Dermatopathology

Mycosis fungoides (MF) is a subtype of primary cutaneous T-cell lymphoma (CTCL) with an indolent course that rarely progresses. Histologically, the lesions display a superficial lymphocytic infiltrate with epidermotropism of neoplastic T-cells. Hypopigmented MF is a rare variant that presents with hypopigmented lesions and is more likely to affect young patients. The etiology of the hypopigmentation is unclear. The aim of this study was to assess melanocyte loss in MF through immunohistochemistry (IHC) with SOX10. Twenty cases were evaluated, including seven of the hypopigmented subtype. The neoplastic epidermotropic infiltrate consisted predominantly of CD4+ T-cells in 65% of cases; CD8+ T-cells were present in moderate to abundant numbers in most cases. SOX10 IHC showed a decrease or focal complete loss of melanocytes in 50% of the cases. The predominant neoplastic cell type (CD4+/CD8+), age, race, gender, histologic features, and reported clinical pigmentation of the lesions were not predictive of melanocyte loss. A significant loss of melanocytes was observed in 43% of hypopigmented cases and 54% of conventional cases. Additional studies will increase our understanding of the relationship between observed pigmentation and the loss of melanocytes in MF. Full article

Animal-type melanoma (ATM) was first described in the literature by Levene in 1979 in relation to a patient with a characteristic clinical presentation, and only later, rare and anecdotal case series have tried to shed light on an entity that has undergone several nosographic classification changes, and which, since 2018, is classified under the term “pigmented epithelioid melanocytoma”. Here, we conduct a brief review of the current literature on ATM and present a new clinical case with histopathological, immunophenotypic, and molecular investigations. Full article

Trichoblastoma (TB) is a rare biphasic benign adnexal neoplasm originating from follicular germ cells but clinically, it can simulate basal cell carcinoma (BCC), making the diagnosis more difficult. There are several variants of Trichoblastoma and a good knowledge of these is essential for correct diagnosis and management. We report two new cases observed in the last year at our Pathological Anatomy Operative Unit, and conduct a careful review of the literature, from the first description of this lesion by Headington in 1970 to the most recent classifications. Full article

GLUT1 is a membrane associated carrier protein that functions in the physiologic transport of glucose across cell membranes. Multiple studies have shown an increased GLUT1 expression in various tumor types and a role in cancer prognosis. The aim of this study was to determine whether cutaneous sebaceous lesions have a differential expression of GLUT1 by immunohistochemistry (IHC). GLUT1 IHC was performed on excision specimens of ten cases of sebaceous carcinoma, nine of sebaceoma, ten of sebaceous adenoma, and ten of sebaceous hyperplasia. Intense, diffuse cytoplasmic staining was observed in sebaceous carcinoma. The pattern of GLUT1 staining in sebaceomas and sebaceous adenomas consisted of a gradient of intense cytoplasmic staining in the basaloid cells with a decreased intensity to membranous staining only and absent staining in mature sebaceous cells. In lesions of sebaceous hyperplasia, GLUT1 staining outlined the basal layer of each gland; cytoplasmic staining was minimal to absent. Increased cytoplasmic staining of GLUT1 may correlate with cellular metabolic and proliferative activity. GLUT1 has potential utility in differentiating sebaceous lesions. Full article

Collision tumors consisting of melanoma and squamous cell carcinoma are very rare. We present the case of a deceptive hyperkeratotic nodule on the forearm of a 72-year-old woman, which clinically appeared to be a squamous cell carcinoma, keratoacanthoma type. Histological examination surprisingly revealed a coexisting epithelioid melanoma. Thus, this case report shows the importance of an early histopathological and immunohistochemical workup to prevent unnecessary diagnostic and therapeutic delay with negative effects on prognosis. Full article

Tuberous Sclerosis Complex (TSC) is a multisystem genetic disease characterized by cutaneous and extracutaneous hamartomas. The diagnosis is based on the association of major and minor criteria, defined by a consensus conference updated in 2012. The clinical examination of the skin is crucial because seven diagnostic criteria are dermatological: four major (hypomelanotic macules, angiofibroma or fibrous cephalic plaques, ungual fibromas, shagreen patches) and three minor criteria (confetti skin lesions, dental enamel pits, intraoral fibromas). Skin biopsy is commonly performed to assert the diagnosis of TSC when the clinical aspect is atypical. Histopathology of TSC cutaneous lesions have been poorly reported until now. In this article, we review the histologic features described in the literature and share our experience of TSC skin biopsies in our pediatric hospital specialized in genetic disorders. Both hypomelanotic lesions and cutaneous hamartomas (angiofibroma/fibrous cephalic plaques, ungual fibromas, shagreen patches) are discussed, including the recent entity called folliculocystic and collagen hamartoma, with a special emphasis on helpful clues for TSC in such lesions. Full article

Primary localized cutaneous nodular amyloidosis (PLCNA) is a rare condition due to the plasma cell proliferation and skin deposition of immunoglobulin light chains, without systemic amyloidosis or hematological dyscrasias. The association with autoimmune connective tissue diseases has been reported, especially with Sjogren’s syndrome, and in a few cases with systemic sclerosis. Herein, we describe three cases of PLCNA occurring in women with a diagnosis of limited cutaneous systemic sclerosis and review the literature on the topic to highlight a stereotypical presentation. Moreover, we support the usefulness of dermoscopy, characterized by a yellow–orange waxy pattern surrounded by telangiectasias, for a rapid and non-invasive diagnostic assessment. Thus, when asymptomatic nodules occur on lower limbs of women affected with limited systemic sclerosis, and dermoscopy identifies yellow–orange blotches, a diagnosis of PLCNA can be considered and further confirmed by histopathology. Monitoring for systemic amyloidosis development is advisable, although the risk of progression is considered very low. Full article

Primary cutaneous γδ T-cell lymphoma (PCGD-TCL) is an extremely rare and aggressive T-cell neoplasm with complex heterogeneity. We present a series of two patients who presented with firm, subcutaneous nodules and were diagnosed with PCGD-TCL. In both cases, biopsies demonstrated a both superficial and deep adnexotropic infiltrate comprised of angiocentric, medium- to large-sized atypical lymphocytes. The infiltrate extended into the panniculus. Immuno–histochemical stains highlighted atypical lymphocytes that expressed CD3, CD8 and CD56 but were negative for EBV ISH. A brisk histiocytic response with focal aggregation into granulomas was highlighted with a PG-M1 stain. The atypical lymphocytes were positive for gene rearrangements on a TCR delta stain and negative for βF-1. CT and PET scan in one of the two patients demonstrated diffuse, subcutaneous, ground-glass foci; hypermetabolic soft tissue nodules; and lymphadenopathy in the lungs, as well as splenomegaly. A diagnosis of histiocyte-rich PCGD-TCL was rendered. A histiocyte-rich, granulomatous variant of γδ T-cell lymphoma is extremely rare. Its potentially misleading resemblance to inflammatory granulomatous conditions could pose a diagnostic pitfall in this already challenging condition. This variant may resemble granulomatous mycosis fungoides and granulomatous slack skin syndrome, but it has a distinct, aggressive clinical outcome. Full article

Autoinflammation is defined by aberrant, antigen-independent activation of the innate immune signaling pathways. This leads to increased, pro-inflammatory cytokine expression and subsequent inflammation. In contrast, autoimmune and allergic diseases are antigen-directed immune responses from activation of the adaptive immune system. The innate and adaptive immune signaling pathways are closely interconnected. The group of ‘complex multigenic diseases’ are a result of mutual dysregulation of both the autoinflammatory and autoimmune physiologic components. In contrast, monogenic autoinflammatory syndromes (MAIS) result from single mutations and are exclusively autoinflammatory in their pathogenesis. Studying the clinical and histopathological findings for the various MAIS explains the phenotypical correlates of their specific mutations. This review aims to group the histopathologic clues for autoinflammation into three recognizable patterns. The presence of these histologic patterns in a pediatric patient with recurrent fevers and systemic inflammation should raise suspicion of an autoinflammatory component in MAIS, or, more frequently, in a complex multigenic disease. The three major histopathological patterns seen in autoinflammation are as follows: (i) the ‘neutrophilic’ pattern, seen in urticarial neutrophilic dermatosis, pustular psoriasis, aseptic neutrophilic folliculitis, and Sweet’s syndrome; (ii) the ‘vasculitic’ pattern seen in small vessel-vasculitis (including hypersensitivity/leukocytoclastic vasculitis, thrombosing microangiopathy and lymphocytic vasculitis), and intermediate-sized vessel vasculitis, mimicking polyarteritis nodosa; and (iii) the ‘granulomatous’ pattern. Beyond these three patterns, there are additional histopathologic clues, which are detailed below. It is important for a dermatopathologist to recognize the patterns of autoinflammation, so that a diagnosis of MAIS or complex multigenic diseases may be obtained. Finally, careful histopathologic analyses could contribute to a better understanding of the various clinical manifestations of autoinflammation. Full article

Background: The association between Merkel cell carcinoma (MCC) and chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL) is well established in the literature. A majority of MCCs are known to be associated with Merkel cell carcinoma polyomavirus (MCPyV), which is postulated to be a possible causative agent linking these two entities. We aim to identify the presence of MCPyV in patients with concurrent adjacent MCC and CLL/SLL. Methods: Archived pathology materials of three cutaneous or surgical excisions with concurrent MCC and CLL/SLL were reviewed. Additional 12-µm sections from paraffin-embedded tissue of these resections were matched with original hematoxylin and eosin-stained slides and used to extract foci from each tumor separately. DNA was extracted from these tissues, and polymerase chain reaction (PCR), utilizing a primer set within a highly conserved “small T” viral DNA region, was done to detect MCPyV. Results: Out of 140 cases of cutaneous or surgical excisions with MCC identified in our electronic medical records (EMR), three had coexisting neighboring CLL/SLL in the same resection specimen. In one case out of three, MCPyV was detected in MCC but not in CLL/SLL. The remaining two cases showed no detection of MCPyV in either MCC or CLL/SLL. Conclusion: MCPyV was not concurrently associated with adjacent MCC and CLL/SLL, indicating that it is not driving simultaneous tumorigenesis, at least in a subset of these cases. Full article

A 64-year old male presented with a several-year history of an insidious-onset tender, itchy and xerotic rash on his lower legs. Past medical history was significant for Graves’ disease and Graves’ ophthalmopathy. The examination revealed peau d’orange-appearing plaques on his shins clinically consistent with pretibial myxedema. A punch biopsy showed separation of collagen bundles with extensive dermal mucin deposition, confirming the diagnosis of pretibial myxedema. After initially failing treatment with a topical clobetasol 0.05% ointment, the patient switched to regular pentoxifylline and triamcinolone 0.1% ointment under occlusion. He remains under follow-up. Full article

Aims: Conjunctival and cutaneous melanoma partially share similar clinical and molecular backgrounds. As 5-hydroxymethylcytosine (5-hmC) loss has been demonstrated in cutaneous melanoma, we decided to assess if similar changes were occurring in conjunctival melanoma. Methods: 5-methylcytosine (5-mC), 5-hmC and TET2 were respectively identified by immunohistochemistry and RNA ISH in 40 conjunctival nevi and 37 conjunctival melanomas. Clinicopathological correlations were established. Results: 5-mC, TET2 and 5-hmC were respectively identified in 67.5%, 95% and 100% of conjunctival nevi and in 81.1%, 35.1% and 54% of conjunctival melanomas. A significant 5-hmC and TET2 loss was identified in conjunctival melanoma comparing to nevus, as well as a significant correlation between TET2 and 5-hmC expression. In the melanomas, 5-hmC expression was only significantly associated with local lymphatic invasion, but not with other clinicopathological parameters. There was a correlation between TET2 expression and the localization of the tumors. 5-mC expression was not associated with any clinicopathological parameters. Conclusions: We identified a significant 5-hmC loss in conjunctival melanoma similar to cutaneous melanoma. This loss may possibly be attributed to TET2 loss or IDH1 mutations. 5-hmC loss in conjunctival melanoma may help in the differential diagnosis between atypical conjunctival nevus and conjunctival melanoma. Full article

The onset of blisters in a neonate or an infant is often a source of great concern for both parents and physicians. A blistering rash can reveal a wide range of diseases with various backgrounds (infectious, genetic, autoimmune, drug-related, traumatic, etc.), so the challenge for the dermatologist and the pediatrician is to quickly determine the etiology, between benign causes and life-threatening disorders, for a better management of the patient. Clinical presentation can provide orientation for the diagnosis, but skin biopsy is often necessary in determining the cause of blister formations. In this article, we will provide information on the skin biopsy technique and discuss the clinical orientation in the case of a neonate or infant with a blistering eruption, with a focus on the histology for each etiology. Full article

Proliferating trichilemmal tumours (PTT) are defined by a benign squamous cell proliferation inside a trichilemmal cystic (TC) cavity. A possible explanation of this proliferative phenomenon within the cyst may be molecular alterations in genes associated to cell proliferation, which can be induced by ultraviolet radiation. Among other genes, alterations on TP53 and DNA mismatch repair proteins (MMR) may be involved in the cellular proliferation observed in PTT. Based on this assumption, but also taking into account the close relationship between the sebaceous ducts and the external root sheath where TC develop, a MMR, a p53 expression assessment and a TP53 study were performed in a series of 5 PTT cases, including a giant one. We failed to demonstrate a MMR disorder on studied PTT, but we agree with previous results suggesting increased p53 expression in these tumours, particularly in proliferative areas. TP53 alteration was confirmed with FISH technique, demonstrating TP53 deletion in most cells. Full article

The interface dermatitides encompass a vast array of cutaneous entities which, at times, may present with particular clinical variants with adnexal predilection. Similarly, hair follicle and eccrine gland involvement of some of these entities has been observed on histopathology. This review aims to describe the various adnexotropic presentations of the interface dermatitides. Recognizing that the adnexa can be a frequent site of involvement of these conditions may aid dermatopathologists in making the correct diagnosis and avoid misinterpreting adnexotropism for other conditions such as the great imitator, mycosis fungoides. Full article

Melanoma is among the most aggressive tumors, with different histological patterns of presentation ranging from the usual and easily diagnosable pictures to complex patterns of difficult diagnostic interpretation. Here, we present three cases of a very rare melanoma variant described as “carcinoid-like” and “paraganglioma-like” in the literature, and a brief review of the current literature of the very few cases described to date. Full article

Lymphocytic infiltration of the skin (LIS), first reported by Jessner and Kanof in 1953, is a disease of unknown etiology characterized by erythematous papules and plaques on the head, neck, and upper back and histopathological findings of a normal epidermis with underlying lymphocytic infiltration of the reticular dermis without mucin deposition. A 69-year-old man and a 21-year-old woman presented with edematous indurative erythema of the left upper eyelid. Lymphocytic infiltration of the dermis with CD4+ T cell predominance was noted on biopsy. A 68-year-old man presented with a four-year history of recurrent edematous indurative erythema of the right upper eyelid that extended up to the right cheek. Predominantly dermal infiltration of CD8+ T lymphocytes was found on biopsy. We treated all three patients with 8–16 mg of methylprednisolone daily, and the erythema and induration improved. CD4+ T cells were predominant in the acute phase (patients 1 and 2), whereas CD8+ T cells were predominant in the chronic phase (patient 3). CD8+ T cells may be involved in LIS recurrence. Lymphocytic infiltration of the eyelid may be associated with isolated circumscribed, edematous, indurative, colorless lesions that are responsive to daily low-to-middle doses of oral methylprednisolone. Full article

Ichthyoses are inborn keratinization disorders affecting the skin only (non-syndromic) or are associated with diseases of internal organs (syndromic). In newborns, they can be life-threatening. The identification of the gene defects resulted in reclassification and a better understanding of the pathophysiology. Histopathologic patterns include orthohyperkeratosis with a reduced or well-developed stratum granulosum, hyperkeratosis with ortho- and parakeratosis with preserved or prominent stratum granulosum, and epidermolytic ichthyosis. Another pattern features “perinuclear vacuoles and binucleated keratinocytes”, which is associated with keratin mutations. Some ichthyoses are histologically defined by psoriasis-like features, and distinct subtypes show follicular hyperkeratosis. In addition to histological and immunohistochemical methods, these patterns allow a better histopathologic diagnosis. Full article

Smooth muscle hamartoma are usually solitary and congenital, may affect the genital area and nipples. Histopathologically, they are characterized by the presence of mature smooth muscle bundles. We present a 40 year-old male with bilateral nipple enlargement excised with clinical suspicion of bilateral leiomyoma. Skin biopsy shows mature, irregularly arranged smooth muscle bundles and lactiferous ducts between them. Immunohistochemistry is positive for smooth muscle actin, desmin and fumarase, but negative for estrogen and progestogen receptors. The presence of lactiferous ducts excludes bilateral leiomyomas. Even when, histopathologically, this can be interpreted as the nipple-type of muscular hamartoma of the breast, clinical history favors an anabolic drug-induced lesion. Bodybuilders present gynecomastia and nipple enlargement as frequent problems, but we have not found any histopathological description of these nipple lesions. We consider that dermatologists should be aware of the presence of them and dermatopathologists should know their histopathological features to avoid misdiagnosis as neoplasms. Full article