Journal of Pathology and Translational Medicine

Case Study

Primary Malignant Melanoma of the Breast: A Report of Two Cases: Jiwon Koh, Jihyeon Lee, So Youn Jung, Han Sung Kang, Tak Yun, Youngmee Kwon; J Pathol Transl Med. 2019;53(2):119-124. Published online November 26, 2018; DOI: https://doi.org/10.4132/jptm.2018.10.18

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Primary malignant melanoma of the breast (PMMB) is a rare tumor with only a few case reports available in the literature. We report two cases of PMMB, one derived from the breast parenchyma and the other from the breast skin. The first case consisted of atypical epithelioid cells without overt melanocytic differentiation like melanin pigments. The tumor cells showed diffuse positivity for S100 protein, tyrosinase, and BRAF V600E. However, the tumor cells were negative for cytokeratin, epithelial membrane antigen, and HMB-45. The second case showed atypical melanocytic proliferation with heavy melanin pigmentation. The tumor cells were positive for S100 protein, HMB-45, tyrosinase, and BRAF V600E. These two cases represent two distinct presentations of PMMB in terms of skin involvement, melanin pigmentation, and HMB-45 positivity. Although PMMB is very rare, the possibility of this entity should be considered in malignant epithelioid neoplasms in the breast parenchyma.

Citations

Citations to this article as recorded by

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Original Article

Alteration of Apoptosis-Related Proteins (Apaf-1, Caspase-9, Bcl-2, p53, and Survivin) According to Malignant Progression in Cutaneous Melanocytic Lesions.: Yeo Ju Kang, Ji Han Jung, Kwnag Il Yim, Kyo Young Lee, Youn Soo Lee, Seok Jin Kang, Chang Suk Kang, Si Yong Kim; Korean J Pathol. 2011;45(3):247-253.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.3.247

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Abstract PDF: BACKGROUND
Apoptosis protease activating factor-1 (Apaf-1), caspase-9, Bcl-2, p53, and survivin are important factors in the pathway of apoptosis, but their clinicopathologic significance remains unclear in human cutaneous melanoma. We investigated the expression of these proteins and their clinical value in human cutaneous melanocytic lesions.
METHODS
We performed an immunohistochemical analysis to examine the expression and distribution of Apaf-1, caspase-9, Bcl-2, p53, and survivin in 36 cases of malignant melanoma (22 cases of primary melanoma and 14 cases of metastatic melanoma) and 41 cases of melanocytic nevus.
RESULTS
The expression of p53 was significantly higher in malignant melanoma than in melanocytic nevus (p<0.01), however the expressions of Apaf-1 and caspase-9 were significantly lower in malignant melanoma compared with melanocytic nevus (p<0.01 and p=0.027, respectively). Also, there was a significant difference for Bcl-2 staining between primary melanomas and metastatic lesions (p=0.004). Nuclear staining for survivin were absent in nevus, but were positive in 14 of 36 melanomas (p<0.01).
CONCLUSIONS
The altered expression of Apaf-1, caspase-9, p53, and survivin are considered to be related to malignant progression in human cutaneous melanocytic lesions. Loss of Bcl-2 can be considered as a prognostic marker of malignant melanomas.

Case Reports

Primary Malignant Melanoma arising in Mucosa of the Palatine Tonsil: A case report.: Ki Jung Yun, Hyang Jeong Jo, Hyung Bae Moon, Sang Won Yoon; Korean J Pathol. 1996;30(1):65-67.

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Abstract PDF: Maligant melanomas of the oral or nasal cavity, and the vulvovaginal area are relatively common among the melanomas of non-ocular mucosa. But, primary malignant melanoma arising in the mucosa of the palatine tonsil is rare. We present a case of primary malignant melanoma arising in the mucosa of the palatine tonsil. A 36-year-old male was admitted for evaluation of a recurrent sore throat. Tonsillectomy was performed on the basis of clinical suspicion of chronic tonsillitis. Grossly, the left tonsil was focally dark. Microscopically, the tonsillar mucosa was diffusely infiltrated with tumor cells. Tumor cells revealed numerous melanin pigments. Intraepithelial nests of tumor cells were noted, but pagetoid spread of tumor cells was not found. Tumor cells were positive for S-100 protein and HMB45 stain. There was no evidence of melanoma in the skin or eye.

Malignant Melanoma of the Anus: Report of a case.: Eun Sun Jung, Byung Kee Kim, Sun Moo Kim, Sang In Shim; Korean J Pathol. 1996;30(3):276-278.

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Abstract PDF: This report describes a primary malignant melanoma which developed in the anus, as documented by light microscopy and immunohistochemistry. A 53-year-old woman had a 4 month history of a protruding mass in the anal canal. The mass was located in the squamo-columnar junction of the anal canal, measuring 5.0x4.5 cm. Its cut surface was dark brown and poorly circumscribed. The histologic appearance was characterized by epithelioid or spindle cells with prominant nucleoli and frequent atypical mitosis. Melanin pigments were strongly seen in Fontana-Masson stain. Immunoreactivity revealed that the cytoplasm of tumor cells was strongly positive with antibody directed against S-100 protein, vimentin and it was focally positive with neuron specific enolase.

Original Articles

Expression of bcl-2 and c-myc Proteins in Epidermal and Melanocytic Tumors.: Young Ha Oh, Chan Kum Park, Jung Dal Lee; Korean J Pathol. 1996;30(9):810-818.

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Abstract PDF: bcl-2 and c-myc protein expression were studied in 44 epidermal (8 seborrheic keratoses, 21 squamous cell carcinomas, and 15 basal cell carcinomas), and 26 melanocytic tumors(8 nevi, and malignant melanomas) by immunohistochemistry using the specific anti-bcl-2 and anti-c-myc monoclonal antibodies. 14 out of 15 basal cell carcinomas(BCC) (93.3%) showed expression of bcl-2 protein, 12 of which (85.7%) showed coexpression of c-myc protein. In the melanocytic tumors, 7 out of 8 nevi showed bcl-2 expression (87.5%). Five of these 7 cases (62.5%) also showed c-myc protein expression. Eight of 18 malignant melanomas(MM) (44.4%) showed expression of bcl-2 protein and 7 of these 8 cases (38.9%) also showed c-myc protein expression. All seborrheic keratoses and squamous cell carcinoma(SCC) were negative for bcl-2 proteins. 12 of 15 SCCs(80%) were positive for c-myc protein. In conclusion, bcl-2 and c-myc proteins were coexpressed in BCCs, nevi, and MMs. Coexpression of bcl-2 and c-myc proteins in these tumors was statistically significant(p<0.01), while no considerable differences of bcl-2 and c-myc expression were found between nevi and MMs. These results suggests that bcl-2 may cooperate with c-myc to promote tumorigenesis of BCCs, nevi, and MMs(p<0.01).

Immunohistochemical Study on the Expression of Mutated p53 Protein and Bcl-2 Protein in Melanocytic Lesions of Skin.: Wha Jin Lee, Joon Hyuk Choi, Won Hee Choi; Korean J Pathol. 1997;31(2):112-120.

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Abstract PDF: To investigate the immunohistochemical expression of mutated p53 protein and bcl-2 protein in the cutaneous melanocytic lesion, 15 cases of compound nevus, 10 cases of congenital melanocytic nevus, 15 cases of primary malignant melanoma(4 cases less than 1.5 mm thick and 11 cases more than 1.5 mm thick), and 10 cases of metastatic malignant melanoma(7 cases in lymph node and 3 cases in soft tissue) were examined. All cases of compound nevi and of congenital melanocytic nevi showed no immunoreactivity for p53 protein. p53 protein overexpression was observed in 75%(3/4) wth primary malignant melanoma less than 1.5 mm thick, 81%(9/11) with primary malignant melanoma more than 1.5 mm thick, and 100%(10/10) with metastatic malignant melanoma. The difference in p53 protein overexpression was statistically significant between benign nevi and malignant melanoma(p<0.01). Bcl-2 protein expression was observed in 73%(11/15) with compound nevus, 70%(7/10) with congenital melanocytic nevus, 75% (3/4) in primary malignant melanoma less than 1.5 mm thick, 54%(6/11) with primary malignant melanoma more than 1.5 mm thick, and 40%(4/10) with metastatic malignant melanoma. These findings suggested that mutation of p53 gene may be an important mechanism in the development of malignant melanoma. Although bcl-2 protein was expressed in cutaneous melanocytic lesion, no correlation was found between p53 protein and bcl-2 protein expression in malignant melanoma.

Clinicopathological Analysis on the 104 Cases of Malignant Melanoma.: Kye Yong Song, Kyeong Cheon Jung, Kwang Hyun Cho, Je Geun Chi, Eui Geun Ham; Korean J Pathol. 1997;31(6):566-573.

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Abstract PDF: The cliniopathological analysis was done on the 104 cases of malignant melanoma diagnosed at the Seoul National University Hospital (SNUH) from 1984 to 1993. The basic clinical data and the pathological items were based on the New Mexico Melanoma Registry Worksheet. The results were as follows. The male to female ratio was 1 : 0.79. Primary cutaneous melanoma was more common in the male (M : F=1 : 0.56) but primary extracutaneous melanoma with slight female dominancy (M : F=1 : 1.25). The peak age was the 6th decade in both cutaneous and extracutaneous malignant melanoma. In 66% (35 cases) of primary cutaneous malignant melanoma, the primary site was located in the acral area (including cases of acral lentiginous and nodular type), of which 63% (41% of total cutaneous melanoma) was acral lentiginous type. Major components of tumor cells were epithelioid. Clark's level of tumor was III or more at the time of the first visit in the majority of the cases (85%). The incidence rate of extracutaneous melanoma was 34.6% (36 cases) among the primary melanoma, and the eyeball (17.3%) was the most prevalent organ. All these features suggest that the racial difference between the Korean and the Caucasian is evident and also that etiologic role of sun damage is not quite marked in the Korean. We also suggest that an early detection program is very important to cure this malignant tumor.

Case Reports

Balloon Cell Malignant Melanoma: A case report.: Ji Young Seo, Soon Young Kim, Jeong Hee Kang, Young Ok Kim, Bang Hur; Korean J Pathol. 1999;33(7):537-539.

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Abstract PDF: Balloon cell malignant melanoma (BCMM) is a rare histologic variant of malignant melanoma, which is composed either predominantly or entirely of large clear or foamy cells. The incidence of balloon cell malignant melanoma is about 0.15% of all cutaneous malignant melanomas. Recently, we experienced a case of cutaneous balloon cell malignant melanoma in the right lower abdomen with right inguinal and both axillary lymph node metastasis in a 56-year-old man. The cutaneous lesion was 4.5 3.5 cm in size, a well-demarcated black nodular mass, involving abdominal skin and subcutaneous tissue. The tumor was histologically composed of two types of tumor cells: predominant clear cell and focal, pigmented spindle cell. The nodal lesion was composed entirely of clear cells. Both clear and spindle cells showed positive reaction for S-100 protein and HMB-45 on immunohistochemistry.

Cytologic Features of Papnicolaou Smears of Malignant Melanoma Arising in Vagina: A Cese Report.: Myung Suk Kang, Bohng Hee Kim, Jae Hoon Park, Youn Wha Kim, Yong Koo Park, Ju Hie Lee, Moon Ho Yang; Korean J Cytopathol. 1995;6(2):209-214.

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Abstract PDF: Primary malignant melanoma of vagina is a rare tumor which is easily misinterpretated in routine cytologic examination. We lately experienced a case of primary malignant melanoma of the vagina with direct cervical extension diagnosed by Pap smear. The cervicovaginal smear showed variable sized clusters of epithelial cells or singly scattered abnormal epithelial cells. Most of the tumor cells had round hyperchromatic nuclei with prominent nucleoli and brownish pigments in cytoplasm. The cytologic findings are compared with histologic features of resected specimen.

Metastatic Melanoma Mimicking a Papillary Carcinoma of the Thyroid in Fine Needle Aspiration Cytology: A Case Report.: Young Ok Hong, Jae Hee Suh, Hee Jeong Cha, Hye Jeong Choi, Young Min Kim; Korean J Cytopathol. 2007;18(2):161-164.

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Abstract PDF: Metastasis to the thyroid gland is very rare in clinical practice. We recently encountered a 65-year-old woman who presented with a large thyroid nodule that mimicked the cytologic features of a papillary thyroid carcinoma on fine needle aspiration biopsy (FNAB). Although initially diagnosed as a papillary thyroid carcinoma, a thorough clinical work-up revealed multiple lesions in the bones, liver, and nasal cavity, which were confirmed as metastases of a malignant melanoma. Despite a thorough physical examination, however, the primary skin lesion could not be identified. Although FNAB shows a high degree of accuracy in diagnosing primary thyroid tumors, it is less accurate in diagnosing metastases to the thyroid gland. A thorough clinical history with appropriate immunohistochemical staining assays is necessary for the accurate diagnosis of metastatic malignant melanoma.

Original Article

Immunohistochemical Evaluation of HMB-45 and S-100 Protein in Melanocytic Tumors.: Chang Soo Park, Hwan Kim, Hyang Mi Ko, Kyung Soo Kim, Ji Shin Lee; Korean J Pathol. 1995;29(2):189-196.

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Abstract PDF: Immunohistochemical staining on paraffin sections for S-100 protein improved diagnostic accuracy for melanocytic tumor. But specificity of S-100 protein in the diagnosis of melanocytic tumor is very low, because S-100 protein was also expressed in neurogenic tumor and salivary gland tumor. To investigate a specific tumor marker for the malignant melanoma, immunohistochemical staining for HMB-45 and S-100 protein was performed on the paraffin sections of 25 cases of malignant melanoma and 46 cases of nevi. Positive reaction for HMB-45 and S-100 protein was diffusely identified in the cytoplasm of tumor cells. Positive ratio for HMB-45 was 100% in malignant melanoma, 92% in junctional component of compound nevus and 0% in intradermal nevus. Positive ratio for S-100 protein was 92% in malignant melanoma, 100% in compound nevus and 100% in intradermal nevus. The sensitivity and specificity for HMB-45 in malignant melanoma were 100%, but those for S-100 protein were 92% in sensitivity and 86.7% in specificity. These results indicate that HMB-45 has a high sensitivity and specificity for malignant melanoma cells and it can be quite useful for the histopathological diagnosis of malignant melanoma.

Case Report

Malignant Melanoma Arising in Giant Congenital Melanocytic Nevus: A case report.: Jung Sun Kim, Sang Yong Song, Kye Yong Song, Je G Chi; Korean J Pathol. 1993;27(6):650-655.

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Abstract PDF: Giant congenital melanocytic nevus is found in 0.1% of live born infants. If present, this lesion has a 6.3% chance to develop malignant melanoma. We report such a case in a 22-year-old woman who had multiple pigmented skin lesions since birth. Rapidly growing masses were recently detected in the 19 cm-sized occipital pigmented lesion. Removed scalp lesion revealed yellowish white lobulated soft nodules in the background of pigmented nevus. Microscopically, the nodules consisted of epithelioid cells with prominent nucleoli, and pleomorphic cells including signetring cells. These cells seldom contained melanin pigment. There were metastatic aggregates of tumor cells in the cervical lymph node, which were reminiscent of germinal centers of lymph nodes. S-100 protein immunostaining was helpful to distinguish them. Incidentally, focally scattered pigmented spindle cells were seen in the capsule of a lymph node

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