Pigments of the Gastrointestinal Tract: A Comparison of Light Microscopic and Electron Microscopic Findings

It is now apparent that light microscopy and histochemistry failed to identify correctly the nature and composition of pigments in various gastrointestinal tract melanoses. In most instances it was thought that the pigment was melanin or a melanin-like substance. Electron microscopy (EM) and electron-probe energy dispersive x-ray analysis have rectified these errors and have shown the following: in melanosis coli the pigment granules contain lipofuscin; in melanoses ilei the pigment granules may contain either silicates and titanium or hemosiderin; and in melanosis duodeni the pigment granules contain iron sulfide. In melanosis esophagi it is not clear what the pigment is; it could be melanin or lipofuscin.     

Incidence of melanocytic lesions of the conjunctiva in a review of 10 675 ophthalmic specimens

During the study period, 10,675 human ophthalmic specimens were received at The Henry C. Witelson Ophthalmic Pathology Laboratory and Registry, McGill University, Montreal, Canada. Of those, 271 were conjunctival lesions (2.5%), with 101 being classified as melanocytic: 50 (49.5%) nevi, 36 (35.6%) primary acquired melanoses, and 15 (14.9%) melanomas. After exclusion of referred cases, 85 lesions were included in the study: 44 (51.7%) nevi, 33 (38.8%) primary acquired melanoses, and 8 (9.4%) melanomas. The most prevalent location was the bulbar conjunctiva. Conjunctival melanomas were most commonly found in an older age group than primary acquired melanosis or nevi. Conjunctival nevi were subdivided into compound (32.9%), subepithelial (16.4%), and junctional (2.3%). Primary acquired melanosis were further classified into primary acquired melanosis with atypia (8.2%) and primary acquired melanosis without atypia (30.5%). Primary acquired melanoses was the predisposing lesion in 75% of the cases of melanoma. In our sample, referral bias could alter the distribution of conjunctival pigmented lesions, with a shift toward the malignant end.     

A comparison of the ultrastructure of pigment granules in melanosis ilei and pulmonary lymph nodes

Two cases of melanosis ilei were studied, in which grossly visible blackish pigmentation of the ileal mucosa was incidentally discovered at autopsy. Light microscopy showed that the pigment granules lay within macrophages in atrophic Peyer's patches. Ultrastructural studies showed that the pigment granules were heterolysosomes containing crystalline material, particles, granules and, occasionally, lipid droplets. The morphological similarity between these pigment granules and granules in pulmonary macrophages was established through ultrastructural studies of pulmonary lymph nodes obtained during routine autopsies. These data, plus results of past electron-probe X-ray analytic studies by us and others, leads us to conclude that the pigment granules in melanosis ilei contain exogenous material derived from inspired and ingested materials.     

Two cases of early-stage esophageal malignant melanoma with long-term survival

Herein is described two patients with early-stage primary malignant melanoma of the esophagus with long-term survival who were treated with esophagectomy. Both tumors had similar pathological findings, and were mainly at the stage of radial growth phase. Widespread melanoses were present in the mucosa surrounding the tumors in both cases. The two patients recovered uneventfully after surgery and were in remission at follow up of 33 months and 53 months.     

Multifocal malignant melanoma arising in vesicovaginal melanosis

An 80-year-old white woman developed vulvar melanosis and malignant melanoma of the labia majora and clitoris and underwent a simple vulvectomy. She subsequently developed melanosis of the urinary bladder and presented 3 years later with multifocal malignant melanoma involving the vagina, urethra, and urinary bladder in a background of extensive melanosis with variable degrees of atypia. She underwent radical surgery but died 18 months later with liver metastases and liver failure. Malignant melanoma is uncommon in the vulva and vagina and is rare in the urinary bladder. This case illustrates the previously described association between melanosis and malignant melanoma. The unusual features are the widespread distribution of the melanosis (vagina and bladder) and the subsequent development of multifocal malignant melanoma.     

Primary malignant melanoma of the esophagus with diffuse melanocytic atypia and melanoma in situ

Primary malignant melanoma is an unusual lesion in the esophagus that is not infrequently seen in association with melanosis. A case of esophageal invasive malignant melanoma with melanosis is described in which the melanosis exhibited melanocytic atypia extending through to melanoma in situ. The authors know of no previously reported such finding.     

Primary acquired melanosis of the conjunctiva is melanoma in situ

This essay places the concept of "primary acquired melanosis" of the conjunctiva in historical perspective and shows that it and its analogs, namely, lentigo-melanosis (Hutchinson), melanotic freckle (Hutchinson), melanose circonscrite precancereuse (Dubrueilh), melanotische precancerose (Miescher), lentigo maligna (Clark), precancerous melanosis (Reese), benign, precancerous, and cancerous melanosis (Zimmerman), atypical melanocytic hyperplasia (Silver et al.), and benign acquired melanosis (Zimmerman), are synonyms for melanoma in situ. The issue is not merely semantic or philosophical; it is urgently practical. If a clinician takes literally the meaning of a lesion designated "benign melanosis" and considers it to be benign, rather than the malignant melanoma that it actually is, a patient who bears that flat pigmented lesion may one day die of metastasis from an elevated sequella of it. The same is true of "primary acquired melanosis," which is not simply a condition of blackening by melanin, but a flat melanoma that, if not removed completely, may give rise one day to metastases that cause death. To avoid such misconstructions, we advocate naming melanomas in all organs "melanoma" and those that are confined to epithelial structures "melanoma in situ." Euphemisms like lentigo maligna and primary acquired melanosis are evasions of the diagnosis of melanoma, and use of them may be harmful. For that reason, they should be eschewed.     

Primary malignant melanoma of the urinary bladder.

Primary malignant melanoma is an unusual neoplasm in the urinary bladder that is infrequently found in association with melanosis. We report a case of bladder-invasive malignant melanoma with melanosis in which the melanosis exhibited melanocytic atypia extending through to melanoma in situ and was diagnosed by immunohistochemical techniques using a monoclonal antibody, HMB-45. To our knowledge, such findings have not been reported previously.     

Peritoneal melanosis combined with serous cystadenoma of the ovary: a case report and literature review

Benign peritoneal melanosis is extremely rare and traditionally occurs in association with ovarian dermoid cysts, but rarely with peritoneal cyst, enteric duplication cyst or gastric triplication. The pathogenesis of peritoneal melanosis, in particular, the origin of the pigment-producing cells is unclear. We describe a case of peritoneal melanosis that was associated with ovarian serous cystadenoma in a young woman. Ovarian serous cystadenoma has not been previously described as a combined lesion of peritoneal melanosis. Based on the extremely rare incidence of this lesion and heterogeneous combined lesions, the possibility of an incidentally found, coexisting lesion couldn't be excluded. Here, we suggest that peritoneal mesothelial cells pinched off during the developmental period might be a source of pigment-producing cells.     

Melanosis of the appendix: prevalence, distribution and review of the pathogenesis of 47 cases

The appendix is reported to be a common site for melanosis, especially at autopsy although to date there have been few studies expanding or qualifying this statement. Based on 47 cases identified from a series of 636 consecutive surgical specimens the prevalence, pattern of distribution, nature of the pigment and current knowledge of the aetiology and pathogenesis of melanosis of the appendix is reviewed and compared with melanosis coli.     

Colonic lymphoid hyperplasia in melanosis coli

We describe the case of a patient with Rett syndrome, a syndrome characterized by progressive infant encephalopathy, developmental delay, dementia, autism, ataxia, microcephaly, spastic paraparesis, and autonomic neuropathy with constipation. At colonoscopy, multiple foci of tiny white, sessile, polypoid lesions were seen throughout the colon and rectum, mimicking the appearances of small hyperplastic or adenomatous polyps, associated with generalized melanosis coli. This is the first case to our knowledge describing melanosis coli in a patient with Rett syndrome. As melanosis pigment deposition is characteristically not seen in lymphoid tissue, the lymphoid tissue was identifiable at endoscopy as multiple white nodules mimicking generalized colonic polyposis throughout the colon. We discuss the likely mechanisms of lymphoid hyperplasia and coexistent melanosis coli in Rett syndrome.     

Melanosis coli is associated with an increase in colonic epithelial apoptosis and not with laxative use

We have investigated the clinical presentation, laxative use and histopathology of 38 patients with a histological diagnosis of melanosis coli and measured the colonic epithelial apoptosis in these cases. The presence of lipofuscin was confirmed in all cases. Fifteen of the cases had constipation, whilst eight had diarrhoea. Neither constipation nor diarrhoea was present in 13 cases and both were present, at different times, in two. Laxatives had been used in all those with constipation, in only one with diarrhoea and in none of the others. The mean apoptotic count was significantly increased in those with melanosis coli compared with the controls. In the majority of cases with constipation there was no other abnormality, whilst an additional diagnosis was present in the majority of the remainder. Colonic epithelial apoptosis was increased in melanosis coli and the majority of cases were not associated with laxative use. These results support the proposed role of apoptosis in melanosis coli, but indicate that melanosis coli is a non-specific marker of increased apoptosis with many possible causes, of which the use of laxatives is only one.     

Melanosis coli--histochemical and immunohistochemical comparison of the pigments of melanosis coli and Dubin-Johnson syndrome

We compared the pigment of melanosis coli with the pigment of Dubin-Johnson syndrome, melanin, and lipofuscin. The pigment of melanosis coli appeared similar to lipofuscin in that it stained positively with periodic acid-Schiff, oil red-0 and Victoria blue stains and revealed negative reactions to the immunohistochemical stains for S-100 protein and neuron specific enolase, but had similarity to melanin as shown by the positive reaction to Fontana-Masson stain and negative autofluorescence. The pigment of Dubin-Johnson syndrome showed the same histochemical and immunohistochemical characteristics as that of melanosis coli. The results indicate that the pigments of melanosis coli and Dubin-Johnson syndrome are identical and are variants of lipofuscin.     

Melanosis of the choroid plexus, ependyma, subependymal neuroglia, and dentate and trigeminal motor nuclei: observations on the choroidal and ependymal cilia

Melanosis of the choroid plexus, ependyma, subependymal neuroglia of the fourth ventricle, and dentate and trigeminal motor nuclei was found in a 50-year-old man who died with cor pulmonale, hypertensive cardiovascular disease, and intracerebral hemorrhage. This case is the first known example of melanosis not associated with neurocutaneous melanosis to involve multiple structures of the brain. Nonenzymatic conversion of lipofuscin into melanin is suggested as the mechanism of the melanosis. Cilia of the choroidal epithelium and ependyma were identified in this case, despite a long delay in postmortem examination. These observations on choroidal epithelium confirm previous reports that the choroid plexus of man is ciliated, as in other mammals and lower vertebrates.     

Der gekreuzte spino-adductorische Reflex

Zusammenfassung Beim Menschen kann fast konstant durch Abklopfen der Spina ossis ilei sup. ant. ein Reflex dergekreuzten Adductoren hervorgerufen werden. Wie die genauere Analyse zeigt, handelt es sich um einen echten und reinen, gekreuzten Reflex. Eine Erklärung des Phänomens auf dem Wege der Übertragung des Reizes durch den Knochen erscheint ausgeschlossen.     

Differential immunoreactivity of melanocytic lesions of the conjunctiva

AIMS: To evaluate the expression of S100NKI/C3 and HMB45 antigens in melanocytic lesions of the conjunctiva and the ability of HMB45 to aid assessment of neoplasia. METHODS AND RESULTS: Stored formalin-fixed specimens of conjunctival melanomas and primary acquired melanosis were considered as participants and conjunctival naevi and racial melanosis as controls. Ninety-seven conjunctival melanocytic lesions were analysed using formalin-fixed paraffin-embedded material. These included 20 melanomas arising in the context of primary acquired melanosis (PAM), 22 melanomas arising without evidence of pre-existing PAM, seven cases of PAM with atypia, nine cases of PAM with no atypia, 35 conjunctival naevi and four cases of racial melanosis. S100 and NKI/C3 were similarly expressed in all lesions, with at least one of these markers positive in 100% of the lesions examined. HMB45 was expressed in 72.7% of primary melanomas and 85% of melanomas in the context of PAM; 42.8% of PAM with atypia expressed HMB45 while it was expressed in 11.1% of PAM without atypia and 8.5% of naevi. Racial melanosis cases did not express HMB45. S100 and NKI/C3 were expressed to a similar extent in all groups. CONCLUSIONS: S100 and NKI/C3 are useful markers to assess the extent of melanocytic lesions in the conjunctiva. HMB45 immunoreactivity can act as a useful aid to histopathology for the distinction of benign from malignant conjunctival lesions, particularly in the context of primary acquired melanosis.     

Pseudomelanosis duodeni: a case report with electron-probe X-ray analysis.

Pseudomelanosis of the duodenum is rare. Only 17 cases have been documented in the world literature. A 59-year-old man presented to Bankstown Hospital, New South Wales with dysphagia. On endoscopy, he was found to have melanosis of the duodenum in addition to oesophageal ulceration. It has been previously suggested that the pigment ferrous sulphide is derived from gastro-intestinal bleeding and lodged in the macrophages. A detailed examination of the pigment, including X-ray probe micro-analysis at various levels of the intestinal epithelium as well as in macrophages is presented.     

Yellow-brown spindle bodies in mesenteric lymph nodes: a possible relationship with melanosis coli

Four cases are described in which spindle-shaped, yellow-brown bodies were seen in the mesenteric lymph nodes of patients with melanosis coli. A comparison of the staining reactions and ultrastructural appearances of the spindle bodies and melanosis pigment suggest that they are related within the broad group of lipofuscins and that the spindle bodies are formed as a result of coalescence of lysosomes containing the pigment.     

Invasive ductal carcinoma of the breast associated with extensive melanin melanosis: a case report and review of the literature

Extensive melanosis of breast tissue due to melanin in the absence of involvement by melanoma either primary or secondary has been rarely encountered. Herein we report a first and unique case of extensive macroscopic and microscopic melanosis of mammary parenchyma between carcinoma cells due to melanin in a patient with a poorly differentiated invasive ductal carcinoma of the breast with no evidence of melanocytic differentiation or melanoma. In contrast to previously reported cases in the literature, there is no breach of dermal-epidermal junction and there is no dermal infiltrate in the skin overlying the carcinoma, or Pagetoid disease in the nipple.     

Acral lentiginous melanoma and its precursor--heterogeneity of palmo-plantar melanomas

Malignant melanomas occur with high frequency in the volar skin and with heterogeneity consisting of acral lentiginous melanoma (ALM) and nodular melanoma in Japan. Analytical study has revealed the precursor of ALM which we designate plantar or palmar premalignant melanosis (PPM), and whose cellular characteristics appear to be similar to those of pagetoid premalignant melanosis or the radial phase of superficial spreading melanoma (SSM).