Mirror peripheral neuropathy and unilateral chronic neuropathic pain: insights from asymmetric neurological patterns in leprosy.

ABSTRACT: Leprosy-related multiple mononeuropathy offers a pattern of impairment where neuropathy with and without neuropathic pain (NeP) are present in the same individual, thus allowing to investigate peripheral sensory and innervation in both conditions. This cross-sectional study collected data on clinical and neurological examination, pain assessment questionnaires, quantitative sensory test, and intraepidermal nerve fiber density of patients with leprosy and divided the cohort into 2 groups: with NeP (P+) and without NeP (P-). Furthermore, we assessed mirror body areas in the same NeP individuals with bilateral neuropathy also presenting unilateral NeP. Pain-free patients having unilateral neuropathy were controls. A total of 37 P+ and 22 P- patients were evaluated. Limb areas with NeP had signs of C-fiber dysfunction and hyperesthesia on quantitative sensory testing compared with limb areas having neuropathy without NeP. Skin denervation was found in all patients with leprosy. Comparisons of limbs with and without neuropathy and with and without NeP revealed that higher heat pain thresholds (HPTs) were associated with neuropathic pain areas, whereas less altered HPT was correlated with higher fiber density. Furthermore, a relationship was found between time of leprosy treatment termination and more intense neuropathy, expressed by HPT increasing 0.03°C each month. As expected, interindividual comparisons failed to show differences in intraepidermal nerve fiber density and subepidermal plexus areas between P+ and P- patients ( P = 0.2980, P = 0.9044; respectively). Higher HPT and lower mechanical detection threshold were related to NeP. This study pointed out the relevance of intraindividual comparisons including mirror areas when assessing local changes in peripheral NeP.

A Severe, Refractory Case of Mucous Membrane Pemphigoid After Treatment With Pembrolizumab: Brief Communication.

Pembrolizumab is a humanized antibody that targets the programmed death-1 receptor expressed in T cells with high selectivity. This therapeutic is of great importance in cancer immunotherapy yet managing the potential immune-related adverse events remains a concern. Here, we report a rare case of mucous membrane pemphigoid in the oral mucosa, upper respiratory tract, and conjunctiva of a patient with ovarian adenocarcinoma without cutaneous manifestation, which persisted even after pembrolizumab discontinuation. A brief review of pembrolizumab-related bullous pemphigoid cases is presented and possible mechanisms underlying these lesions are discussed.

Cutaneous Metaplastic Carcinoma: Report of a Case With Sebaceous Differentiation.

In this study, a case of a 56-year-old woman with cutaneous metaplastic carcinoma in the neck is reported. It harbored basal cell carcinoma, squamous cell carcinoma, and sebaceous carcinoma, as well as osteosarcoma (with fibroblastic, osteoblastic, aneurysmal bone cyst-like, and chondroblastic patterns). To our knowledge, the literature does not mention sebaceous carcinoma in cutaneous metaplastic carcinoma. Epidemiology and intact mismatch repair proteins of this case support sporadic pathogenesis for this neoplasm. The patient has been followed up for 3 years after surgery with free margins, and no local recurrence or distant metastases have been observed.

Leiomyosarcoma of the great saphenous vein (vena saphena magna) with granular cell change: Report of a superficial neoplasm.

The great saphenous vein (GSV) corresponds to the main superficial large-caliber vessel affected by leiomyosarcoma (LMS). Given its superficial location and because signs of vascular origin may not be clinically apparent, LMS of the GSV may be misinterpreted clinically as superficial nonvascular soft tissue mass. Herein, we report a case on the distal portion of the right GSV of a 57-year-old man. The histopathological recognition of a large-caliber vein-associated LMS (with granular cell change) in an incisional biopsy specimen was crucial to guide radiological evaluation and confirmation of a superficial vascular LMS before surgical treatment. Recognizing this entity in small biopsies is important as its surgical treatment and prognosis differ substantially from nonvascular superficial (ie, subcutaneous and dermal) LMSs. In addition, because vascular LMSs can involve long vessel segments, underestimation of extent of disease is a risk. To the best of our knowledge, granular cell change has not been documented in LMS of the GSV.

Reticulated acanthoma with sebaceous differentiation mimicking melanoma.

Reticulated acanthoma with sebaceous differentiation (RASD) is a rare, benign cutaneous tumor with peculiar histopathologic characteristics [1]. RASD had been described under various synonyms such as superficial epithelioma with sebaceous differentiation, sebocrine adenoma, poroma with sebaceous differentiation, and seborrheic keratosis with sebaceous differentiation [2]. Clinical differential diagnosis of RASD includes cutaneous superficial epithelial neoplasia such as Bowen's disease, superficial basal cell carcinoma (BCC) and intraepidermal eccrine poroma [1]. We report the first case of RASD mimicking both clinically and dermoscopically a melanoma.

Extra-acral cutaneous sclerosing perineurioma with CD34 fingerprint pattern.

Sclerosing perineuroma is a variant of extraneural perineurioma that, as a rule, occurs in acral sites. However, it has also been occasionally reported in non-acral regions. Recently, CD34 expression in a pattern reminiscent of the human fingerprint has been observed in a subset of perineuriomas, but this immunohistochemical finding has not been documented in non-acral sclerosing perineuriomas. We report a case of sclerosing perineurioma presenting CD34 expression in a fingerprint-like pattern on the skin of the neck (a previously unreported site for this neoplasm) of a 56-year-old man. In addition, alpha smooth-muscle actin showed a similar pattern of expression, suggesting that the cell population implicated in the remarkable immunolabeling is most probably fibroblastic/myofibroblastic. Other immunohistochemical findings included epithelial membrane antigen and claudin1-positive lesional cells, and the absence of S100, glucose transporter protein 1, MUC4 and desmin.

Chronic reparative changes in medium-sized vessels in a case of primary cutaneous anaplastic large-cell lymphoma with angioinvasive features and cytotoxic phenotype: new histopathological findings in line with indolent clinical behavior.

Angioinvasion/angiodestruction has been reported in a small subset of primary cutaneous anaplastic large-cell lymphomas (PCALCL). Recently, PCALCL with angioinvasive features and cytotoxic phenotype has been characterized as a variant associated with good clinical outcomes despite worrisome histopathologic features. We report a case of PCALCL with angioinvasive features and cytotoxic phenotype associated with reparative changes on the wall of medium-sized vessels involved by the neoplasm, including intimal fibroblastic proliferation and luminal obliteration. This vascular pattern, although previously unreported in PCALCL, is in accordance with the indolent behavior observed in this entity and provides a further link with lymphomatoid papulosis type E.

Cutaneous lymphocytic thrombophilic (macular) arteritis: a distinct entity or an indolent (reparative) stage of cutaneous polyarteritis nodosa? Report of 2 cases of cutaneous arteritis and review of the literature.

Recently, 2 putatively novel clinicopathological entities, macular arteritis (MA) and lymphocytic thrombophilic arteritis (LTA), have been described. Both exhibit an indolent chronic course and erythematous and hyperpigmented macules (MA > LTA) and papules/plaques (LTA > MA), often in a reticulated pattern on the lower limbs. Histopathologically, they show varying degrees of lymphocyte infiltration and disruption of the arterial wall, concentric luminal fibrin deposition, and in some cases, fibrointimal scarring (endarteritis obliterans). This spectrum of histology overlaps with the subacute, reparative, and healed stages reported for cutaneous polyarteritis nodosa (CPAN). Herein, we report 2 cases of cutaneous lymphocytic arteritis, 1 with persistent indolent disease and the second with acute self-limited disease. Comparing these 2 patients' findings with that reported for MA, LTA, and CPAN highlights a clinicopathologic spectrum, which exhibits increasing disease severity moving from MA to LTA to CPAN to systemic polyarteritis nodosa. Given the clinicopathologic similarities, we conclude that our cases and cases previously reported as MA or LTA likely represent an indolent form of CPAN.

Retroperitoneal lipomatous tumors without cytologic atypia: are they lipomas? A clinicopathologic and molecular study of 19 cases.

Most well-differentiated liposarcomas can be readily distinguished from lipomas on histologic grounds alone. However, occasional retroperitoneal lipomatous tumors show no cytologic atypia. To determine whether these tumors are well-differentiated liposarcomas devoid of cytologic atypia or lipomas was the major aim of this investigation. We comprehensively and prospectively studied 19 retroperitoneal adipocytic tumors devoid of cytologic atypia at the cytogenetic and molecular genetic levels. Median patient age was 56 years (range: 36 to 78 y). Median tumor size was 21 cm (range: 8 to 46 cm) and the median weight was 1127 g (range: 173 to 2440 g). All tumors were well-circumscribed and showed no cytologic atypia. Standard cytogenetic analysis demonstrated rearrangements of 12q15 in 4 (of 7) cases. None showed ring or giant marker chromosomes. Fluorescence in situ hybridization failed to identify amplification of MDM2, carboxypeptidase M(CPM), SAS, CDK4, DDIT3, or HMGA2 in all cases. HMGA2 rearrangement was observed in 8 (of 19) cases (42%) and was more common in larger tumors (P=0.046). HMGA2-LPP fusion was seen in only 1 case. All tumors were completely excised. Follow-up information was available from 10 cases (median, 6 mo; range: 1 to 58 mo). No tumor recurred or metastasized. In contrast, a control group of 20 well-differentiated liposarcomas diagnosed during the same time period (matched per year of diagnosis) showed 4 instances of local recurrence. We conclude that this group of retroperitoneal lipomatous tumors shows clinico-pathologic and genetic features more akin to lipomas than well-differentiated liposarcomas. Owing to their apparent rarity, additional studies are necessary to more fully understand their natural biology in this anatomic location.

Dilation of apocrine glands. A forgotten but helpful histopathological clue to the diagnosis of axillary Fox-Fordyce disease.

Fox-Fordyce disease is a condition with protean histopathological alterations whose pathogenesis remains a mystery. Although recent studies have addressed histological changes specific of this disease, including perifollicular xanthomatosis, no attention has been given to apocrine acini dilation as an adjunct histopathological finding to the diagnosis. Moreover, although previous efforts were done to demonstrate that perifollicular foamy histiocytes harbor apocrine secretion content, this concept has not been proved to date. In this study, we report 2 cases harboring prominent dilation of apocrine coils with mucinous content. Such mucinous content showed mucin profile identical to the dermal mucin deposits in both cases. Of note, perifollicular foamy histiocytes demonstrated cytoplasmic mucin, supporting the suggestion that these cells phagocytose apocrine secretion. Although not specific, apocrine coil dilation is another histopathological feature of Fox-Fordyce disease and it may be used as a low-power magnification clue for the correct diagnosis. We also propose that the so-called perifollicular xanthomatosis may be composed of muciphages or mixed cell (muciphages/xanthomatous) population, an issue that should be further investigated in future studies.

Cutaneous myositis ossificans: an appropriate descriptor for fibro-osseous lesion of the external auditory canal.

Myositis ossificans is a benign pseudosarcomatous bone-forming lesion, histologically characterized by 2 components: a spindle (myo)fibroblastic cell population and a bony component that is arranged in a "zonal" pattern. It mainly affects the deep soft tissues of limbs, but its occurrence in other unusual locations, such as abdomen, inside nerves, and the subcutaneous fat, has been reported. The existence of myositis ossificans restricted to the skin has rarely been published under the term "fibro-osseous lesion of the external auditory canal." Here, we describe an additional case in the external auditory canal, emphasizing its differential diagnosis and alerting dermatopathologists and pathologists to the possibility of encountering such lesion in this anatomic location. For purposes of unifying terms, we propose that cases similar to ours be called "cutaneous myositis ossificans" instead of fibro-osseous lesion of the external auditory canal.

Salivary gland-type lung carcinomas: an EGFR immunohistochemical, molecular genetic, and mutational analysis study.

Salivary gland-type lung carcinomas are uncommon neoplasms of the lung, the two most common being adenoid cystic carcinoma and mucoepidermoid carcinoma. Although they usually have an indolent behavior, adenoid cystic carcinomas can be more aggressive, with 5-year survival as low as 55%. Unfortunately, these tumors do not respond well to chemotherapy. In contrast to the most common subtypes of lung carcinomas, epidermal growth factor receptor studies have not been carried out in this group of tumors. Herein we report a series of 24 cases (12 adenoid cystic and 12 mucoepidermoid carcinomas) tested for epidermal growth factor receptor protein expression, epidermal growth factor receptor gene copy gains, and epidermal growth factor receptor gene mutational status, through immunohistochemistry, fluorescence in situ hybridization, and sequencing of the exons 18-21, respectively. Overall, 91 and 92% of the adenoid cystic carcinomas and mucoepidermoid carcinomas expressed epidermal growth factor receptor protein. Chromosome 7 polysomy occurred in 25% of the cases (four adenoid cystic carcinomas and two mucoepidermoid carcinomas). No epidermal growth factor receptor gene amplification was detected and no mutation was found in exons 18-21 of the epidermal growth factor receptor gene. Immunoexpression of epidermal growth factor receptor in salivary gland-type lung carcinomas is not related to epidermal growth factor receptor gene copy number or mutational status.

Cutaneous lipomatous sclerosing perineurioma.

Sclerosing perineurioma is a variant of extraneural soft tissue perineurioma that occurs in the distal extremities of young adults. They are composed of small, plump, spindle-shaped, or epithelioid perineurial cells that coexpress epithelial membrane antigen (EMA), glut-1, claudin 1, collagen type IV, laminin, and are negative for S-100 protein. Once locally excised, sclerosing perineurioma does not recur or metastasize. Adipocytic component has been observed occasionally in peripheral nerve sheath tumors. In particular, only one report has previously detailed histopathological features of a superficial soft tissue perineurioma harboring lipomatous areas. Herein, we report a unique case of sclerosing perineurioma showing adipocytic component. Knowledge of this phenomenon is important to reach a correct diagnosis and to avoid unnecessary aggressive local excision.

Genomic gains of COL1A1-PDFGB occur in the histologic evolution of giant cell fibroblastoma into dermatofibrosarcoma protuberans.

Giant cell fibroblastoma (GCF) is a subcutaneous mesenchymal neoplasm characterized by the chromosomal t(17;22), which results in the formation of the fusion gene COL1A1-PDGFB. This same fusion gene is also seen in the supernumerary ring chromosome of dermatofibrosarcoma protuberans (DFSP). Several studies have addressed the molecular genetics of DFSP but molecular cytogenetic characterization of individual areas and cell components in pure GCF and GCF/DFSP hybrids have not been performed. Herein, we studied the frequency and genomic copy number of COL1A1-PDGFB in pure GCF and GCF/DFSP hybrids, and identified the molecular cytogenetic signatures in individual cells in each component. Four pure GCF and nine GCF/DFSP hybrids were studied. All tumors exhibited classical histological features and CD34 expression. COL1A1 and PDGFB rearrangements were evaluated by fluorescence in situ hybridization (FISH) using probes for COL1A1 and PDGFB on paraffin-embedded thin tissue sections. All GCF and GCF/DFSP hybrids showed unbalanced rearrangements of COL1A1-PDGFB at the molecular cytogenetic level. Genomic gains of COL1A1-PDGFB were found predominantly in the DFSP component of GCF/DFSP hybrids but in none of the pure GCF, suggesting that these gains are associated with the histologic evolution of GCF into DFSP. The molecular cytogenetic abnormalities were found not only in the spindle/stellated cells but also in individual nuclei of the multinucleated giant cells, suggesting that these cells may result from the fusion of individual neoplastic cells.

Perineurioma: a distinctive and underrecognized peripheral nerve sheath neoplasm.

CONTEXT: Perineuriomas are benign peripheral nerve sheath neoplasms composed of perineurial cells with characteristic immunohistochemical and ultrastructural features. They have been traditionally classified into two main types according to their location--intraneural and extraneural--and overlap histologically with many other tumors, which may be diagnostically challenging to general surgical pathologists. OBJECTIVE: To review the clinical, morphologic, immunohistochemical, ultrastructural, cytogenetic, and molecular genetic aspects of perineurioma, as well as to discuss its clinicopathologic variants and differential diagnosis. DATA SOURCES: English-language literature published between 1966 and 2005 was reviewed. CONCLUSIONS: The correct identification of perineuriomas is important to avoid unnecessary overtreatment. The histologic diagnosis should be confirmed through immunohistochemical studies (including epithelial membrane antigen, S100 protein, and more recently described antibodies such as claudin-1 and GLUT1) or electron microscopy. Cytogenetic and molecular genetic studies are still of limited value for the diagnosis of perineuriomas but may play a fundamental role in excluding important differential diagnoses and also in helping elucidate the biology of these poorly known neoplasms.

Cytogenetic and molecular cytogenetic findings in dedifferentiated liposarcoma with neural-like whorling pattern and metaplastic bone formation.

Dedifferentiated liposarcoma is a subtype of liposarcoma characterized by juxtaposition of well-differentiated liposarcoma with a nonadipocytic sarcoma. A peculiar form of dedifferentiated liposarcoma has been described, characterized by a nonlipogenic component with a neural-like whorling pattern of growth and metaplastic bone formation. We report the cytogenetic and molecular genetic findings of this peculiar form of dedifferentiation in a retroperitoneal tumor found in a 58-year-old female. The neoplasm had typical histologic findings and a complex karyotype characterized by several numeric and structural chromosomal abnormalities, including the presence of ring and giant rod chromosomes. Molecular cytogenetic studies found high levels of amplification of the MDM2 oncogene, consistent with the amplification of the 12q14 chromosome band, a cytogenetic abnormality commonly found in these tumors. These findings indicate that, despite its unique and peculiar morphologic features, this unusual type of dedifferentiated liposarcoma shares many of the cytogenetic features and molecular genetic abnormalities found in other forms of dedifferentiation. The specific cytogenetics and molecular determinants of these peculiar morphologic findings, however, remain unknown.

Cytogenetic and molecular genetic findings in dedifferentiated liposarcoma with neural-like whorling pattern and metaplastic bone formation.

Dedifferentiated liposarcoma, a subtype of liposarcoma, is characterized by juxtaposition of well-differentiated liposarcoma with a nonadipocytic sarcoma. A peculiar form of dedifferentiated liposarcoma has been described, characterized by a nonlipogenic component with a neural-like whorling pattern of growth and metaplastic bone formation. We report the cytogenetic and molecular genetic findings of this peculiar form of dedifferentiation in a retroperitoneal tumor found in a 58-year-old woman. The neoplasm had the typical histologic findings and a complex karyotype characterized by several numeric and structural chromosome abnormalities, including the presence of ring and giant rod chromosomes. Molecular genetic studies found high levels of amplification of the MDM2 oncogene, consistent with the amplification of the 12q14 chromosome band, a cytogenetic abnormality commonly found in these tumors. These findings indicate that, despite its unique and peculiar morphologic features, this unusual type of dedifferentiated liposarcoma shares many of the cytogenetic and molecular genetic abnormalities found in other forms of dedifferentiation. However, the specific cytogenetic and molecular determinants of these peculiar morphologic findings remain unknown.

Angiolymphoid hyperplasia with eosinophilia showing prominent granulomatous and fibrotic reaction: a morphological and immunohistochemical study.

Angiolymphoid hyperplasia with eosinophilia is an uncommon condition that usually presents in early to middle-aged adults as multiple red nodules or plaques, most commonly on the head and neck. It can also occur on the trunk and limbs, and rarely at other sites such as the breast and oral mucosa. Although one-third of these lesions recur, surgical excision is curative. The histopathological hallmark is the presence of blood vessels with plump epithelioid endothelial cells. The nonvascular component consists of histiocytes, plasma cells, eosinophils, and lymphocytes. The occurrence of numerous giant cells in the stroma of angiolymphoid hyperplasia with eosinophilia is extremely unusual and such a finding in association with diffuse granulomatous/fibrous reaction has not been reported. We describe such a lesion that developed in the wrist of a 34-year-old pregnant female.