Sweat duct proliferation associated with aggregates of elastic tissue and atrophodermia vermiculata: a simulator of microcystic adnexal carcinoma. Report of two cases†

Microcystic adnexal carcinoma (MAC) is a rare, usually solitary, slowly growing, yet aggressive neoplasm with a tendency for local recurrences. Herein, we present two patients who had been histopathologically diagnosed as suffering from MAC on both cheeks since childhood, an unlikely scenario. Both from a clinical and from a histopathological point of view, our two cases showed some similarities with those previously described in patients with Nicolau‐Balus syndrome, Rombo syndrome, and so‐called eccrine‐pilar hamartoma. Common to all these latter disorders are the round aggregations of elastic tissue in the papillary dermis, a histopathological feature which was also found in our patients. However, to our knowledge, the presence of a MAC‐like ductal proliferation embedded in sclerotic stroma and extending to the deep dermis has not been previously described. Dermatologists and dermatopathologists should be aware of this disorder to avoid overdiagnosis of and inappropriate treatment for MAC. Schaller J, Rytina E, Rütten A, Hendricks C, Ha T, Requena L. Sweat duct proliferation associated with aggregates of elastic tissue and atrophodermia vermiculata: a simulator of microcystic adnexal carcinoma. Report of two cases.     

Apocrine intraductal carcinoma in situ in nevus sebaceus: two case reports

Ductal carcinoma in situ (DCIS) in the mammary glands consists of a proliferation of ductal luminal cells with preserved polarity but lacking the marked intercellular cohesion of hyperplastic cells. We report two cases of DCIS arising in the apocrine glandular structures of a nevus sebaceus (NS). The first patient was a 44‐year‐old woman with a ductal neoplasm composed of multilayered ductal elements with a monomorphous cellularity and a polar orientation of nuclei. The neoplastic cells were positive for Cm5.2 and CK7. The second patient was a 67‐year‐old woman with phacomatosis pigmentokeratotica. A skin biopsy of an erythematous plaque within her NS showed an epithelioid monomorphous tumor with eosinophilic and slightly granular cytoplasm. Slight nuclear pleomorphism with some hyperchromatic nuclei was seen. The tumor cells were positive for CK7 and gross cystic disease fluid protein‐15. Actin showed a preserved layer of myoepithelial cells in both cases. Our cases are noteworthy, as secondary malignancies or multiple tumors arising in NS are rare, and the presence of multiple neoplasms in phacomatosis pigmentokeratotica is even rarer. Moreover, these tumors expand the spectrum of secondary malignant neoplasms arising in NS, as they closely resemble mammary DCIS.     

Malignant melanoma cells in the eccrine apparatus

A case of malignant melanoma arising on the sole of a 75-year-old Japanese man is presented. Histopathologically, in addition to the intraepidermal and intradermal malignant melanoma cells reaching the upper part of the dermis, cells were also found in the deep part of the ductal epithelium of the eccrine apparatus. Melanoma cells, and melanocytic nevus cells as well, are rarely found within the epithelial structure of sweat glands, yet they are frequently found in that of hair follicles. In order to avoid a residue of melanoma cells in the deep part of the eccrine apparatus, a fairly deep excision should be performed even for this melanoma.     

A case of porocarcinoma arising in pigmented hidroacanthoma simplex with multiple lymph node,liver and bone metastases

Porocarcinoma is a rare skin appendage carcinoma that may arise de novo or be associated with pre‐existing poroma and hidroacanthoma simplex (HAS). Here, we report a case of porocarcinoma arising in pigmented HAS, which led to death from multiple lymph node, liver and bone metastases. A 72‐year‐old Japanese man presented with a brown to focal black flat plaque, measuring 17 × 12 mm, on the posterior region of his right thigh. Histopathological study of the tumor revealed that there was intraepidermal proliferation of small‐sized basaloid cells, and it exhibited the ‘Jadassohn phenomenon’, with dendritic melanocytes, and a few ductal structures were observed. Continuing to the intraepidermal nests, the invasive proliferation of large polygonal cells with occasional intracytoplasmic ductal structures was observed. Carcinoembryonic antigen and epithelial membrane antigen were expressed in some carcinoma cells and they highlighted the intracytoplasmic ductal structures. Multiple lymph node, liver and bone metastases were observed, and the patient died 8 months after the initial surgery. Clinical diagnosis of HAS is extremely rare. Porocarcinoma may be associated with pre‐existing HAS and sometimes shows aggressive behavior. Therefore, pigmented HAS must be included in the differential diagnosis of brown or black lesions. Ishida M, Hotta M, Kushima R, Okabe H. A case of porocarcinoma arising in pigmented hidroacanthoma simplex with multiple lymph node, liver and bone metastases.     

In situ carcinoma in a hybrid cyst: a case report

Follicular hybrid cysts including two or more components of the epithelial skin adnexa are very rare. The epithelial lining of hybrid cysts varies, and either contains epidermis, and trichilemmal squamous epithelium, or other epithelia of the skin adnexa. Hybrid cysts may also be associated with neoplasia, such as in situ carcinoma, Bowen's disease and squamous cell carcinoma. A 37‐year‐old female was complaining of a cyst on her scalp. The unilocular cystic lesion was lined with markedly atypical squamous cells with trichilemmal differentiation. Marked nuclear and cytological atypia, pleomorphism, numerous mitotic figures and atypical mitosis was detected in the squamous epithelium. The epithelium of the cyst was also composed of ductal structures lined with cuboidal epithelium. Immunohistochemical staining was positive for cytokeratin 7 (CK7) in both squamous and glandular epithelium. Luminal staining was shown by carcinoembryonic antigen (CEA), although gross cystic disease fluid protein‐15 (GCDFP‐15) was negative in the glandular epithelium. In addition, p16 tumor suppressor gene was strongly positive in both the squamous and glandular epithelium. Overall, the unique cystic lesion reported contained pilar squamous epithelium with in situ carcinoma and eccrine ductal structures, which was interpreted as a hybrid cyst composed of in situ trichilemmal carcinoma and a ductal eccrine component.     

Reversed cellular polarity in primary cutaneous mucinous carcinoma: A study on tight junction protein expression in sweat gland tumors

Primary cutaneous mucinous carcinoma (PCMC) is a rare sweat gland tumor characterized by the presence of abundant mucin around the tumor islands, but the molecular mechanisms for this structure are not well elucidated. Because mucin is epithelial in nature, it is likely to be produced by epithelial tumor cells, not by surrounding stromal cells. We hypothesized that the abundant mucin is a result of reversed cellular polarity of the tumor. To test this hypothesis, we conducted an immunohistological study to investigate expression of tight junction (TJ) proteins occludin and ZO‐1 in PCMC, as well as in normal sweat glands and other sweat gland tumors. Dot‐like or linear expression of TJ proteins was observed at ductal structures of sweat glands, and ductal or cystic structures of related tumors. In PCMC, however, TJ protein expression was clearly visible at the edges of tumor cell islands. This study provides evidence to show that the characteristic histological structure of PCMC is caused by inverse polarization of the tumor cells, and that TJ proteins are useful markers of ductal differentiation in sweat gland tumors.     

Mohs micrographic surgery in the treatment of microcystic adnexal carcinoma

Microcystic adnexal carcinoma is a rare neoplasm with a propensity for slow growth and extensive local invasion. Pathology is characterized by multiple islands of basaloid epithelial cells, ductal structures, and keratinizing cysts, located intradermally but often extending deep as thin strands of tumor cells intercalating between collagen bundles. Perineural and intramuscular invasion are common. Treatment with Mohs surgery allows for fewer procedures with increased likelihood of long-term cure and tissue conservation.     

Benign mixed tumor of the skin,hypercellular variant: a case report

A 71‐year‐old man presented with a slowly growing 2.0×2.0×1.0 cm scalp lesion that was surgically removed. Microscopic examination showed a well‐circumscribed dermally located tumor composed of ductal elements lined by double to multiple cell layers of bland cuboidal inner cells and elongated spindled outer cells with areas showing cribriform and solid growth patterns. Some cells showed prominent cytoplasmic clearing. A few mitotic figures are noted ranging from 1‐2 mitotic figure/10 hpf. There are also foci of squamous differentiation as well as occasional mature adipocytes. The background stroma was predominantly sclerotic with only small area of myxoid background (confirmed by Hale's colloidal iron). Immunohistochemical studies revealed positive immunoreactivity for EMA, CEA, CD117, HWMK, LWMK, CK7, Androgen receptor and S100 in the ductal (epithelial) cells and positive immunereactivity for calponin, SMA, CK 5/6 and p63 in the myoepithelial component. No immunoreactivity for Brst‐2, ER, PR and CK20 was noted. MIB‐1 showed mildly increased proliferrative index highlighting 5% of the nuclei. The overall morphology and immunohistochemical profile are that of a benign cutanoues mixed tumor (chondroid syringoma). Given the unusual striking celluarlity, we suggest to subclassify this as a hyper‐cellular variant. Hafezi‐Bakhtiari S, Al Habeeb A, Ghazarian D. Benign mixed tumor of the skin, hypercellular variant: a case report.     

Xerostomia in Sjögren's syndrome and lupus erythematosus: a comparative histological and immunofluorescence study of minor salivary glands alterations

Background: Xerostomia is a symptom that can be triggered by chronic diseases such as Sjögren's syndrome (SS) and lupus erythematosus (LE). Many authors regard most cases of salivary hypofunction in LE to secondary SS. Others believe that salivary changes in patients with LE might reflect a multisystem presentation of the disease. The present study compared histopathological and direct immunofluorescence (DIF) alterations in salivary glands of patients with xerostomia and diagnosis of LE or SS. Methods: Twenty‐eight salivary gland biopsies from patients with xerostomia and diagnosed with LE or SS were submitted to histopathological and DIF exams. Results: From the 28 patients, 16 had SS and 12 had LE. In SS, a moderate to intense sialadenitis was detected, with infiltration and destruction of excretory salivary ducts. In LE, mild/moderate sialadenitis with thickening and hyalinization of the ductal basement membrane was observed. DIF revealed that 50% of SS patients presented intercellular ductal IgA deposits, whereas 58% of LE patients showed deposits of IgG in the ductal basement membrane. Conclusions: Alterations in salivary glands of LE patients may be a specific manifestation of the disease (lupus sialadenitis), reflecting its multisystemic presentation, instead of an association of secondary SS and LE. Fernandes JD, Nico MMS, Aoki V, Bologna S, Romiti R, Levy‐Neto M and Lourenço SV. Xerostomia in Sjögren's syndrome and lupus erythematosus: a comparative histological and immunofluorescence study of minor salivary glands alterations.     

Pilary Complex Carcinoma: An Adnexal Carcinoma of the Skin with Differentiation towards the Components of the Pilary Complex

We report twelve cases with a distinctive form of adnexal carcinoma occurring most commonly over the head and neck of relatively old individuals. The growth was single in all cases, deep dermal in location, and consisted of massive proliferation of small basaloid cells with only occasional connection with the surface epidermis. The basaloid tumor masses showed only a few areas of palisading of their outer cell nuclei and occasional retraction space formation. The neoplasm revealed scattered areas of trichilemmal and epidermoid keratinization, foci of sebaceous, and areas of sweat ductal differentiation indicating participation of various components of the pilary complex.     

A unique case of apocrine carcinoma on the male pubic skin: Histopathologic and ultrastructural observations

We report a case of cutaneous adenocarcinoma on the pubic region of a 56-year-old male. The exophytic tumor showed solid, ductal, and glandular patterns with decapitation secretion and mucinous carcinoma-like nests. Despite the exophytic nature of the lesion, an invasive growth pattern into the deep dermis and subcutaneous fat was seen. An additional characteristic of this tumor was the presence of Paget's phenomenon. From these findings, we conclude that this tumor is an apocrine adenocarcinoma having an unusual clinical appearance and unique histopathological features which have some similarities to apocrine carcinoma of the breast and some to syringocystadenoma papilliferum and nipple adenomatosis.     

Expression and localization of Artemis serine 516 phosphorylation in human scalp skin

Artemis phosphorylation at serine 516 (Ser516) has important regulatory functions in the repair of radiation‐induced DNA damage, V(D)J recombination, p53‐dependent apoptosis and cell cycle control. Accordingly, Artemis mutations can lead to Omenn syndrome, which is associated with human radiosensitive severe combined immunodeficiency syndrome and alopecia. In this study, we investigated the expression of Ser516 phosphorylation of Artemis in the epidermis and epidermal appendages in normal human scalp skin. Immunofluorescence analysis revealed Ser516 phosphorylation of Artemis in the upper and middle portion of anagen hair follicle [including outer root sheath (ORS), inner root sheath but not stratum basale], hair matrix, sebaceous glands (secretory and ductal portions), eccrine sweat glands (secretory and ductal portions) and epidermis (stratum basale and stratum granulosum), respectively. Artemis phosphorylation at Ser516 was most prominent in ORS keratinocytes. Therefore, we suggest that phosphorylation of Artemis at Ser516 could be involved in regulation of human epidermal appendages.     

Hidradenoma papilliferum of the vulva in association with an anogenital mammary‐like gland

Hidradenoma papilliferum (HP) is a benign adnexal neoplasm which preferentially develops in the anogenital region of women. Although the origin of HP was previously thought to be an apocrine sweat gland, recent studies have suggested that it may derive from the anogenital mammary‐like gland (MLG). In this paper, we present a 43‐year‐old Japanese woman with hidradenoma papilliferum of the vulva. The lesion developed 7 years prior to her visit, and clinically appeared as a skin‐colored cystic nodule. Histopathological examination revealed that the neoplasm was formed by the tubular structures consisting of two types of pleomorphic cells, columnar cells in the luminal layer and cuboidal cells in the basal layer. Further, the surgical specimen contained a wide, divergent, lobular ductal structure located in the vicinity of the neoplastic lesion, which was consistent with MLG.     

A case of ductal sweat gland carcinoma connected to syringocystadenoma papilliferum arising in nevus sebaceus

We report a case of a tumor arising in the preauricular region in a 50-year-old woman. The histopathological findings revealed it to be a ductal sweat gland carcinoma connected to a syringocystadenoma papilliferum (SCAP) arising in a nevus sebaceus. Mucinous stroma, considered to be deposition of hyaluronic acid, was also observed in the ductal carcinoma portion. The immunohistochemical and ultrastructural findings in the ductal carcinoma were compared with those in the SCAP. The proliferating cell nuclear antigen labeling index of the cells in the ductal carcinoma was higher than that of those in the SCAP. Both the ductal sweat gland carcinoma and SCAP showed findings compatible with the ductal segment of a sweat gland.
Ansai S, Koseki S, Hashimoto H, Hozumi Y, Kondo S. A case of ductal sweat gland carcinoma connected to syringocystadenoma papilliferum arising in nevus sebaceus.     

Presence of residual basal cell carcinoma in re-excised specimens is more probable when deep and lateral margins were positive

In order to quantify presence of residual BCC in patients with histologic positive margins after the first excison and to correlate the presence of residual tumor in re‐excised lesions with the location of the positive margin on the first excision, a retrospective evaluation of 2053 surgically treated BCC was performed. Only 38.3% of the re‐excised lesions showed residual tumor. In the group of re‐excised lesions where residual BCC was found, 13% had lateral positive margin in the first excision, 39% had deep positive margin and 48% had both lateral and deep positive margins. In the group of re‐excised lesions where no residual BCC was found, 49% of the primary excised lesions had lateral positive margin, 32% had deep positive margin and 19% had both deep and lateral positive margins. The association between residual tumor and positive margins was statistically significant (p = 0.01). Our findings confirm that presence of residual tumour is more likely when both lateral and deep margins are compromised.     

Langerhans cell histiocytosis associated with breast carcinoma successfully treated with topical imiquimod

Langerhans cell histiocytosis (LCH) encompasses a group of disorders characterized by the proliferation and infiltration of Langerhans cells within internal organs and/or skin. There is often multiorgan involvement; isolated cutaneous LCH is less common. ¹ The aetiology of cutaneous LCH remains uncertain, and debate remains as to whether LCH represents a neoplastic condition or is simply reactive. We report a 53‐year‐old woman who developed isolated cutaneous LCH 15 months after being diagnosed with infiltrating ductal carcinoma of the left breast. The LCH was treated with topical imiquimod, resulting in clinical and histological resolution. Our case highlights the rare association between cutaneous LCH and breast carcinoma, and the clinical and histological response that can be achieved with topical imiquimod. After a diagnosis of LCH, patients require long‐term follow‐up, due to the risk of recurrence and/or development of a subsequent malignancy.     

Primary cutaneous biphasic sarcomatoid basal cell carcinoma with myoepithelial carcinoma differentiation: A new variant

Isolated cases of basal cell carcinoma (BCC) with partial myoepithelial component have been described. However, myoepithelial differentiation has not been described in sarcomatoid basal cell carcinomas, which usually show features resembling osteosarcoma, chondrosarcoma, or leiomyosarcoma. We report a case of an 87‐year‐old man with a forehead lesion that histologically showed a minor component of conventional nodular BCC in transition with a major biphasic sarcomatoid growth composed of invasive spindle‐cell and epithelial‐like components, the latter with a reticular pattern and scattered ductal structures. Both components showed cytological atypia and high mitotic rate (26/10HPF), with atypical mitotic figures. BER‐EP4 immunostaining was exclusively found in the nodular BCC component whereas the sarcomatoid component revealed immunostaining for α‐smooth muscle actin (SMA), muscle‐specific actin (MSA), calponin, and p63 in both epithelial‐like and spindle‐cell populations. Focal immunoreactivity was observed in the epithelial component for S100 and glial fibrillary acidic protein (GFAP). Furthermore, EWSR1‐PBX1 gene fusion was also detected. This is to our knowledge, the first fully documented case of biphasic sarcomatoid BCC with myoepithelial carcinoma differentiation.     

Portable negative‐pressure wound therapy for pyoderma gangrenosum: Report of two cases

Pyoderma gangrenosum is a chronic non‐infectious neutrophilic dermatosis that causes undermining ulcers. Topical therapies for the deep ulcers of pyoderma gangrenosum have not been established. To investigate whether negative‐pressure wound therapy is effective for a pyoderma gangrenosum ulcer, we used the PICO single use negative‐pressure wound therapy system (Smith & Nephew, London, UK) for two pyoderma gangrenosum patients. In these cases, the ulcers decreased in size and necrolytic tissue was removed notably. Moreover, there were no secondary infections nor was there Koebner phenomena. Our cases suggest that portable negative‐pressure wound therapy can be a treatment option for deep, intractable ulcers caused by pyoderma gangrenosum. Because portable negative‐pressure wound therapy devices afford increased mobility to patients, they can give the patient a better quality of life than standard negative‐pressure wound therapy systems do.     

Immunolocalization of aquaporin-5 in normal human skin and hypohidrotic skin diseases

Aquaporin (AQP)‐5 has been shown to be expressed in the secretory parts of mouse, rat and horse sweat glands. However, the precise localization of AQP‐5 in normal and diseased human skin has not been fully determined. The aim of the present study was to further clarify the immunolocalization of AQP‐5 in normal human skin and hypohidrotic skin diseases. Normal human scalp skin and biopsies from skin affected by hypohidrotic diseases were analyzed for AQP‐5 and/or dermcidin expression by immunohistochemistry, immunofluorescence and/or immunoelectronmicroscopy. AQP‐5 was expressed on the apical and basolateral plasma membranes of the clear cells in eccrine sweat coils, but not in ductal components or apocrine glands. Numbers of AQP‐5‐positive coils in the secretory part of eccrine sweat glands were decreased in Sjögren’s syndrome, but not in skin affected by idiopathic segmental anhidrosis or idiopathic pure sudomotor failure. AQP‐5 was mostly localized to the plasma membranes of clear cells in the secretory coils of eccrine sweat glands, suggesting that it plays a role in producing the primary sweat fluid.     

Erbium‐doped yttrium aluminium garnet ablative laser treatment for endogenous ochronosis

Ochronosis is a rare disease characterised clinically by bluish‐grey skin discolouration and histologically by yellow‐brown pigment deposits in the dermis. It occurs in endogenous and exogenous forms. Endogenous ochronosis, also known as alkaptonuria, is an autosomal recessive disease of tyrosine metabolism, resulting in the accumulation and deposition of homogentisic acid in connective tissue. We report a case of facial endogenous ochronosis and coexistent photodamage, which was successfully treated with erbium‐doped yttrium aluminium garnet laser resurfacing and deep focal point treatment to remove areas of residual deep pigment.