Motoki Kurokawa

CD56: a useful marker for diagnosing Merkel cell carcinoma

BACKGROUND Merkel cell carcinoma (MCC) of the skin is an aggressive but rare malignant neuroendocrine tumor. For its pathological diagnosis, we use a panel of immunohistochemical markers, such as cytokeratin 20 (CK 20), epithelial membrane antigen (EMA), chromogranin A, neuron specific enolase (NSE), synaptophysin, and Leu7 (CD57) to demonstrate its epithelial and neuroendocrine features. CD56, or neural cell adhesion molecule (NCAM), has been demonstrated recently as the tumor marker of the pulmonary neuroendocrine cell system. Its expression in MCC, however, has still rarely been investigated. Furthermore, in such very few previous studies on NCAM expression in MCC, all the tumor cells were not necessarily demonstrated to express NCAM. OBJECTIVES To study the immunoreactivity of CD56 in MCC, especially using a monoclonal antibody of a clone 1B6, different from those adopted in the previous reports. METHODS We reexamined CD56 expression immunohistochemically in five MCC cases, along with the conventional panel of markers described above, using paraffin-embedded tissue sections. RESULTS CD56 revealed the most diffuse and intense positive staining, which was noted along the cell borders, in all specimens compared with other neuroendocrine tumor markers. CONCLUSIONS The results of our study indicate that CD56, especially a new monoclonal antibody (clone 1B6), is a useful immunohistochemical marker for MCC.

New entity, definition and diagnostic criteria of cutaneous adult T-cell leukemia/lymphoma : Human T-lymphotropic virus type 1 proviral DNA load can distinguish between cutaneous and smoldering types

Adult T‐cell leukemia/lymphoma (ATLL) has been divided into four subtypes up to now: (i) acute; (ii) lymphoma; (iii) chronic; and (iv) smoldering. Skin lesion(s) may be present and the cases showing less than 5% abnormal T‐lymphocytes in peripheral blood without involvement of other organs, have been classified as smoldering ATLL. However, this type of ATLL with skin manifestations had a worse prognosis than that without skin lesions. This study aimed to define and distinguish cutaneous ATLL lacking nodal lymphoma and leukemic change from smoldering ATLL. We propose an entity of cutaneous ATLL, which has less than 5% abnormal T lymphocyte in peripheral blood, a normal lymphocyte count (i.e. <4 × 109/L), no hypercalcemia and lactate dehydrogenase values of up to 1.5 times the normal upper limit. At least one of the histologically proven skin lesions should be present accompanying monoclonal integration of human T‐cell lymphotropic virus type 1 (HTLV‐1) proviral DNA in the skin lesion. Blood samples were collected from 41 HTLV‐1‐infected patients, 21 asymptomatic carriers, 16 patients with cutaneous ATLL and four patients with smoldering ATLL. HTLV‐1 proviral loads, soluble interleukin‐2 receptors and other parameters were examined in each case. HTLV‐1 proviral DNA loads in smoldering ATLL group are significantly higher than those in asymptomatic carrier and cutaneous ATLL group. Cutaneous ATLL may be a distinct entity that should be separated from smoldering ATLL clinically and virologically.

Analysis of hepatitis C virus (HCV) RNA in the lesions of lichen planus in patients with chronic hepatitis C: detection of anti-genomic- as well as genomic-strand HCV RNAs in lichen planus lesions.

BACKGROUND Hepatitis C virus (HCV) is a single-strand RNA virus. The association of lichen planus with chronic HCV infection has been reported, as has been cryoglobulinemic purpura, psoriasis, urticaria, and porphyria cutanea tarda. However, the cause of lichen planus is unclear. OBJECTIVES To investigate whether genomic- and/or anti-genomic-strand HCV RNAs are present in the lichen planus lesions of chronic hepatitis C patients and to elucidate the pathogenesis of lichen planus. METHODS Reverse transcription-polymerase chain reaction (RT-PCR) followed by nested-PCR was carried out to detect HCV RNA using RNA samples from lichen planus lesions of three patients with chronic hepatitis C. Since it is well known that commonly there is relatively dense inflammatory cell infiltration mainly in the upper dermis in lichen planus, the same RT-PCR procedure was performed using RNA from peripheral blood leukocytes from the same patients. In addition, in one patient, the same procedure was also performed using an RNA sample from normal skin. RESULTS Bands of the appropriate size (161 base pairs corresponding to region 98-258 of HCV RNA) in the nested-PCR products for both genomic- and anti-genomic-strands were detected in lichen planus lesions as well as in peripheral blood leukocytes in all the cases. CONCLUSION To the best of our knowledge, this is the first report showing the presence of anti-genomic- as well as genomic-strand HCV RNAs in lichen planus lesions in patients with chronic hepatitis C; suggesting that HCV-associated lichen planus lesions may be sites of HCV replication.

Three Cases of Malignant Melanoma Arising on Burn Scars

It is well known that up to 2% of chronic burn scar lesions can transform into malignant tumors. Most of them are squamous cell carcinoma (SCC) and, more occasionally, basal cell carcinoma (BCC). The incidence of malignant melanoma (MM) is extremely low. To the best of our knowledge, there are only 23 such cases reported in the literature. We report here three cases of MM arising on burn scars and analyze the 23 cases reported previously. Case 1: A 74‐year‐old Japanese man sustained a burn injury on about 54% of his whole body surface when he was accidentally bathed in boiling oil at the age of 37 years old. Some small tumors developed on the burn scar on his right lumbar region. A wide excision of the tumor was performed. Case 2: A 51‐year‐old Japanese woman was injured on her right forearm and face by deep burns from a flame when she was 7 months old. She presented with a rapidly growing, painless black nodule on the dark skin lesion on her right forearm. She was treated with a wide excision followed by a full‐thickness skin graft. Intravenous administration of one unit of OK‐432 every week has been continued. Case 3: A 73‐year‐old Japanese woman was burned on her left leg and hand from a flame when she was 6 years old. A nodular lesion appeared within the ulcer two months previously and it was growing rapidly. This lesion was ulcerated on the top of its central area and was slightly reddish without any pigmentation. The patient was treated with a wide excision and a split‐thickness skin graft. The 5‐year survival rate of MM in an old burn scar is 53.6%. It is suggested that the prognosis of burn scar carcinoma is not worse than that of non‐burn scar carcinoma.

Bilateral lichen striatus.

We describe a very rare case of bilateral lichen striatus on the lower extremities with a history of more than ten years. Histopathologically, the lesions demonstrated a lichenoid tissue reaction with foci of spongiosis and perivascular inflammatory cell infiltration. In addition, the finding of lymphocytic infiltrations around the eccrine duct was observed. They were treated successfully with topical application of corticosteroid ointment. To the best of our knowledge, no other lichen striatus case has been reported with bilateral distribution and such long‐term persistence.

A case of pemphigus vulgaris accompanied by multiple myeloma

Pemphigus is a mucocutaneous intraepithelial blistering disease caused by autoantibodies to epithelial cell adhesion molecules (desmoglein). The association between pemphigus and malignant neoplasm is well recognized. We present the case of a 62‐year‐old woman with pemphigus vulgaris accompanied by multiple myeloma. To the best of our knowledge, this is the first report of a case of pemphigus vulgaris concomitant with multiple myeloma. From the results of immunoblotting using normal human epidermal extracts and indirect immunofluorescence using rat bladder sections, and her clinical manifestations, our case does not seem to be one of paraneoplastic pemphigus.

Reappraisal of the expression of mast cell proteases of Mongolian gerbils (Meriones unguiculatus)

Mast cell proteases in the tongue and jejunum of Mongolian gerbils (Meriones unguiculatus) were examined by enzyme‐histochemical methods. Both trypsin‐like (tryptase) and chymotrypsin‐like (chymase) protease activities were demonstrated in mast cells in the tongue of fresh cryosections. When frozen sections of the tongue were post‐fixed in various fixatives, those fixed in Carnoys fluid showed strongest enzyme activities. Tryptase and chymase activities in paraffin sections of both tissues were well preserved when tissues were fixed in Carnoys fluid at 4°C for 15 min. However, enzyme activities in both tissues, especially in the tongue, were drastically reduced by longer fixation time and higher temperature. When Carnoy‐fixed (4°C for 15 min) paraffin sections were treated with heparinase I or chondroitinase ABC before enzyme‐histochemical stainings for proteases, tryptase activities were lost entirely in the tongue and mostly in the jejunum by heparinase I digestion, and slightly in both organs by chondroitinase ABC digestion. In contrast, chymase activities at both sites were not influenced by these pretreatments. These results show that although mast cells in the tongue as well as in the jejunum of Mongolian gerbils contain both tryptase and chymase activities, their stability to fixations is variable among organs so that tissue fixation conditions are crucial for the preservation. At least some part of the stability of mast cell proteases is dependent on the proteoglycans present in mast cell granules.

Two Cases of Angiosarcoma of the Face

Angiosarcoma is a rare vascular malignant tumor most commonly seen on the scalp of elderly people. We report here two cases of angiosarcoma of the face in 74‐ and 75‐year‐old males. It is very unusual to find the development of an angiosarcoma with a rosacea on the face. To the best of our knowledge, only three such cases have been reported.