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Τρίτη 23 Ιουλίου 2019

Dermatopathology

Histopathology of Cutaneous Aging
imageAbstract: Aging is (so far) an inexorable and irreversible path in all species and organisms. In human beings, aging involving the skin has a special meaning because our appearance has become crucial for our social life in the modern world. Knowledge of the morphologic changes that happen during the aging process is crucial for understanding its pathogenesis, which in turn is necessary to approach it and even revert it. Skin aging happens because of 2 main sets of changes. Many —although not all—are the cause of exposure to external agents (extrinsic aging), of which the most important is solar exposure (also known as photoaging). In addition, skin also degenerates by mechanisms linked to genetically programed information (intrinsic aging). In this article, the histopathologic changes evident in exposed and nonexposed skin are examined.

Comparison of the Inflammatory Infiltrates in Tumoral Melanosis, Regressing Nevi, and Regressing Melanoma
imageBackground: Tumoral melanosis (TM) is a histologic diagnosis characterized by abundant pigment-laden macrophages in the dermis. It is generally thought to represent a regressed melanoma, although it has also been reported after benign pigmented lesions as well. Determining the antecedent lesion in cases of TM is of clinical importance to accurately guide therapy and prognostication. Comparing the histopathologic and immunohistochemical (IHC) characteristics of TM, halo nevi (HN), and regressing melanoma (RM) may help predict the antecedent lesion in cases of TM. Methods: Cases of TM, HN, and RM were selected and assessed for histopathologic (preservation of junctional melanocytic component, depth and width, solar elastosis, fibrosis, and preservation of rete ridge architecture) and IHC (SOX-10, CD138, and PD-1) parameters. PD-L1 immunostaining was also evaluated in cases of HN and RM. Results: Severe solar elastosis, fibrosis, and marked rete ridge effacement were more frequent in RM than in HN. By contrast, numerous plasma cells, clusters of lymphocytes expressing PD-1, and >50% PD-L1 expression in melanocytes were more common in HN than in RM. However, the association of these variables did not reach statistical significance. Discussion: Although studies with higher statistical power are needed, this study serves as an initial investigation to characterize the histopathologic and IHC characteristics, which may help better understand TM and its precursor lesions.

Observational Study Examining the Diagnostic Practice of Ki67 Staining for Melanocytic Lesions
imageBackground: Dermatopathologists routinely use Ki67 immunostaining to assess atypical melanocytic lesions with a dermal component to determine whether an ambiguous tumor is melanoma. However, there is no universal standard of use for Ki67 in melanocytic neoplasms. We sought to observe the real-world use of Ki67 in the diagnosis of melanocytic lesions and establish a best practice recommendation. Methods: We searched dermatopathology reports from 2 academic practices for melanocytic lesions in which Ki67 staining was used for diagnosis. The proliferation rate was compared between cases diagnosed as benign (not requiring re-excision), moderate to severely dysplastic or atypical Spitz nevi (requiring re-excision), and malignant melanoma. The use of other melanocytic markers and consensus review was also recorded and compared between institutions. Results: Pathology reports for 106 cases were reviewed. A high Ki67 proliferation rate (n = 18) favored a diagnosis of melanoma or nevi requiring re-excision (15/18, 83.3%) versus a benign nevus (3/18, 16.67%). A high Ki67 rate was 71.4%–90.9% sensitive and 40%–56% specific for the diagnosis of nevus requiring re-excision or melanoma. Institutional practices differed in regard to reporting of Ki67 staining, the use of multiple markers in the workup of atypical melanocytic lesions (HMB45, Melan-A, Ki67 being most common), and consensus review. Conclusions: A negative or low Ki67 proliferation rate correlates well with rendering of a benign diagnosis. However, a low proliferation rate does not preclude the diagnosis of melanoma. Ki67 staining is most commonly used as an ancillary test to support a diagnosis after other factors have been considered, such as histopathologic morphology and results of additional concurrently used stains.

Adipose Infiltration of the Dermis, Involving the Arrector Pili Muscle, and Dermal Displacement of Eccrine Sweat Coils: New Histologic Observations in Frontal Fibrosing Alopecia
imageBackground: Frontal fibrosing alopecia (FFA) is an irreversible scarring alopecia, and its incidence has reached epidemic size. Immune privilege collapse of the bulge and epithelial mesenchymal transition play a role in the pathogenesis. We have noted adipose tissue in the dermis in several specimens from FFA. Objective: Our primary objective was to verify the presence of adipose tissue at the isthmus level in biopsies from FFA. Additional objectives included the presence of deep inflammation and position of the sweat coils. Methods: Eighty-three histologic specimens of FFA diagnosed at the Dermatopathology Laboratory at the Department of Dermatology, University of Miami, within 3 years were evaluated retrospectively. All biopsies were bisected horizontally and assessed at several levels. Sixty biopsies from androgenetic alopecia served as controls. Statistical analysis was performed using the χ2 test. A P value of 0.05 or less was considered significant. Results: Sixty specimens met the inclusion criteria for optimal quality and classic diagnostic features. Seventy percent demonstrated fat tissue infiltration at the isthmus level as clusters of cells or small globules versus 23% of the controls. The fat infiltration in the arrector pili muscle (APM) was present in 55% versus 15% of the controls, and the sweat coils were positioned in the reticular dermis in 43% versus 1.7% of the controls. All results were statistically significant (P < 0.0001). When accounting for the simultaneous presence of any of these 3 variables, 30% of the FFA cases had triple positivity, 61.7% had double positivity, and 75% had at least 1 positive variable versus 0%, 15%, and 10%, respectively, of the controls. Conclusion: New histologic findings in FFA involve the presence of adipose tissue in the dermis. We believe that the close interaction of the hair follicles and the APM with the adipose tissue may play a role in APM degeneration and in epithelial mesenchymal transition.

Linear IgA Bullous Dermatosis Preceding the Diagnosis of Primary Sclerosing Cholangitis and Ulcerative Colitis: A Case Report
imageAbstract: Linear IgA bullous dermatosis (LABD) is a rare autoimmune blistering disorder seen in the pediatric and adult populations that is often linked to a medication, infection, or underlying gastrointestinal, hepatobiliary, or autoimmune disease. In this study, we describe the case of a 23-year-old white man whose presentation and diagnosis of LABD ultimately led to the discovery of underlying primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). His dermatitis resolved with topical steroids and dapsone, and he is undergoing systemic treatment for his UC and PSC. This exceptional case further validates the association between LABD with UC, strengthens that with PSC, and underscores the importance of alerting clinicians to consider conducting a systemic workup in addition to thorough medication history on making the diagnosis of LABD.

Dedifferentiated Melanoma With Expression of Cytokeratin and GATA3 in a Patient With History of Breast Carcinoma
imageAbstract: Melanoma is one of the great mimickers in pathology because it has diverse morphologies and can be mistaken for carcinoma or sarcoma. In most cases, immunochemistry is helpful in supporting the diagnosis and excluding other differentials. However, metastatic melanoma may lose immunohistochemical melanocytic markers and express nonmelanocytic lineage markers, which often poses a diagnostic dilemma and may be misdiagnosed as a poorly differentiated carcinoma or sarcoma. We report the case of a 52-year-old woman who had a history of recurrent melanoma on her right shoulder with axillary lymph node metastasis (BRAF V600K–mutated melanoma) and right-side breast-invasive ductal carcinoma (stage pT1b N0sn). One year later, she presented with a left-sided chest wall mass and enlarging left axillary lymph nodes. Needle core biopsies were obtained from both lesions, and histologic examination showed a poorly differentiated tumor with pleomorphic/anaplastic morphology and necrosis. The tumor cells were strongly immunoreactive for GATA-3 without expression of melanocytic markers (S100, Melan A, HMB45, SOX10, MITF, and tyrosinase). The history of melanoma prompted molecular analysis, and the lesion was found to harbor the BRAF V600K mutation, consistent with metastatic dedifferentiated melanoma. Recognition of metastatic dedifferentiated melanoma is important to avoid misdiagnosis of carcinoma, especially in patients with a previous history of carcinoma.

Localized Lichen Myxedematosus With Plasma Cell Light Chain Restriction: Is It the Exception or the Rule?
imageLichen myxedematosus is a chronic cutaneous mucinosis that can present on a spectrum from localized cutaneous lesions to systemic disease of scleromyxedema. The clinical presentation of localized cutaneous lichen myxedematosus is waxy lichenoid papules, nodules, and/or plaques that have histopathologic findings of mucin deposition and a variable degree of fibroblast proliferation. There is an absence of serum paraproteins, and there are no other systemic causes of cutaneous mucinosis such as thyroid disease. The pathogenesis of lichen myxedematosus is unknown. We report 3 cases of localized cutaneous lichen myxedematosus with a light chain–restricted plasmacytic component by in situ hybridization. Our findings deliver an insight for disease pathogenesis and highlight for the first time, the significance of plasma cells in lesions of localized cutaneous lichen myxedematosus. We suggest that plasma cell light chain restriction could represent a clue to distinguish localized cutaneous disease from systemic disease.

A Case of Dermatitis Herpetiformis With Fibrillar Immunoglobulin A Deposition: A Rare Pattern Not to Be Missed
imageAbstract: Dermatitis herpetiformis is a rare, chronic autoimmune disorder characterized by intense pruritic papules and vesicles, which can be associated with celiac disease and other autoimmune disorders. Its histologic characteristic is the accumulation of neutrophils within the papillary dermis with granular deposition of immunoglobulin A (IgA) observed under direct immunofluorescence. Herein, we report a 58-year-old woman who presented with a vesicular rash on the buttocks. The patient reported a recent history of genital herpes, Entamoeba histolytica colitis, recurrent hives, and eczema. A representative biopsy demonstrated features of spongiotic dermatitis and focal papillary dermal neutrophilic aggregates. Direct immunofluorescence revealed fibrillary IgA deposition in the papillary dermis, granular C3 deposition at the dermal–epidermal junction, and dermal papillae. The overall clinical, histologic, and DIF findings were consistent with those of dermatitis herpetiformis. The fibrillar IgA pattern is rare and easily overlooked by the unwary. Pathologists should be aware of this rare pattern, especially when the histologic findings are not classic.

Hypopigmented Macules as Manifestation of Lichen Planus and Lichen Planopilaris
imageAbstract: Lichen planus (LP) is an idiopathic inflammatory disease of the skin, hair, nails, and mucous membranes. Classic cutaneous LP is characterized by violaceous flat-topped papules that typically favor the extremities. LP on the scalp, otherwise known as lichen planopilaris, classically presents with scarring alopecia, perifollicular erythema and follicular prominence. Although LP pigmentosus presents primarily as hyperpigmentation, there is only one previous report of hypopigmented LP. In this report, the authors report 2 cases of LP that presented primarily as hypopigmented macules in 2 African American men. The first patient presented with hypopigmented macules on face and scalp as well as trunk and extremities. The second patient presented with hypopigmented macules on scalp with associated alopecia. Histopathological examination from both patients showed features of LP. The authors propose a new variant of LP that presents acutely as hypopigmented lesions.

AL-Amyloidoma of the Skin—A Rare Manifestation of Primary Cutaneous Marginal Zone Lymphoma
imageAbstract: AL-amyloidoma is considered to be a variant of primary cutaneous marginal zone lymphoma (pcMZL). A 51-year-old white man presented a 2 × 2-cm erythematous to brownish waxy plaque on the back of the scalp. The plaque was first noticed 16 years ago. It was asymptomatic, and the patient was otherwise healthy. The lesion was excised. Histological examination revealed dermal deposits of amyloid and a subtle perivascular infiltrate, predominately consisting of plasma cells. Infiltrating cells expressed CD79a, bcl2, and IgG and were negative for bcl6, CD56, and IgM. A monoclonal light-chain expression of lambda (lambda:kappa = 10:1) was demonstrated by in situ hybridization. The diagnosis of pcMZL, presenting as an AL-amyloidoma, was made because staging procedures excluded systemic manifestation of lymphoma, monoclonal gammopathy, and systemic amyloidosis. Cutaneous amyloid deposits with monoclonal plasma cell proliferation can occur as a result of monoclonal gammopathy/plasmocytoma or as a rare manifestation of pcMZL. Systemic B-cell lymphoma and systemic monoclonal plasma cell proliferations have to be excluded.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

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