Round Bodies Detected by Treponema pallidum Immunohistochemical Stain in Two Cases of Cutaneous Syphilitic Gummata.

ABSTRACT: Tertiary syphilis may present a diagnostic challenge due to negative nontreponemal serologies in up to 30% of cases and frequent lack of identifiable spirochetes on histopathology or other direct detection tests. We report 2 cases of round bodies staining with Treponema pallidum immunohistochemistry by light microscopy in biopsies from cutaneous syphilitic gummata. In 1 case, the finding was validated 3 times by 2 independent laboratories; in the other case, T. pallidum was detected by polymerase chain reaction in the biopsy sample. Spirochete round bodies have previously been reported in the setting of electron microscopy and fluorography, but to the best of our knowledge, have not been reported by light microscopy in a routine skin biopsy. Although the clinical implications are unclear, this may represent a helpful new paradigm for the diagnosis of tertiary syphilis.

Eosinophils in Traditionally Noneosinophil-Rich Dermatoses.

ABSTRACT: The presence or absence of tissue eosinophilia has previously aided in the diagnosis of inflammatory skin conditions. However, recent studies have elucidated the presence of eosinophils in traditionally eosinophil-poor inflammatory skin diseases, such as dermatomyositis (DM), psoriasis, and lichen sclerosus (LS). This systematic review of the literature explores previous studies of tissue eosinophilia in skin biopsies of dermatoses that are believed to be classically poor in eosinophil. We identified 26 studies, the majority of which were retrospective reviews. The percent of specimens with increased eosinophils in psoriasis ranged from 18%-73%, pityriasis rubra pilaris (PRP) 22%-63%, LS 29%-53%, DM 15%-44%, morphea 8%-45%, hypertrophic lichen planus (LP) 0%-21%, and oral LP 0%-4%. These reports of tissue eosinophilia in reputed eosinophil-poor dermatologic conditions present a diagnostic pitfall and suggest that tissue eosinophilia itself should not be used to rule out a diagnosis of one of these conditions.

A case of eruptive lichen spinulosus after toxic epidermal necrolysis.

We report a case of a 13-year-old boy who presented with eruptive monomorphic white papules on the trunk and arms involving regions previously affected by toxic epidermal necrolysis (TEN). Biopsy revealed compact keratin involving the hair follicle and sparse mixed perivascular infiltrate, findings consistent with lichen spinulosus. Improvement was noted after treatment with ammonium lactate 12% lotion. While cutaneous dyschromia and xerosis are common after TEN, lichen spinulosus has not yet been described in the literature. It is important for providers to be aware of any potential cutaneous sequelae of TEN that can affect quality of life in order to best counsel their patients.

Enfortumab Vedotin-Associated Toxic Epidermal Necrolysis-like Toxic Erythema of Chemotherapy.

ABSTRACT: Enfortumab vedotin is an antibody-drug conjugate used for treatment of urothelial cancer. It has recently been associated with several reports of Stevens Johnson syndrome/toxic epidermal necrolysis (TEN). In this report, we describe the case of a 63-year-old man who developed widespread, near full-thickness desquamation, clinically mimicking TEN but with histologic features of toxic erythema of chemotherapy. This distinction is significant because it may have implications for prognosis and treatment. Further investigation is needed to ascertain the incidence of true TEN versus clinical imitators in patients with enfortumab vedotin-related cutaneous toxicity.

A Clinical Perspective on the Automated Analysis of Reflectance Confocal Microscopy in Dermatology.

BACKGROUND AND OBJECTIVES: Non-invasive optical imaging has the potential to provide a diagnosis without the need for biopsy. One such technology is reflectance confocal microscopy (RCM), which uses low power, near-infrared laser light to enable real-time in vivo visualization of superficial human skin from the epidermis down to the papillary dermis. Although RCM has great potential as a diagnostic tool, there is a need for the development of reliable image analysis programs, as acquired grayscale images can be difficult and time-consuming to visually assess. The purpose of this review is to provide a clinical perspective on the current state of artificial intelligence (AI) for the analysis and diagnostic utility of RCM imaging. STUDY DESIGN/MATERIALS AND METHODS: A systematic PubMed search was conducted with additional relevant literature obtained from reference lists. RESULTS: Algorithms used for skin stratification, classification of pigmented lesions, and the quantification of photoaging were reviewed. Image segmentation, statistical methods, and machine learning techniques are among the most common methods used to analyze RCM image stacks. The poor visual contrast within RCM images and difficulty navigating image stacks were mediated by machine learning algorithms, which allowed the identification of specific skin layers. CONCLUSIONS: AI analysis of RCM images has the potential to increase the clinical utility of this emerging technology. A number of different techniques have been utilized but further refinements are necessary to allow consistent accurate assessments for diagnosis. The automated detection of skin cancers requires more development, but future applications are truly boundless, and it is compelling to envision the role that AI will have in the practice of dermatology. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Erythema Migrans and Interface Changes: More Than a Fortuitous Association.

The histology of erythema (chronicum) migrans (ECM) is classically described as a nonspecific perivascular infiltrate with a variable number of plasma cells and eosinophils. However, deviations from this pattern were described, such as focal interface changes or spongiosis, potentially posing a clinicopathological challenge. In this study, cases submitted with a serologically confirmed, clinically unequivocal, or highly suspicious diagnosis of ECM/Lyme disease between January 01, 2016, and September 01, 2018, were retrieved from the electronic database system and reviewed to delineate the histopathologic features of ECM. The series consisted of 14 cases. A superficial perivascular lymphocytic infiltrate was noted in all biopsies, accompanied by a deep and/or interstitial inflammatory infiltrate in 9 cases (64%). The inflammation ranged from relatively sparse to dense and prominent. At least focal interface changes were noted in 12 biopsies (86%). Eosinophils and plasma cells were noted in 7 (50%) and 10 (71%) cases, respectively. From a histologic standpoint, ECM is a protean entity and may manifest with a variable density of perivascular and/or interstitial lymphocytic infiltrate admixed with eosinophils and/or plasma cells and accompanied by focal interface dermatitis. Within the appropriate clinical context, ECM should be considered in the differential diagnosis of focal interface and/or sparse perivascular dermatitis.

Differentiating regressed melanoma from regressed lichenoid keratosis.

BACKGROUND: Distinguishing regressed lichen planus-like keratosis (LPLK) from regressed melanoma can be difficult on histopathologic examination, potentially resulting in mismanagement of patients. OBJECTIVE: We aimed to identify histopathologic features by which regressed melanoma can be differentiated from regressed LPLK. METHODS: Twenty actively inflamed LPLK, 12 LPLK with regression and 15 melanomas with regression were compared and evaluated by hematoxylin and eosin staining as well as Melan-A, microphthalmia transcription factor (MiTF) and cytokeratin (AE1/AE3) immunostaining. RESULTS: (1) A total of 40% of regressed melanomas showed complete or near complete loss of melanocytes within the epidermis with Melan-A and MiTF immunostaining, while 8% of regressed LPLK exhibited this finding. (2) Necrotic keratinocytes were seen in the epidermis in 33% regressed melanomas as opposed to all of the regressed LPLK. (3) A dense infiltrate of melanophages in the papillary dermis was seen in 40% of regressed melanomas, a feature not seen in regressed LPLK. CONCLUSIONS: In summary, our findings suggest that a complete or near complete loss of melanocytes within the epidermis strongly favors a regressed melanoma over a regressed LPLK. In addition, necrotic epidermal keratinocytes and the presence of a dense band-like distribution of dermal melanophages can be helpful in differentiating these lesions.

Epidermotropic B-Cell Lymphoma: A Unique Subset of CXCR3-Positive Marginal Zone Lymphoma.

BACKGROUND: Epidermotropic B-cell lymphoma is a very rare entity that has primarily been reported in the literature as anecdotal case reports. The majority of the reported cases exhibit a diffuse skin rash affecting middle-aged to older adults with a male predominance. The exact mechanism of marginal zone B-cell localization to the epidermis is unclear. MATERIAL AND METHODS: To describe a very rare subset of cutaneous B-cell lymphoma and explore potential pathogenetic mechanisms for the epidermotropic tendency, the hospital database and literature review was conducted to isolate cases of epidermotropic B-cell lymphoma. Routine hematoxylin and eosin stain followed by selective phenotypic studies. RESULTS: Two of the cases were encountered in the hospital database, whereas 5 cases have been previously reported; material was requested on previously reported cases and was received on 3 of them. In one of the 2 cases encountered in our database, the patient presented with a progressive skin rash over 7 months resembling pityriasis rosea. Subsequent to a diagnosis of B-cell lymphoma, further staging revealed bone marrow involvement. The other patient, an elderly female, presented with isolated nodules. The biopsies of both cases showed areas of superficial band-like lymphocytic infiltration with large monocytoid appearance and an epidermotropic pattern of lymphocyte migration into the epidermis. Neoplastic cells were extensively positive for CD20, CD79a, and BCL-2 and negative for CD10 and BCL-6. Of interest, a similar pityriasis rosea-like presentation was encountered in the cases reported in the literature. All patients were elderly males with established bone marrow, peripheral blood, and spleen involvement several months to years after the initial cutaneous presentation in 3 of them. None of the patients to date have died of lymphoma. CXCR3 epidermotropic B cells were detected in both our cases and in 3 of the 3 previously published cases. CONCLUSIONS: Epidermotropic B-cell lymphoma represents a subset of marginal zone lymphoma characterized by a papulosquamous rash most frequently resembling pityriasis rosea, occurring almost exclusively in older males. We speculate that aberrant expression of CXCR3 in marginal zone lymphoma of the skin is associated with migration of lymphoma cells to the epidermis and could lead to an epidermotropic pattern given the known role of CXCR3 expression in neoplastic T cells in the localization of mycosis fungoides to the epidermis. There is a tendency toward bone marrow, spleen, and peripheral blood involvement.

Epidermotropic marginal zone lymphoma simulating mycosis fungoides(†).

Cutaneous lymphomas can usually be distinguished by architectural features, where most atypical lichenoid infiltrates implicate cutaneous T-cell lymphoma (CTCL). We report a case of an 80-year-old man who presented with asymptomatic golden brown patches and diffuse pink papules on his trunk, buttocks and hips. Biopsies revealed a lichenoid infiltrate and areas of epidermotropism. Although the overall architectural pattern was compatible with mycosis fungoides, the lymphocytes had a more monocytoid and plasmacytoid appearance, and there were interspersed mature plasma cells. Immunohistological studies revealed that the pleomorphic lymphocytes were predominantly B cells (CD20\+ and CD79a\+) with a subpopulation of smaller bland T cells (CD3\+). Moreover, the B-cell immunophenotype was compatible with marginal zone differentiation (bcl-2+, bcl-6-, CD10- and CD5-) and showed a lambda light chain restriction, confirming monoclonality. These findings were diagnostic for cutaneous marginal zone B-cell lymphoma (MZL) with epidermotropism an entity which has only been reported twice in the literature, once in the setting of primary cutaneous disease, and once as cutaneous involvement of systemic disease. This case illustrates a rare pattern of cutaneous MZL, and underscores the importance of immunophenotypic characterization of cutaneous lymphomas in order to prevent the misdiagnosis of a CTCL.

Dermatomyositis with Eosinophils.

Dermatomyositis is an idiopathic inflammatory myopathy that often presents with symmetric proximal skeletal muscle weakness and characteristic skin findings. Typical skin biopsy findings include vacuolar changes of the basal layer, increased dermal mucin, and a predominantly lymphocytic infiltrate. We report a case of dermatomyositis presenting as intensely pruritic papules and plaques, with initial histopathology being atypical of dermatomyositis due to the presence of eosinophils. The initial biopsy demonstrated a superficial dermatitis with eosinophils, initially thought to represent a drug eruption. A second biopsy of the same cutaneous manifestation was performed at a later time given high clinical suspicion for dermatomyositis and demonstrated a more classic vacuolar interface dermatitis with increased mucin and an absence of eosinophils. Notably, increased pruritus was specifically associated with the lesion that demonstrated tissue eosinophilia. The case illustrates the importance of considering tissue eosinophilia in the histologic presentation of dermatomyositis.

Sebaceous neoplasms with mismatch repair protein expressions and the frequency of co-existing visceral tumors.

BACKGROUND: Visceral malignancy has been associated with sebaceous neoplasms in patients with Muir-Torre syndrome. However, no large studies have been done to evaluate the frequency of visceral tumors in patients with sebaceous neoplasms and mismatch repair (MMR) protein expression of the sebaceous tumors. OBJECTIVE: We sought to determine the frequency of visceral tumors in patients with sebaceous neoplasms, MMR protein expression of the sebaceous tumors, and the related surveillance practices of physicians. METHODS: We identified 85 patients with sebaceous neoplasms. Relevant clinical information was obtained via chart review and database searches. MMR protein expression was examined by immunohistochemistry. RESULTS: Nineteen of the 85 patients had a total of 22 visceral malignancies, of which 41% were genitourinary in origin. Ten of the 17 patients (59%) with visceral malignancy had loss of MMR expression in their sebaceous neoplasms or somatic MMR mutation. Thirty patients had other findings such as colonic adenomas and polyps. Of the 23 patients who had a family history of visceral malignancy, 9 had a personal history of visceral malignancy. LIMITATIONS: Only one sebaceous tumor from each patient (except one) was tested for MMR, which might reduce the sensitivity. CONCLUSION: Our findings demonstrate an increased frequency of internal malignancy in patients with sebaceous neoplasms compared with the general population, and highlight the heterogeneous nature of the visceral tumors. A majority of the sebaceous tumors show loss of MMR expression. The study reminds us to strive toward a consistent and comprehensive approach to screening for internal malignancy when a patient is given a diagnosis of a sebaceous neoplasm.

Relapse of Plasmablastic Lymphoma With Cutaneous Involvement in an Immunocompetent Male.

Plasmablastic lymphoma (PBL) is a rare type of non-Hodgkin lymphoma frequently found in the context of immunosuppression and infection with human immunodeficiency virus (HIV) and/or Epstein-Barr virus (EBV). A 33-year-old immunocompetent male presented with recurrent episodes of epistaxis and a growing intranasal mass. Excisional biopsy of the mass revealed an immunohistochemical profile diagnostic of PBL. Upon completion of chemoradiation, he underwent a transnasal endoscopic mucosal flap tissue rearrangement to restore patency for both functional and surveillance purposes. There was no endoscopic evidence of residual or recurrent disease. However, 8 months later, he was found to have a relapse involving the skin. The nasal cavity is one of the most common sites affected by PBL. Involvement of the nasal cavity may present with symptoms of persistent epistaxis accompanied by an enlarging mass. A plasmablastic immunophenotype in combination with HIV or EBV positivity can aid diagnosis.

Cutaneous angiosarcoma of the knee: a case report and review of the literature.

Cutaneous angiosarcoma is a rare, malignant, vascular tumor that usually occurs in the scalp and face region of elderly white men. The tumor also can involve areas of prior irradiation; chronic lymphedema, otherwise known as Stewart-Treves syndrome; and preexisting vascular lesions. We report an unusual case of angiosarcoma occurring on the knee of a 70-year-old white woman with a strong family history of malignant melanoma in the absence of any known predisposing features.