Takashi Anan

Paraneoplastic pemphigus associated with corneal perforation and cutaneous alternariosis: A case report and review of cases treated with rituximab

Hisashi KOKUBA, Masakazu TAKAHARA, Bungo OHYAMA, Takashi HASHIMOTO, Masutaka FURUE Department of Dermatology, Hiroshima Red Cross Hospital, Atomic-bomb Survivors Hospital, Hiroshima, Department of Dermatology, Kyushu Central Hospital, Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, and Department of Dermatology, Kurume University School of Medicine, Fukuoka, Japan

Erythema Nodosum and Granulomatous Lesions Preceding Acute Myelomonocytic Leukemia

A 65‐year‐old female with a one‐month history of painful eruptions on her lower extremities was admitted to our hospital. Histological examination revealed erythema nodosum (EN), and the patient was treated with oral prednisolone (PSL; 20 mg daily). The eruptions subsided in two weeks. One month later, painful reddish eruptions recurred on her upper limbs and abdomen in addition to her lower extremities. A skin biopsy from an abdominal erythematous plaque revealed a non‐caseating granuloma without microorganisms or foreign‐body materials. These eruptions also disappeared with treatment with oral PSL (20 mg daily). No underlying disease, including sarcoidosis, diabetes mellitus, or rheumatoid arthritis, was found. However, five months later, the patient developed conspicuous leukocytosis. She was diagnosed with acute myelomonocytic leukemia (M4) and treated with chemotherapy. After complete remission had been achieved, the EN reappeared, in association with an increase in blastic cells in the bone marrow. Serum levels of tumor necrosis factor‐alpha and interleukin‐1 beta, which are thought to be essential for granuloma formation and induction of EN, were markedly elevated. Physicians must remember that recurrent EN and granulomatous lesions can be a prodromal sign of leukemia.

Histopathological diagnosis of epithelial crateriform tumors: Keratoacanthoma and other epithelial crateriform tumors.

Keratoacanthoma (KA) is a unique and distinct clinicopathological entity, although there is often confusion regarding its differentiation from other types of crateriform tumors. In this study, the clinicopathological features of 380 epidermal crateriform tumors with a central keratin plug were re‐examined and the tumors were histologically classified into seven types: (i) crateriform verruca; (ii) crateriform seborrheic keratosis; (iii) KA; (iv) KA with a conventional squamous cell carcinoma (SCC) component (KA‐like SCC and KA with malignant transformation); (v) crateriform Bowens disease; (vi) crateriform SCC arising from solar keratosis; and (vii) crater form of infundibular SCC. Our study proved that incidence of SCC developing in KA lesions was 17.4%. The incidence rate differed depending on a patients ages: 8.3% in patients less than 70 years of age and 24.3% in those aged 70 years and older. Nearly all of the malignant crateriform neoplasms (94.7%) occurred on sun‐exposed areas. Lesions on the face included 138 KA (59.5%), 65 malignant crateriform neoplasms (28%) and 29 benign crateriform neoplasms (12.5%). We conclude that KA is not a variant of SCC, but a benign and frequently regressing proliferative lesion or borderline neoplasm, although there is the potential for SCC to arise within KA. Because the incidence of SCC developed in KA lesions and the incidence of other malignant crateriform neoplasms are higher in patients aged 70 years and older, KA‐like lesions on sun‐exposed areas over 70 should be assessed carefully in consideration of the potential risk of malignancy.

CD117 (KIT) is a useful immunohistochemical marker for differentiating porocarcinoma from squamous cell carcinoma

Distinguishing porocarcinoma from squamous cell carcinoma (SCC) is clinically significant but can pose a diagnostic dilemma. The present study sought to confirm the diagnostic utility of CD117 immunohistochemistry in distinguishing porocarcinoma from SCC and to examine histologic, carcinoembryonic antigen (CEA) immunohistochemical and CA19‐9 immunohistochemical differences between these tumors.

Clinicopathological study of crateriform verruca: Crateriform epithelial lesions histopathologically distinct from keratoacanthoma.

Keratoacanthoma (KA) is a distinct clinicopathological entity, but it is often confused with other crateriform tumors. This study re‐examined the clinicopathological features of 380 crateriform epithelial tumors with a central keratin plug. Seventy‐six tumors (20%) had histopathological features that differed from solitary KA and were more verruca‐like, and we designated these lesions as crateriform verruca (CFV). We performed clinicopathological re‐examination of these neoplasms with a crateriform architecture and epithelial lip‐like structures similar to KA, which also displayed histopathological features reminiscent of verruca vulgaris, such as finger‐like exophytic projections with hyperkeratosis and acanthosis, focal hypergranulosis and arborization. Clinical data on CFV were also summarized. The main histopathological differences from KA were that CFV showed proliferation of keratinocytes with a similar size and regular arrangement, and the base of CFV was well demarcated without endophytic growth. Interestingly, some CFV were partly composed of epithelial cells with large pink cytoplasm in the upper malpighian layer between papillomatous projections. Furthermore, areas of trichilemmal‐like keratinization without formation of the granular layer were seen in some lesions. These types of CFV were hardly distinguishable from KA, unless it is recognized that CFV may contain trichilemmal keratinization‐like areas accompanied by large epithelial cells with eosinophilic cytoplasm. We have proposed the term CFV for these verrucous neoplasms to differentiate them from KA.

Maintenance of long-term remission using oral administration of low-dose etoposide in a patient demonstrating a relapse of blastic natural killer-cell lymphoma

Cutaneous manifestations are frequent in cases of blastic natural killer (NK)-cell lymphoma, which is a rare malignant lymphoma. Blastic NK-cell lymphoma has a poor prognosis, with repeated relapses, and most patients with this disease are elderly. It is therefore important to develop treatments that prevent relapse of this lymphoma without severe adverse effects, so that the quality of life of patients with this disease can be maintained. We report here a case of blastic NK-cell lymphoma with relatively long-term survival, in which the oral administration of low-dose etoposide seemed to be useful for preventing relapse of the disease. A 72-year-old man presented with a tumour on the flexural region of his right forearm and multiple erythematous plaques on his back in December 2001. He had first become aware of a small tumour on his right forearm about 6 months earlier, and the tumour had been gradually increasing in size since then. He also noted multiple eruptions on his back early in December 2001. On examination, the dome-shaped tumour on the patient’s right forearm measured 52 · 46 · 7 mm. The tumour was purplish-red and rather hard with slight elasticity (Fig. 1a). The multiple erythematous plaques on his back were either bright or dark-red in colour (Fig. 1b). There was no lymphadenopathy. A biopsied specimen of the tumour on the right forearm revealed diffuse, dense infiltration and a proliferation of medium-sized pleomorphic lymphocytic cells throughout the entire dermis, although a Grenz zone was observed beneath the epidermis. The infiltrating lymphocytic cells had atypical features and some mitotic cells were also found (Fig. 2a). Immunohistochemical and in situ hybridization analysis of the biopsied material revealed that the infiltrating atypical cells were positive for CD4, CD43, CD56 (Fig. 2b) and terminal deoxynucleotidyl transferase, and negative for CD3, CD7, CD8, CD16, CD20, CD33, CD34, CD57, CD68, CD79a, myeloperoxidase and Epstein– Barr virus-encoded small RNA (Fig. 2c). No rearrangement of either the gene for T-cell receptor (TCR)-b or the gene for TCR-c was detected by Southern-blot analysis.

Clinicopathological analysis of 384 cases of poroid neoplasms including 98 cases of apocrine type cases

We examined 384 cases of poroid neoplasms. Most cases (n = 279, 72.7%) exhibited the features of only one subtype. One hundred and ninety‐eight cases (51.6%) showed only the features of poroma (P), 20 (5.2%) hidroacanthoma simplex (HS), five (1.3%) dermal duct tumor (D) and 56 (14.6%) hidradenoma (HA). Composite tumors of those four subtypes were observed in 105 cases (27.3%). In the trunk and lower extremities, lesions with the features of P were observed at higher rates than other sites. Those of HS and D were more frequently observed in the lower extremities. Those of HA were seen at higher rates in the scalp, face, neck and genitalia. Ninety‐eight cases (25.5%) showed decapitation secretion and diagnosed as apocrine type lesion. Apocrine type lesions were frequently observed in the lesions on the genitalia (40.0%), scalp (31.8%) and trunk (31.1%), whereas at lower rates in those on the neck (21.4%) and lower extremities (24.0%). In apocrine type cases, the lesions were located more frequently on the scalp and trunk than non‐apocrine type, whereas were less frequent on extremities. The rate of apocrine type lesions in the cases with only one subtype (19.7%) was lower than that of those with composite tumors (41.0%). In the apocrine type (43.9%), composite tumors are more frequent than in the non‐apocrine type (21.7%). In D (40.8%) and HA (32.3%), apocrine type lesions were more frequently observed than other subtypes. In conclusion, it should be noted that a quarter of poroid neoplasms are composite tumors and/or show apocrine differentiation.

Skin Cancer Screening on a Fishing Island and in an Inland Agricultural Area of Japan

We performed skin cancer screening from 2000 to 2004 at two locations in Japans Oita Prefecture: Himeshima, a small fishing island, and Naoiri, an inland agricultural area. We found 108 and 21 cases of AK in Himeshima and Naoiri, respectively. None of the AKs transformed into SCC, and 21.7% of the AKs underwent spontaneous remission during our observation period. The prevalence and incidence of AK in Himeshima were five times higher than in Naoiri: 1,399 and 826 per 100,000 population, respectively, in the fishing village, vs. 261 and 164 in the agricultural community. Seven and three cases of BCC were observed in Himeshima and Naoiri, respectively. There were two cases of SCC in Himeshima. The highest risk ratio of skin types I to III was 9.2 in Himeshima. Although people engaged in outdoor occupations are thought to be more prone to skin cancer and precancerous skin lesions, our results suggested different potentials for AK in people engaged in different outdoor occupations.

Low-grade Neuroendocrine Carcinoma of the Skin (primary Cutaneous Carcinoid Tumor) as a Distinctive Entity of Cutaneous Neuroendocrine Tumors: A Clinicopathologic Study of 3 Cases With Literature Review.

Abstract: There is scarcity of information on primary cutaneous low-grade neoplasms commonly known as carcinoid tumors, owing to their rarity. The authors present 3 cases that were named “low-grade neuroendocrine carcinoma of the skin” (LGNECS). These occurred in the dermis and subcutis of the anterior chest or the inguinal region in the elderly. Histologically, the tumors showed infiltrating proliferation of nests of various sizes, with low-grade neuroendocrine cytologic features but without mucin production. All cases exhibited varying degrees of intraductal tumor components. On immunohistochemical examination, these tumors expressed estrogen receptor alpha, progesterone receptor, androgen receptor, gross cystic disease fluid protein 15, mammaglobin, and GATA3 as well as neuroendocrine markers. Although a literature review revealed 8 additional possible cases with no evidence of other diseases, it was difficult to determine if these were true cases of LGNECS, because of the limited information available. Based on its characteristic histologic features and immunoprofile, it can be proposed designating LGNECS as a distinct entity among cutaneous neuroendocrine tumors. Otherwise, such tumors could be misdiagnosed as mammary carcinomas (particularly when involving the skin of the breast) or as metastatic visceral neuroendocrine tumors of the skin.

Tubulopapillary Cystic Adenoma With Apocrine Differentiation: A Unifying Concept for Syringocystadenoma Papilliferum, Apocrine Gland Cyst, and Tubular Papillary Adenoma

Abstract: Syringocystadenoma papilliferum (SCAP), apocrine gland cyst (AGC, also called apocrine hidrocystoma or apocrine cystadenoma), and tubular papillary adenoma (TPA) with apocrine differentiation are defined as proliferations of apocrine epithelium with myoepithelial cells. At Sapporo Dermatopathology Institute, we retrieved 308 benign neoplastic lesions diagnosed as SCAP, AGC, or TPA and combinations of these entities. Among the 308 lesions, 202 (66%) exhibited features of only one type, of which 144 (47%) were AGC, 39 (13%) were TPA, and 19 (6%) were SCAP. The other 106 lesions (34%) had features of 2 or more types, including 56 lesions that were AGC + TPA (18%), 2 that were AGC + SCAP (1%), 34 that were TPA + SCAP (11%), and 14 that were AGC + TPA + SCAP (5%). The most frequent site of these lesions was the face (56%), followed by the scalp (13%). Lesions with the features of AGC were more frequently found on the face, especially the periocular region, than at other sites. TPA lesions were more frequent on the face and scalp than at other sites, whereas SCAP lesions were preferentially found on the face, scalp, and trunk. We also retrieved clinicopathological data and other information. We propose a unifying concept for AGC, TPA, and SCAP. Approximately one-third of these lesions are composite entities with the features of 2 or 3 different tumors, and we propose calling such tumors tubulopapillary cystic adenoma with apocrine differentiation.