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Background
Malignant melanomas have been described in nearly every organ besides the skin. The prognosis depends upon the site and extent of the local disease. Histologically, these melanomas show identical histologies to more conventional melanomas of the skin.
OUTLINE
Gross Appearance and Clinical Variants Anorectal
Gastrointestinal
Genitourinary
Leptomeningeal
Mediastinum
Mucosal
Neurocutaneous melanosis
Ocular
Oral
Ovary
Sinonasal
Thymus
Urethra
Vagina
VulvaCommonly Used Terms Internet Links
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION GENERAL VARIANTS ANORECTAL MELANOMA Dis Colon Rectum 1995;38:146
Third most common site after skin and eye
Mean age 60-72 years
5 YRS of 9-17%Higher incidence in Southwestern Native Americans and Northern Pakistani with relative incidences of 11% and 14.2%
Present with bleeding, pain, and a tumor mass
32.5-37% present with localized disease
28-41% present with regional lymph node involvementAIDS patients have a higher incidence
Surgical resection is treatment
Poor response to radiotherapy and chemotherapy
Am J Clin Pathol. 2006 Jul;126(1):93-100. Abstract quote
We reviewed 17 cases of primary anorectal malignant melanoma. Morphologic features evaluated included junctional change, pigmentation, morphology, and mitotic rate. Immunohistochemical stains were performed for/with S-100 protein, HMB-45, MelanA, tyrosinase, vimentin, KIT, and pankeratin. Morphologic subtypes were as follows: epithelioid, 12 cases; spindle cell, 7 cases; lymphoma-like, 10 cases; and pleomorphic, 6 cases. Pigmentation was present in 9 cases.
Junctional change was present in 6 cases. The mitotic rate was 3 or more per high-power field in 8 cases. S-100 protein was present in all cases, HMB-45 stained 16 of 17, MelanA was present in 14 of 15, tyrosinase in 12 of 14, vimentin in 13 of 14, and KIT in 12 of 16. Pankeratin was absent in all cases. The mean length of follow-up was 25.6 months (range, 8-96 months), and the average survival with disease was 32.3 months (range, 8-96). No morphologic or immunohistochemical features were predictive of survival. Anorectal malignant melanoma shows considerable morphologic variability.
Immunohistochemical staining is similar to cutaneous melanomas. Expression of KIT was present frequently, including cases with spindle cell morphologic features, in which it may lead to confusion with gastrointestinal stromal tumors.
Anorectal melanoma: clinical features, recurrence and patient survival.
Abbas JS, Karakousis CP, Holyoke ED.
Int Surg 1980 Sep-Oct;65(5):423-6 Abstract quote
In this study, 20 cases of anorectal melanoma seen over a 50-year period were analyzed. It is common to mistake this tumor for other benign conditions because of its similar clinical presentation and the frequent absence of pigmentation.
Patients with anal lesions had a significantly longer mean survival than those with rectal lesions. Abdominoperineal resection provided patients with a significantly longer survival than did local excision. In spite of radical surgery, recurrence rates were high and were mainly local, hepatic or disseminated. Earlier diagnosis and improved adjuvant treatment may lengthen survival.
Anorectal malignant melanoma. A clinicopathologic study, including immunohistochemistry and DNA flow cytometry.
Ben-Izhak O, Levy R, Weill S, Groisman G, Cohen H, Stajerman S, Misselevich I, Nitecky S, Eidelman S, Kerner H.
Department of Pathology, Rambam Medical Center, Haifa, Israel.
Cancer 1997 Jan 1;79(1):18-25 Abstract quote
BACKGROUND: Anorectal malignant melanoma is a rare tumor with an extremely poor prognosis. DNA flow cytometric study as well as detailed immunohistochemical study have not been reported previously.
METHODS: Eighteen cases of anorectal melanoma were studied, including immunohistology for melanoma markers and epithelial markers and DNA flow cytometric study of paraffin blocks.
RESULTS: Most patients were Ashkenazi Jews, compared with Sephardi Jews and Arabs. Of the 17 patients followed, 14 died of disease at 4-39 months from presentation. Three patients were alive with disease at 12, 53, and 72 months of follow-up. Tumor thickness ranged from 3-35 mm (mean, 12.8 mm). The 2 long term survivors had tumor thickness < or = 7 mm. No correlation was found between the mode of primary surgical treatment (8 patients: abdominoperineal resection; 10 patients: local excision) and outcome. Vimentin, HMB-45, and S-100 protein stainings were positive in 18, 17, and 15 tumors, respectively. Polyclonal carcinoembryonic antigen (CEA), broad-spectrum cytokeratin, epithelial membrane antigen, monoclonal CEA, and TAG-72 (B72.3) stainings were positive in 13, 3 (only focal and rare staining), 2, 0, and 0 tumors, respectively. Thirteen tumors had adequate material for DNA analysis, and all were DNA aneuploid. S-phase fraction could be assessed in 11 tumors and ranged from 7.7-24% (mean, 14%). An S-phase fraction of < 10% was observed in the 2 long term survivors.
CONCLUSIONS: Anorectal melanoma in this study carried a grave prognosis. The frequent staining for polyclonal CEA (with negative monoclonal CEA staining) was probably due to nonspecific cross-reacting antigens. The occasional staining for epithelial markers warrants a comprehensive immunohistochemical study to ensure a correct diagnosis, especially in small biopsies of amelanotic undifferentiated tumors that lack junctional changes. The aneuploidy of all tested tumors reflected their highly malignant behavior. A trend toward longer survival was observed in patients with thin tumors and an S-phase fraction of < 10%. However, due to the small number of survivors, the latter observation should be further tested in a larger scale series.
Primary anorectal melanomas: an istitutional experience.
Rossetti C, Koukouras D, Eboli M, Andreola S, Bertario L.
Dept. of Surgical Oncology A, Istituto Nazionale Tumori, Milan, Italy.
J Exp Clin Cancer Res 1997 Mar;16(1):81-5 Abstract quote
Primary melanomas (M) of the rectum and anal canal are a rare pathological event, constituting approximately 1% of all invasive tumors in this site.
From January 1973 to December 1990 at the Istituto Nazionale per lo Studio e 1a Cura dei Tumori of Milan, 11 patients were treated for M (5 males and 6 females), with a mean age of 60 years (range 40-80). The site of origin of the M was rectal in four patients, anal in five patients and in the anorectal joint in two patients. The lesion was prevalently polypoid and the average size was 4 cm (1-7.5 cm). Symptoms referred by the patients were rectal bleeding and tenesmus. In one patient the diagnosis was made after biopsy of an inguinal metastatic lymphnode. Of the 11 patients, six underwent curative resection (four Miles' resections and two local excisions). One patient is still alive with no evidence of disease after 120 months. The remaining five patients were submitted to palliative treatment, due to the presence of metastases in four of them and to age and general conditions in one. All of these patients died at 1, 2, 4, 5, and 6 months (median: 4 months). Overall median survival was eight months: 20 months in the radically treated group and four months in the palliatively treated group.
Our data are in agreement with those reported in literature and confirm the prognostic severity of anorectal M due both to late diagnosis and the biological aggressiveness of the neoplasm.
GASTROINTESTINAL Most tumors are metastastic
Primary tumors are very rare
5YRS of 2.2-5.7%GENITOURINARY TRACT FEMALE Cancer 1993;7:1893
Mean age of 58-67.7 years
Incidence of 1.08/million for vulva
Incidence of 0.26/million for vagina5YRS for vulva is 21.7%-54%
5YRS for vagina is 10-19%
Vulvar Malignant Melanoma Associated With Human Papillomavirus DNA: Report of Two Cases and Review of Literature
Angela Rohwedder, Ph.D.; Brooke Philips; John Malfetano, M.D.; Daniel Kredentser, M.D.; J. Andrew Carlson, M.D.
Am J Dermatopathol 2002; 24(3):230-240 Abstract quote
Oncogenic human papillomavirus (HPV) types such as HPV 16 are known to play a crucial role in the development of anogenital carcinomas. The etiology of anogenital malignant melanoma is unknown.We report two case of vulvar malignant melanoma in which multiple HPV types including HPV 16 and putative novel HPV types (alb-1, alb-2, alb-7, and alb-10) were identified by degenerated nested polymerase chain techniques (polymerase chain reaction) in both the malignant melanoma and surrounding skin. One melanoma was associated with lichen sclerosus, and the other, with melanoma in situ and pigmented vulvar squamous papillomatosis.
These melanomas harbored HPV types alb-7, and HPV 16 as well as alb-1, respectively. HPV types 16, 20, 21, 36, alb-2, and AJ001060 were detected in vulvar skin affected by lichen sclerosus. Vulvar squamous papillomatosis harbored HPV types 28 and alb-10. HPV 16 was physically integrated into the host genome in lichen sclerosus skin and possibly in the melanoma associated with pigmented vulvar squamous papillomatosis. Twenty-two percent (4 of 18) of normal control specimens from skin tumor excisions were found to harbor HPV DNA (HPV types 3, 54, and alb-7); none of these control samples harbored multiple HPV DNA. These findings of multiple HPV DNA and integrated HPV 16 in skin associated with vulvar malignant melanoma indicate that HPV may play a role in the development of vulvar malignant melanoma.
The role of HPV could be either direct through infection of melanocytes or indirect as a cofactor with free radicals in chronic fibroinflammatory vulvar disorders such as lichen sclerosus.
GENITOURINARY TRACT MALE J Urol 1984;132:123
Penile to urethral ratio 2.4:1
Glans penis and distal urethra most common sites
Average age 63-64 years
5 YRS of 23%HEAD AND NECK Arch Otolaryngol Head Neck Surg 1996;122:985
0.5-2% of all malignant melanomas
Clinically more aggressive than cutaneous counterpart with 5 year survival of 10-38%
Sessile or polypoid and frequently ulceratedOral melanoma is relatively common in Japan accounting for 7.5% of all melanomas
Clinicopathologic differences in malignant melanoma arising in oral squamous and sinonasal respiratory mucosa of the upper aerodigestive tract.Prasad ML, Busam KJ, Patel SG, Hoshaw-Woodard S, Shah JP, Huvos AG.
Department of Pathology, Ohio State University Medical Center, Columbus 43210, USA.
Arch Pathol Lab Med. 2003 Aug;127(8):997-1002. Abstract quote OBJECTIVE: Primary mucosal melanomas are rare tumors. We compare melanomas arising in 2 histologically different mucosa, the stratified oral squamous mucosa and pseudostratified sinonasal respiratory mucosa, to investigate the clinicopathologic influence of native mucosal histology on the tumor.
METHODS: Clinicopathologic features of 36 melanomas arising in the squamous mucosa of the oral cavity were compared with 59 melanomas arising in the sinonasal respiratory mucosa.
RESULTS: The median age of patients was 61 and 63 years for oral and sinonasal melanomas, respectively, with the squamous and respiratory mucosa covering the maxilla being most frequently involved (68.7% and 66%, respectively). The former had a remarkable male predilection (28 men, 8 women), while the latter affected both sexes equally (29 men, 30 women). The oral melanomas were more likely to be detected in the early in situ or microinvasive stage (4 cases vs none, P =.008) and were more frequently amelanotic (14 vs 12, P =.049) than sinonasal melanomas. The sinonasal melanomas were frequently thicker (median thickness, 9 vs 2.6 mm), polypoid (29 vs none), ulcerated (57 vs 20), and necrotic (57 vs 14) than oral melanoma (P <.001). Pseudopapillary architecture was more frequent in sinonasal melanomas (16 tumors vs none, P <.001), and desmoplastic melanomas were more frequent in the oral mucosa (6 vs 1, P =.005). Sinonasal melanoma showed vascular and deep tissue invasion more frequently than oral melanoma; however, no significant difference in disease-specific survival was noted (median survival, 2.8 years vs 3.0 years; 5-year survival, 37% vs 35%, respectively).
CONCLUSION: Sinonasal melanomas demonstrated aggressive morphologic features significantly more frequently than oral melanomas; however, prognosis remained similar in both groups.
Prognostic factors for malignant melanoma of the squamous mucosa of the head and neck.Prasad ML, Patel S, Hoshaw-Woodard S, Escrig M, Shah JP, Huvos AG, Busam KJ.
Departments of Pathology (M.L.P., A.G.H., K.J.B.) and Surgery (S.P., M.E., J.P.S.), Memorial Sloan-Kettering Cancer Center, New York, New York, and the Department of Pathology.
Am J Surg Pathol 2002 Jul;26(7):883-92 Abstract quote Primary malignant melanomas of the squamous mucosa of the head and neck are rare. To learn more about the prognostic significance of various histologic parameters we examined the pathologic features of squamous mucosa from 40 patients seen at a single institution and correlated them with clinical outcome.
Follow-up information was available on 37 patients. Thirty-five were treated with surgical resection and two were treated with radiotherapy. Twenty-six were dead at follow-up. Twenty-one of them died of disease. The interval between diagnosis and death ranged from 1 month to 16.5 years (median survival, 2.4 years). Eleven patients were alive at 4 months to 19.5 years after the diagnosis: six of them with disease and five of them free of disease (mean follow-up, 3.5 years). Predictors of poor survival by univariate analysis were the presence of vascular invasion (overall survival, p = 0.007; disease-specific survival, p = 0.01), a polymorphous tumor cell population (overall survival, p = 0.007; disease-specific survival, p = 0.008), and necrosis (overall survival, p = 0.007; disease-specific survival, p = 0.056). However, because these three parameters were associated with each other, none of them remained of independent predictive value for outcome by multivariate analysis.
No prognostic significance was found for tumor thickness, level of invasion, ulceration, mitotic index, or nerve/nerve sheath involvement. Thus, the histologic parameters relevant for the prognosis of squamous mucosa differ significantly from those of cutaneous melanomas.
LEPTOMENINGEAL Arch Pathol 1973;95:392
Average age 29 years
Frontal and temporal lobes most common location
Almost never metastasize outside of the CNS
1/3 of cases associated with pre-existing giant congenital nevi
Occasionally associated with nevus of OtaAverage survival is 5 months
MEDIASTINAL Primary Malignant Melanoma of the Anterior Mediastinum in a Child Eugene Vlodavsky, M.D.; Ofer Ben-Izhak, M.D.; Lael-Anson Best, M.D.; Hedviga Kerner, M.D.
From the Departments of Pathology (E.V., H.K., O.B.-I.) and Thoracic Surgery (L.B.), Rambam Medical Center, Haifa, Israel.
Am J Surg Pathol 2000;24:747-749 Abstract quote Primary malignant melanoma of the mediastinum is extremely rare.
We report a case not previously reported of primary malignant melanoma located in the mediastinum in a 11-year-old boy. The tumor could not be completely resected as a result of extensive invasion of the large blood vessels. Histologically, the tumor was heavily pigmented and composed of vague fascicles of spindle cells intermingled with epithelioid cells. Immunohistochemical analysis showed vimentin, S-100 protein, Melan-A, and HMB-45 immunoreactivity in most of the tumor cells. Nearly 50% of the tumor cells were also positive for p53.
It is suggested that primary malignant melanoma of the anterior mediastinum may have a histogenetic relationship to the recently described aggregates of nevus cells in the thymus or mediastinal lymph nodes.
Pediatr Dermatol 1992;9:37
Rare phakomatosis
Increased risk for neuroectodermal cancers, rhabdomyosarcoma, and Dandy-Walker syndrome
Neurocutaneous melanosis in association with encephalocraniocutaneous lipomatosis.Ahmed I, Tope WD, Young TL, Miller DM, Bloom KE.
Departments of Dermatology, Laboratory Medicine and Pathology, Opthalmology, and Pediatrics, University of Minnesota.
J Am Acad Dermatol 2002 Aug;47(2 Pt 2):S196-200 Abstract quote We describe a white female infant with neurocutaneous melanosis (NCM) and encephalocraniocutaneous lipomatosis (ECCL). Multiple, giant and small congenital melanocytic nevi (CMN) were observed on the head, neck and trunk and involved 70% of body surface area. Histologic examination of several CMN revealed atypical nodular proliferations of dermal nevomelanocytes.
In a small (<1 cm) truncal CMN, single and dyscohesive intraepidermal nests of atypical nevomelanocytes simulating a superficial spreading melanoma, were observed. The placenta was grossly normal and histologically demonstrated multiple banal appearing nevomelanocytes within the stroma of its villi. At the 17-month follow-up no evidence of primary or metastatic melanoma was present.
This previously undescribed association of NCM, ECCL and placental nevomelanocytes provides strong support for the hypothesized causal role of anomalous neural crest morphogenesis and migration in the development of all three disorders. The genetic mechanism underlying these complex birth defects has been hypothesized to result from the action of lethal autosomal dominant genes surviving by mosaicism.
OCULAR MELANOMA ORAL
Department of General Pathology, Dental School, University of São Paulo, São Paulo, Brazil.
Oral mucosal melanoma is rare and reported to be more aggressive than its cutaneous counterpart. Due to the rarity of this entity, data on epidemiology, tumor behavior, treatment, follow-up, and survival of patients are mainly based on single case reports. The few existing series of patients show that oral mucosa melanoma has its peak between 41 and 60 years of age, and male to female ratio is 2:1. Preferred oral sites include hard palate and maxillary alveolar crests. Risk factors have not been clearly identified, and surgical treatment is still the treatment of choice for oral mucosal melanomas.
The authors retrospectively studied 35 patients with primary melanoma of the oral cavity to report their clinical and pathological features, such as age, sex, site of the tumor, metastasis, treatment, response to therapy, and outcome. We found no significant sex predominance, and the mean age of the patients was 60.6 years, with a range from 9 to 91 years. The majority of the patients (71.42%) had palate commitment, and invasive histopathological aspect was observed in 80% of the specimens (grade 3). Long-distance metastasis was found in 60% of the cases.
Fourteen patients were submitted to wide surgical resections, with local relapse being observed in 11 of them (78.5%).
The authors suggest that improved outcome in oral malignant melanoma requires the development of new therapies and the prevention of distant metastasis.
Division of Diagnostic Sciences, Orofacial Pain and Oral Medicine Center, University of Southern California, School of Dentistry, Los Angeles, CA, USA.
Oral mucosal melanoma (OMM) is an extremely rare malignancy, accounting for < 0.5% of all melanomas and all oral malignancies. The rarity of OMM, the heterogeneity in clinical and histopathologic appearances, and the paucity of molecular and genetic studies to date have limited our knowledge of the etiopathogenesis of these cancers.
A 39-year-old Hispanic male presented for evaluation of a large, pigmented, plaque-like and nodular growth of the maxillary gingival and palatal mucosa. On presentation, a presumptive clinical diagnosis of mucosal melanoma was made, which was confirmed by incisional biopsy with subsequent histopathologic evaluation. Macroscopically, the morphology and highly pigmented nature of the tumor was suggestive of a rarer subtype of melanoma known as animal-type melanoma, also referred to as pigmented epithelioid melanocytoma.
However, microscopically, the tumor showed histopathologic features consistent with a high-grade acral (mucosal) lentiginous melanoma with overt cytomorphologic features of malignancy in addition to showing prominent pigment synthesis resembling animal-type melanoma. A detailed search of the literature did not identify a previous report of OMM with prominent pigment synthesis resembling animal-type melanoma.
Identification of melanoma subtypes has specific implications for therapeutic approach, and thus their recognition is important to successful patient management.
Lentigo maligna with spread onto oral mucosa.Kroumpouzos G, Frank EW, Albertini JG, Krivo JM, Ramsey ML, Tyler WB, Cohen LM.
320 Needham St, Suite 200, Newton, MA 02464
Arch Dermatol 2002 Sep;138(9):1216-20 Abstract quote BACKGROUND: Lentigo maligna (LM) is a form of melanoma in situ most often seen in white patients on sun-exposed areas, primarily the head and neck. Spread of LM onto the conjunctiva has been reported. There have been no reports of LM extending onto oral mucosa.
OBSERVATIONS: We report 4 cases of LM in white women with contiguous spread from perioral areas to oral mucosa. The locations of the primary lesions were the vermilion of the lip, vermilion and perioral skin, cheek, and cutaneous aspect of the lip. Three cases showed focal histopathologic evidence of invasion during the course of the disease. The lesions ran a prolonged course characterized by repeated recurrences after surgery. Three of the cases required a complicated reconstruction after surgical excision. Mohs surgery with rush permanent (paraffin-embedded) sections resulted in a long remission in 2 cases, while in 1 patient, treatment with carbon dioxide laser was unsuccessful.
CONCLUSIONS: In a perioral distribution, LM can spread onto oral mucosa. This clinical presentation may cause significant long-term morbidity, as indicated by a high recurrence rate and/or progression to invasive melanoma. The oral mucosa should be examined in patients with atypical pigmented perioral lesions.
Malignant melanoma of the oral mucosa in a 17-year-old adolescent girl.D'Silva NJ, Kurago Z, Polverini PJ, Hanks CT, Paulino AF.
Department of Oral Medicine, Pathology, and Oncology, University of Michigan School of Dentistry, Ann Arbor, Mich 48109, USA.
Arch Pathol Lab Med 2002 Sep;126(9):1110-3 Abstract quote Mucosal melanomas of the oral cavity are rarely seen in the United States. The hard palate is the most common intraoral site. This unusual case occurred in the oral cavity of a 17-year-old Asian girl, who presented to her dentist with complaints of pain and swelling in the upper jaw. The lesion was distal and palatal to the maxillary left second molar, which was vital. Interestingly, the clinical presentation was a hyperplastic, tender lesion that bled when probed.
Histopathologically, the biopsy demonstrated a sheet of spindle-shaped cells arranged in nests and fascicles. The nuclei were vesicular, oval to spindle-shaped, and some contained nucleoli that were distinguishable but not prominent. No melanin pigment was observed in the lesion.
Tumor cells strongly expressed S100 protein, gp100 (HMB-45), and microphthalmia transcription factor, and variably expressed MART1, but not cytokeratins, CD34, or muscle-specific actin. The histopathologic features and immunohistochemical findings are consistent with a diagnosis of malignant melanoma.
OVARY Malignant melanoma involving the ovary: a clinicopathologic and immunohistochemical study of 23 cases.
Gupta D, Deavers MT, Silva EG, Malpica A.
Department of Pathology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Am J Surg Pathol. 2004 Jun;28(6):771-80. Abstract quote
Ovarian malignant melanoma (MM), primary or metastatic, is an extremely rare tumor and in the absence of a previous diagnosis can represent a diagnostic challenge.
We present the clinicopathologic and immunohistochemical features of 23 cases seen in our institution over a period of 40 years (1962-2001). The patients' age ranged from 14 to 53 years (mean 35.7 years). Ethnicity was known in 19 patients: 14 white, 4 Hispanic, and 1 black.
A previous history of MM was definitively obtained in 14 patients; in these cases, the interval between the primary MM and the ovarian metastasis ranged from 15 to 228 months (mean 77.7 months). The tumor was unilateral in 19 and bilateral in 4 cases. The tumor size ranged from 4.5 to 23 cm (average 10 cm); the melanoma arising in a cystic teratoma was 0.2 mm in thickness. The tumor was grossly pigmented in 8 cases (35%).
The architectural pattern was nodular (8 cases), diffuse (6 cases), nodular and diffuse (5 cases), nested (3 cases), and lentiginous arising in a teratoma (1 case). Follicle-like spaces were seen in 8 cases, pseudo-glandular areas in 1 case, pseudo-myxoid areas in 1 case, and cords in 1 case. The tumor cell type was epithelioid in 19 cases, spindled in 2 cases, mixed epithelioid and spindled in 1 case, and small cell in 1 case. Nucleoli were prominent in 18 cases, and nuclear inclusions were present but rare in the majority of cases. Nuclear grooves were seen in 3 cases. Necrosis was extensive in 8 cases, focal in 10 cases, and was absent in 5 cases.
In 8 cases, initial diagnoses included sex cord stromal tumor, germ cell tumor, sarcoma, or undifferentiated carcinoma. S-100 was positive in 18 of 19 cases, HMB-45 in 17 of 20 cases, MART-1 in 13 of 15 cases, tyrosinase in 10 of 15 cases, and Mitf in 8 of 14 cases. Inhibin was positive in 3 of 14 cases. Calretinin was focally positive in 1 of 12 cases.
Treatment performed in 18 of the cases are as follows: oophorectomy with/without chemotherapy (10); total abdominal hysterectomy with bilateral salpingo-oophorectomy with/without chemotherapy (6); vaginal hysterectomy, bilateral salpingo-oophorectomy, and chemotherapy (1); and total abdominal hysterectomy with salpingo-oophorectomy (1).
Follow-up ranging from 2 to 96 months was available in 18 patients. All but one had metastases in other organs, most often in the lungs. Thirteen patients died of disease (range 2-76 months), 3 are alive with disease (6-18 months), and 2 have no evidence of disease at 24 and 96 months; one was the patient with melanoma arising within a teratoma.
In conclusion, MM involving the ovary is a rare disease, predominantly seen in women of reproductive age, and is associated with a poor prognosis. The tumor is most often metastatic from another site and is unilateral in most cases. Nodular or diffuse pattern and epithelioid cell type are most frequently seen, and the tumor can be mistaken for germ cell and sex cord stromal tumors. S-100 is the most sensitive marker. MART-1 was positive in the few cases that were negative with HMB-45. Inhibin can be focally positive in some cases.SINONASAL
Sinonasal tract and nasopharyngeal melanomas: a clinicopathologic study of 115 cases with a proposed staging system.Thompson LD, Wieneke JA, Miettinen M.
Am J Surg Pathol 2003 May;27(5):594-611 Abstract quote Primary sinonasal tract mucosal malignant melanomas are uncommon tumors that are frequently misclassified, resulting in inappropriate clinical management.
A total of 115 cases of sinonasal tract mucosal malignant melanoma included 59 females and 56 males, 13-93 years of age (mean 64.3 years). Patients presented most frequently with epistaxis (n = 52), mass (n = 42), and/or nasal obstruction (n = 34) present for a mean of 8.2 months.
The majority of tumors involved the nasal cavity (n = 34), septum alone, or a combination of the nasal cavity and sinuses (n = 39) with a mean size of 2.4 cm. Histologically, the tumors were composed of a variety of cell types (epithelioid, spindled, undifferentiated), frequently arranged in a peritheliomatous distribution (n = 39). Immunohistochemical studies confirmed the diagnosis of sinonasal tract mucosal malignant melanomas with positive reactions for S-100 protein, tyrosinase, HMB-45, melan A, and microphthalmia transcription factor.
Sinonasal tract mucosal malignant melanomas need to be considered in the differential diagnosis of most sinonasal malignancies, particularly carcinoma, lymphoma, sarcoma, and olfactory neuroblastoma. Surgery accompanied by radiation and/or chemotherapy was generally used. The majority of patients developed a recurrence (n = 79), with 75 patients dying with disseminated disease (mean 2.3 years), whereas 40 patients are either alive or had died of unrelated causes (mean 13.9 years).
A TNM-type classification separated by anatomic site of involvement and metastatic disease is proposed to predict biologic behavior.
THYMUS Malignant Melanoma in the Thymus
Hiroaki Fushimi, M.D.; Kiyoshi Kotoh, M.D.; Dai Watanabe, M.D.; Yoshiro Tanio, M.D.; Tatsuji Ogawa, M.D.; Shinichiro Miyoshi, M.D.
From the Departments of Pathology (H.F., K.K.), Internal Medicine (D.W., Y.T.), and Surgery (T.O.), Osaka Prefectural General Hospital, Sumiyoshi-ku, Osaka, Japan; and the Department of Surgery, Osaka University, Medical School, Suita, Japan (S.M.).
Am J Surg Pathol 2000;24:1305-1308 Abstract quote
A case of malignant melanoma in the thymus is reported.
Diagnostic imaging demonstrated a left anterior mediastinal mass in a patient with giant pigmented nevus without malignant change.
Histologic and cytologic specimens obtained from the tumor revealed that the tumor was malignant melanoma. Surgery revealed malignant melanoma in the left lobe of the thymus. Many cell nests of pigmented nevi were observed throughout the thymus. The malignant melanoma was thought to have originated from the nevocellular nevus in the thymus.
This is the first report of malignant melanoma in the thymus.
URETHRA Primary Malignant Melanoma of the Urethra
A Clinicopathologic Analysis of 15 CasesEsther Oliva, M.D.; Timothy R. Quinn, M.D.; Mahul B. Amin, M.D.; John N. Eble, M.D.; Jonathan I. Epstein, M.D.; John R. Srigley, M.D.; Robert H. Young, M.D.
From the Departments of Pathology, Harvard Medical School and the James Homer Wright Pathology Laboratories of the Massachusetts General Hospital, Boston, Massachusetts, U.S.A. (E.O., R.H.Y.), Pathology Services Incorporated, Cambridge, Massachusetts, U.S.A. (T.R.Q.), Emory University, Atlanta, Georgia, U.S.A. (M.B.A.), Indiana University, Indianapolis, Indianapolis, U.S.A. (J.N.E.), John Hopkins Hospital, Baltimore, Maryland, U.S.A. (J.I.E.) and McMaster University, Hamilton and The Credit Valley Hospital, Mississauga, Ontario, Canada (J.R.S.).
Am J Surg Pathol 2000;24:785-796 Abstract quote The clinical and pathologic features of 15 primary urethral melanomas occurring in patients (nine women and six men) age 44 to 96 years (mean age, 73 yrs) are described.
In the men the tumor involved the distal urethra. In eight women it involved the distal urethra, usually the meatus; both the distal and proximal urethra were involved in one woman. The tumors were typically polypoid and ranged from 0.8 to 6 cm (mean, 2.6 cm) in maximum dimension. A vertical growth phase was present in all tumors, with a prominent nodular component in seven of them. A radial growth phase was seen in nine tumors. The depth of invasion ranged from 2 to 17 mm. The tumors had diffuse, nested, storiform, or mixed growth patterns. The neoplastic cells typically had abundant eosinophilic cytoplasm, large nuclei with prominent nucleoli, and brisk mitotic activity. Melanin pigment was seen in 12 tumors but was conspicuous in only six.
At the time of diagnosis, 13 tumors were confined to the urethra and two patients had lymph node metastasis. Nine patients died of disease 13 to 56 months after initial diagnosis and treatment, and one patient had a local recurrence at 4 years and subsequently died of sepsis 1 year later. Three patients were alive and well at 11 months, 23 months, and 7 years. One patient died at the time of the initial operation, and one died of a ruptured aortic aneurysm at 3 years without evidence of melanoma at autopsy.
Primary malignant melanomas of the urethra, one fifth of which are amelanotic, must be included in the differential diagnosis of a number of primary neoplasms that involve the urethra, including transitional cell carcinoma, sarcomatoid carcinoma, and sarcomas. Conventional prognostic factors, such as depth of invasion or tumor stage, do not seem to play as important a role in predicting survival as the mucosal location and the nodular growth present frequently in these tumors.
VAGINA
From the *Biomed-Molec-Serv Am Weiher 14, Kalkar, Germany; daggerDepartment of Pathology, University of Tennessee Health Science Center, Memphis, TN; double daggerDivisions of Dermatology and Dermatopathology, Albany Medical College, Albany, NY; and section signSt. Peter's Hospital Professional Building, Albany, NY.
Vulvovaginal melanomas are rare and their etiology is unknown. Genital mucosal human papillomavirus (HPV) 16 has been identified in both cutaneous and mucosal melanoma, suggesting that it might play a role in the pathogenesis or progression of melanoma.
In this study, we investigated the prevalence of HPV DNA by using a broad spectrum of degenerate and type-specific primers for genital-mucosal, epidermodysplasia verruciformis-associated (EV), and cutaneous HPV types in 6 vulvar and 3 vaginal melanomas. The patients were mostly postmenopausal women (8/9), had a mean age of 67 years (range, 44-85 years), and had mucosal lentiginous (7) or nodular (2) melanomas. In the adjacent skin/mucosa, mucosal melanosis was found in 5, lichen sclerosus or a lichenoid mucositis in 4, and blue nevi in 2 women. With nested polymerase chain reaction techniques followed by direct sequencing, HPV DNA was identified in 6 of 9 (67%) melanomas; these were either cutaneous (HPV 3) (4/9) or epidermodysplasia verruciformis-associated types (HPV 38, Z95969, AJ00151) (4/9). Epidermodysplasia verruciformis-associated HPV (type 15) was found solely in 1/10 (10%) normal vulvar controls. Genital-mucosal HPV types were not detected either by degenerate nested polymerase chain reaction or type-specific probes for HPV 16.
We propose that the above findings are not coincidental but may represent a molecular record of HPV involvement in pathogenesis or progression of melanoma, which is consistent with the strong but poorly defined association of cutaneous HPV types with nonmelanoma skin cancers. The theory that HPV may act as a cofactor in melanoma development deserves further clinical and experimental investigations.
Vaginal Melanoma: A Clinicopathologic and Immunohistochemical Study of 26 Cases
Deepali Gupta, M.D.; Anais Malpica, M.D.; Michael T. Deavers, M.D.; Elvio G. Silva, M.D.Am J Surg Pathol 2002; 26(11):1450-1457 Abstract quote
Malignant melanomas of the vagina are rare tumors. In this study we present the clinicopathologic features and immunohistochemical analysis of 26 such cases seen in our institution over a period of 30 years.The patients' age ranged from 38 to 90 years (mean 60 years); three patients were premenopausal. Ethnicity was known in 24 patients: 20 white, 2 hispanic, 1 black, and 1 Asian. The most common presenting symptom was vaginal bleeding, followed by vaginal mass.
Grossly, the tumor was polypoid-nodular in the majority of cases. The neoplastic cells were epithelioid in 15 cases and spindled in three cases; eight cases had both cell types. Vascular-lymphatic invasion was seen in six cases and perineural invasion was seen in four cases. S-100 was strongly and diffusely positive in 25 of 26 cases (96%). HMB-45 was strongly positive in 16 (62%), 3 (11%) were focally positive, 1 case showed a rare positive cell, and 6 (23%) were negative. With MART-1, 20 cases (77%) were strongly positive, 1 (4%) showed a rare weakly positive cell, and 5 (19%) were negative. Twenty-one cases (81%) expressed tyrosinase and 20 (77%) expressed microphthalmia transcription factor. Twenty cases were Chung's level IV, 3 were level III, and 2 were level II.
The patients were treated as follows: anterior exenteration with or without lymph node dissection and with or without radiotherapy (RT) or chemotherapy (CT) (7 cases), wide local excision with or without lymph node dissection and RT/CT (10 cases), hysterectomy with vaginectomy with or without RT/CT (3 cases), vaginectomy with RT (1 case), RT (1 case), and RT and CT (1 case). One patient had palliative RT for the brain metastasis only. Follow-up was available in 23 patients ranging from 3 to 276 months (median 18 months). Local recurrence after primary treatment was seen in six patients and distant metastases in 11 patients. Fifteen patients died of the disease (3-83 months), 4 have no evidence of disease (5-24 months), and 4 are alive with disease (6-276 months).
This study confirms the poor prognosis of patients with vaginal melanoma. S-100 remains the most sensitive marker for these tumors. HMB-45 is negative in 23% cases of vaginal melanoma. Tyrosinase and MART-1 are useful markers when S-100 is negative or only focally positive.
VULVA
Vulvar melanoma: A report of 20 cases and review of the literature.
Wechter ME, Gruber SB, Haefner HK, Lowe L, Schwartz JL, Reynolds KR, Johnston CM, Johnson TM.
J Am Acad Dermatol. 2004 Apr;50(4):554-62. Abstract quot
BACKGROUND: Vulvar melanoma is the second most common vulvar malignancy and represents a significant women's health issue.
OBJECTIVE: To report experience with 21 cases of vulvar melanoma in 20 patients and to review the literature about the condition.
METHODS: Parameters retrospectively reviewed included age at diagnosis, family history of melanoma, location on the vulva, atypical nevi, Breslow depth, ulceration status, histologic pattern, presenting signs and symptoms, and the results of sentinel lymph node biopsy. Molecular characterization of the melanocortin type 1 receptor was performed in 1 patient.
RESULTS: A family history of cutaneous melanoma was present in 15% of cases. The mean Breslow depth was 2.8 mm (range, 0.0-11.0 mm). Ten patients successfully underwent sentinel lymph node biopsy, results of which were positive in 2 (20%). Reported for the first time is that one patient had a germline mutation in the melanocortin type 1 receptor.
CONCLUSION: Vulvar and cutaneous melanoma behave similarly despite their unique pathogeneses. Sentinel lymph node biopsy can be performed successfully for vulvar melanoma.
Vulvar melanoma: Diffuse melanosis and metastasis to the placenta.
Alexander A, Harris RM, Grossman D, Bruggers CS, Leachman SA.
J Am Acad Dermatol. 2004 Feb;50(2):293-8. Abstract quote
Mucocutaneous melanoma, including vulvar melanoma, is rare and has a worse prognosis and higher recurrence rate than traditional cutaneous melanoma. Diffuse cutaneous melanosis is another rare clinical presentation of metastatic melanoma. It is essential for dermatologists to be alerted to rare presentations of melanoma, to facilitate early detection.
We present the first case to our knowledge of metastatic vulvar melanoma with diffuse cutaneous melanosis in a pregnant young woman. Despite the occurrence of placental metastasis, a healthy, unaffected baby was born. This case exemplifies the aggressiveness of vulvar melanoma. The genitalia should be included in routine total body skin examinations. Pregnant women with generalized melanosis may be at increased risk for placental metastasis of melanoma.
Pregnancy does not alter the incidence or prognosis of melanoma; however, patients with a poor prognosis or high recurrence risk should be informed of potential pregnancy complications associated with melanoma recurrence or metastasis.Macpherson and Pincus. Clinical Diagnosis and Management by Laboratory Methods. Twentyfirst Edition. WB Saunders. 2006.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fifth Edition. Mosby Elesevier 2008
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