:F ratio = 2:1 and mean age = 42.3 years (age range: 27–61 years). ICHs presented as thickened, painless, white and yellow plaques or nodules of long duration, measuring 0.6–1.5 cm. No history of skin graft in the area of the lesions was reported. Histopathologically, the lesions showed aggregates of rudimentary folliculosebaceous structures. Although well-defined piloerector muscles were present in all cases of ICH, bona fide hair follicles and isolated hair shafts were identified only in 1 case. The overlying oral epithelium exhibited epidermis-like morphological features, while inflammation was generally absent. Immunohistochemically, strong and diffuse nuclear staining for androgen receptor and factor XIIIα was observed in the sebaceous glands, and estrogen receptor and p63 reactivity were confined exclusively to the peripheral basal cells, while progesterone receptor staining was negative in ICHs. CD34 diffusely decorated the lesional stroma. In conclusion, ICH is a rare lesion composed of cutaneous elements in an abnormal location. A predilection for the buccal mucosa is reported in the current study.

Amyloid-Associated Alopecia: A Reappraisal Including Its Pathophysiology Abstract: Primary systemic amyloidosis has a varied clinical presentation, making it one of the great masqueraders of other disease entities in clinical medicine. The association of amyloidosis with alopecia is uncommon with at least 22 cases reported in the literature mostly in the setting of systemic amyloidosis. Alopecia in these patients occurs either as the initial presentation of the systemic amyloidosis or it happens during the disease course. The occurrence of amyloid alopecia associated with light chain (LC) restricted plasmacytic infiltrates in the absence of systemic amyloidosis, however, it is not well known. We report 3 cases of LC-associated amyloidosis presenting with alopecia, whereby there was evidence of a systemic plasma cell dyscrasia in 2 of the patients, one of whom developed multiple myeloma. None of the patients had systemic amyloidosis. Skin presentation in the patient with multiple myeloma was characterized by a diffuse form of alopecia affecting the entire scalp, eyebrow, and axillary and pubic hair in contrast to the localized form of alopecia noted in the other 2 patients. The mechanism by which LC-associated amyloidosis eventuates in this pattern of nonscarring alopecia potentially reflects the affinity of this form of amyloid for dermatan sulfate. Dermatan sulfate is found at highest concentrations within the adventitial dermis of the superficial to mid isthmic portions of the anagen hair follicles likely interfering with the hair cycle and induces early hair follicle involution. The result is a pattern of alopecia that can clinically and to some extent pathologically resemble either androgenetic alopecia or alopecia areata.

Syringotropic Mycosis Fungoides: A Variant of Folliculotropic Mycosis Fungoides or a Distinct Entity? Abstract: Syringotropic mycosis fungoides (MF) is classified under folliculotropic MF. Although there is significant overlap between the 2, this study demonstrates that folliculotropism is frequently present in syringotropic MF, and when not present, the specimen did not include a follicle to examine. In addition, few of the pathology reports mentioned folliculotropism or syringotropism, although this is an important prognostic feature.

Expression of Connexin 43 (Cx43) in Benign Cutaneous Tumors With Follicular Differentiation Introduction: Benign cutaneous tumors with follicular differentiation are alleged to differentiate toward parts of the hair follicle. Connexin 43 (Cx43) is a gap junction protein, the tumoral role of which has been investigated in several types of tumors. Objective: To study the pattern of expression of Cx43 in benign cutaneous tumors with follicular differentiation and to compare it with that shown by their alleged anatomical counterparts of the hair follicle. Materials and Methods: Five cases each of trichofolliculoma, trichilemmoma, fibrofolliculoma/trichodiscoma, trichoblastoma, trichoepithelioma, pilomatrixoma, and proliferating trichilemmal tumor, 3 cases of pilar sheath acanthoma, and 1 case of tumor of the follicular infundibulum were examined. Anti-Cx43 antibody was used. Results: Cx43 was expressed by all follicular tumors studied. Comparisons between trichoblastoma and trichoepithelioma and their respective normal counterparts could not be made. In 3 tumors (trichofolliculoma, pilomatrixoma, and the spectrum fibrofolliculoma/trichodiscoma), there was a parallelism between their Cx43 expression pattern and that of their alleged anatomical counterparts. In pilar sheath acanthoma, trichilemmoma, and the tumor of the follicular infundibulum, we only found partial similarities in Cx43 expression. Only the proliferating trichilemmal tumor showed a discordant pattern of expression. Conclusions: Cx43 expression is preserved in benign cutaneous tumors with follicular differentiation and the patterns of Cx43 expression in benign cutaneous tumors with follicular differentiation parallel those of their alleged anatomical counterparts in 5 types (either totally or partially). This preservation might be related to the good behavior of the entities studied.

Global PD-L1 Signals and Tumor-Infiltrating Lymphocytes: Markers of Immunogenicity in Different Subsets of Merkel Cell Carcinoma and Potential Therapeutic Implications Abstract: We previously studied the genetic and immunohistochemical profiles of subsets of Merkel cell carcinoma (MCC) stratified by morphology and Merkel cell polyomavirus (MCPyV) status. Recent advances in the immunotherapy of this disease prompted us to examine markers of immunogenicity [PD-L1 expression and tumor-infiltrating lymphocytes (TILS) in these subsets]. The observed clinical responses to checkpoint inhibition of the PD-1/PD-L1 pathway have not correlated with PD-L1 expression by MCC cells, and recent evidence suggests that functions of this pathway within the immune tumor microenvironment may be relevant. We conducted a semiquantitative (high, moderate, and minimal) immunohistochemical evaluation of the global PD-L1 signal in 52 cases of MCC, segregated in 3 subsets [pure MCPyV-positive (n = 28), pure MCPyV-negative (n = 9), and combined MCPyV-negative (n = 15)]. TILS were categorized as brisk, nonbrisk, or absent. Intersubset comparisons revealed that high global PD-L1 signals were exclusively associated with pure MCPyV-positive MCCs contrasted with virus-negative cases (P = 0.0003). Moderate signals were seen across all 3 groups. Brisk TILS were significantly associated with MCPyV-positive MCCs compared with MCPyV-negative cases (P = 0.029). Neither parameter (PD-L1 or TILS) was significantly different between the MCPyV-negative groups. Of potential clinical relevance, MCPyV seems to convey greater immunogenicity to MCCs than the high mutational burden/greater neoantigen load of MCPyV-negative cases. Interesting too is the fact that subset-related profiles of these markers mirrored those noted at genetic and immunohistochemical levels, separating pure MCPyV-positive MCCs from the virus-negative subsets.

Leukemic Vasculitis: Case Report and Review of the Literature No abstract available

A Case of Cutaneous Arteritis Presenting as Infiltrated Erythema in Eosinophilic Granulomatosis With Polyangiitis: Features of the Unique Morphological Evolution of Arteritis as a Diagnostic Clue Abstract: Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg–Strauss syndrome) is a rare systemic vasculitis affecting small- and medium-sized vasculature, associated with asthma and eosinophilia. Different levels of vasculitis in cutaneous lesions have been observed, including dermal small vessel vasculitis and subcutaneous muscular vessel vasculitis. Although the EGPA-associated small vessel vasculitis described as leukocytoclastic vasculitis can be often found in the documented literature, the features of subcutaneous muscular vessel vasculitis in EGPA-associated cutaneous lesions have been rarely demonstrated clinically and histopathologically in English literature. Herein, we report a case of EGPA involving infiltrated erythema on the extremities, with different stages of cutaneous arteritis characterized by eosinophilic arteritis and granulomatous arteritis in the same affected artery. We present this as a unique diagnostic clue for EGPA.

Palisaded Neutrophilic Granulomatous Dermatitis Leading to Diagnosis of Hodgkin Lymphoma: Report of Rare Case and Literature Review of Paraneoplastic Granulomatous Dermatitides Abstract: Palisaded neutrophilic granulomatous dermatitis (PNGD) presents as skin-colored to erythematous papules symmetrically distributed on extensor extremities. Histologically, interstitial and/or palisaded granulomatous infiltrates are present with neutrophils and leukocytoclasis. Together with interstitial granulomatous dermatitis (IGD), PNGD is considered a reactive granulomatous dermatitis to a systemic trigger including connective tissue disease, infection, medication reaction, and less commonly malignancy. We present the second case of PNGD leading to diagnosis of Hodgkin lymphoma. A 47-year-old woman presented with a new asymptomatic eruption of erythematous, nonscaly papules and thin plaques with variable annular configuration, symmetrically distributed on extremities. Biopsies revealed mid-dermal focal degeneration of collagen and leukocytoclasis in association with a palisaded mixed inflammatory infiltrate of neutrophils, lymphocytes, and histiocytes, some forming small granulomas. She had associated fevers, night sweats, weight loss, arthralgias and malaise. Imaging revealed retroperitoneal adenopathy. Excisional lymph node biopsy led to diagnosis of Hodgkin lymphoma. Paraneoplastic PNGD is rare with only 9 reported cases. In all cases, PNGD presented concurrently or before presentation of clinical signs/symptoms of underlying neoplasm. We reviewed a total of 37 cases of paraneoplastic PNGD/IGD, summarizing clinical presentation, histology, associated neoplasm, and response of the skin lesions to treatment. The most commonly associated neoplasia is hematologic, with myelodysplastic syndrome (9 of the 37 cases or 24%) being the most frequent. Seven cases of solid tumor malignancies (prostate, esophageal, hypopharyngeal, breast, endometrial, and lung cancers) have been reported. Recognition of paraneoplastic PNGD/IGD may allow dermatopathologists, pathologists, and dermatologists to direct further workup that reveals underlying malignancy.

Mycosis Fungoides Associated With Lesions in the Spectrum of Primary Cutaneous CD30+ Lymphoproliferative Disorders: The Same Process or 3 Coexisting Lymphomas? Abstract: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, primary cutaneous CD30+ lymphoproliferative disorders (pc CD30+ LPD) being the second most prevalent. There is evidence that MF and pc CD30+ LPD may coexist and share T-cell clonality, suggesting a common origin. These findings were supported by a T-cell receptor clonality assessment by the polymerase chain reaction coupled with capillary electrophoresis, although results produced by this method may be ambiguous. We describe an otherwise healthy 46-year-old man who developed, over the course of 5 months, a tumor consisting of primary cutaneous anaplastic large cell lymphoma and, subsequently, several papules of lymphomatoid papulosis (LyP). Both lymphomas appeared on a single patch of MF, which had been present on the patient's right buttock for at least 2 years. T-cell receptor clonality of the 3 types of neoplastic lesions and apparently non-involved skin were assessed by a next-generation sequencing-based method. We found that MF, primary cutaneous anaplastic large cell lymphoma and LyP harbored the same top 2 clones. Non-involved skin harbored other T-cell clones. In this patient, these findings suggest that MF, LyP and pc CD30+ LPD were different clinicopathological manifestations arising from the neoplastic proliferation of the same T-cell clone.