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Biomedical subjects

J H Graham

Publications and source records attributed to J H Graham.

At least 19 recordsLinked to original sources

Balloon cell malignant melanoma of the skin. A clinicopathologic study of 34 cases with histochemical, immunohistochemical, and ultrastructural observations.

Balloon cell malignant melanoma (BCMM) is a rare histologic variant of malignant melanoma (MM). Thirty-four patients with BCMM from the files of the Armed Forces Institute of Pathology (AFIP) were studied by means of clinicopathologic correlation and histochemical, immunohistochemical, and ultrastructural methods to better define this entity. The cytoplasmic features of the balloon cells observed in BCMM resemble those noticed in balloon cell nevus (BCN), but the presence of nuclear pleomorphism, atypia, and mitoses and the absence of intervening stroma help distinguish BCMM. The cells also show many histochemical, immunochemical, and ultrastructural features of conventional melanoma cells. Although it is generally believed that balloon melanoma cells represent a degenerative change, the immunohistochemical and electron microscopic findings suggest that the balloon tumor cells are most likely metabolically active melanocytic cells. Microscopically, BCMM also must be differentiated from other clear cell tumors such as clear cell sarcoma (MM of soft parts), hibernoma, xanthoma, sebaceous neoplasms, metastatic renal cell carcinoma, (malignant) clear cell acrospiroma, (malignant) granular cell tumor, granular (clear) cell basal cell carcinoma, clear cell syringoma, and atypical fibroxanthoma. The prognosis of BCMM usually correlates with the tumor thickness similar to that in other histologic types of cutaneous MM. Nineteen (57.5%) of 33 patients with adequate follow-up information died of disseminated tumors from 2 months to 12 years after the initial treatment. Six (18.2%) patients developed local recurrences: four of these patients died of metastasis and two were alive with metastatic tumor at last contact. Five (15.2%) patients were alive with metastatic tumors, and seven (21.2%) were alive without evidence of disease at last contact. Recognition of BCMM is important because of its malignant biologic behavior.

Adult

Trichogerminoma. Report of 14 cases.

We report 14 cases of trichogerminoma, a rare form of cutaneous adnexal neoplasm, derived from hair germ epithelium. The neoplasms occurred in 9 men and 5 women. Their ages ranged from 16 to 73 years (median 53 years). The tumors were slow growing, asymptomatic dermal or subcutaneous nodules, located on the head and neck (6), trunk (4), extremities (2) and hip (1), with no distinguishing clinical features. Histologically, trichogerminomas were characterized by sharply circumscribed, pseudoencapsulated dermal and subcutaneous nodules, ranging in size from 0.4 to 4.0 cm in diameter (mean 1.9 cm). The nodules were subdivided into lobules separated by variable amounts of stroma that demonstrated varying cellularity and mucin content. The lobules were composed of basaloid cells that formed densely packed, round nests or "cell balls" resembling hair bulbs. The basaloid cells demonstrated peripheral palisading, keratinization and differentiation towards various pilosebaceous structures. Retraction spaces, well developed hair follicles and hair shafts were not observed. These distinctive histologic features separated these neoplasms from other tumors of pilar origin and from basal cell carcinoma. The trichogerminomas behaved in a benign fashion with one exception. Complete excision of the lesions is the treatment of choice.

Adolescent

Potent substituted-3 beta-phenyltropane analogs of cocaine have cocaine-like discriminative stimulus effects.

Two novel phenyltropane analogs of cocaine, 3 beta-(4-chlorophenyl) tropane-2 beta-carboxylic acid methyl ester (RTI-COC-31) and 3 beta-(4-methylphenyl) tropane-2 beta-carboxylic acid methyl ester (RTI-COC-32), were evaluated for cocaine-like discriminative stimulus effects in rats. Two groups of rats were trained to discriminate 10 mg/kg cocaine from saline using a standard 2-lever discrimination procedure with correct-lever responding reinforced under a fixed-ratio 20 schedule of food reinforcement. One group of rats was used to evaluate RTI-COC-31 and the unsubstituted-3 beta-phenyltropane reference compound WIN 35,065-2 in substitution tests. Another group of rats was used to evaluate RTI-COC-32. For purposes of comparison, a cocaine dose-effect curve was also determined in each group. Both RTI-COC-31 and RTI-COC-32, as well as WIN 35,065-2, substituted completely for cocaine. RTI-COC-31 was 26.8-fold and RTI-COC-32 was 6-fold more potent than cocaine for producing cocaine-lever responding. The potent cocaine-like effects of the RTI analogs in vivo correspond with their high affinities for a cocaine recognition site on the dopamine transporter, providing further evidence that this site may mediate behavioral effects of cocaine relevant to its abuse.

Animals

HMB-45 staining in benign and malignant melanocytic lesions. A reflection of cellular activation.

The antibody HMB-45 used as an immunohistochemical reagent has often been labeled as a marker for melanoma, even though some benign lesions have been noted to show positive staining reactions with this reagent. Biopsy specimens from 225 benign and malignant melanocytic lesions were examined after immunoperoxidase staining for S-100 protein and HMB-45. The lesions studied included common acquired nevi, spindle cell and epithelioid cell nevi (Spitz nevi), cellular blue nevi, deep penetrating nevi, congenital nevi, nevi from hormonally reactive areas (genital), malignant melanoma, and desmoplastic malignant melanoma. A positive reaction for HMB-45 was seen in the dermal component in a high percentage of each of these types of lesions except for the common acquired nevi and the desmoplastic malignant melanomas that were uniformly negative for HMB-45 in the dermal component. HMB-45 correlates with melanosome production and thus a melanocytic origin of HMB-45-positive cells. HMB-45 may correlate best with factors that stimulate melanocytic proliferation and production of melanosomes.

Adolescent

Majocchi's granuloma.

Majocchi's granuloma (nodular granulomatous perifolliculitis) is a well recognized but uncommon infection of dermal and subcutaneous tissue by fungal organisms (dermatophytes) usually limited to the superficial epidermis. The organism usually associated with Majocchi's granuloma is Trichophyton rubrum; however, other dermatophytes including T. mentagrophytes (variety granulosum), T. epilans, T. violaceum, M. audouinii, M. gypseum, M. ferrugineum, and M. canis may be the causative agent. A review of 17 cases revealed not only the variety of possible organisms but also a marked variation from the usual hyphal forms. The morphologic variations including yeast forms, bizarre hyphae, mucinous coatings, and the Splendore-Hoeppeli phenomenon may be factors which allow the dermatophytes to persist and grow in an abnormal location. Also, there is evidence that Majocchi's granuloma may occur in two distinct groups of patients.

Adult

Deep penetrating nevus.

We report a clinical and histologic study of 70 patients, each with a single melanocytic lesion termed "deep penetrating nevus" (DPN). The lesions are most commonly found on the face, upper trunk, or proximal extremities of patients between the ages of 10 and 30 years. Typically they are darkly pigmented. Histologically they are characterized by loosely organized nests of pleomorphic pigmented cells that penetrate deep into the reticular dermis and often to the subcutaneous fat. Follow-up was obtained from 48 patients. It ranged from 1 to 23 years (mean, 7 years). Despite an initial histologic diagnosis of malignant melanoma in 29% of the cases, there were no local recurrences and no distant metastases. It is important to differentiate DPN from malignant melanoma. The characteristic histologic features of DPN also allow its differentiation from spindle cell and epithelioid cell nevi and blue nevi.

Adolescent

Spindle cell and epithelioid cell nevi with atypia and metastasis (malignant Spitz nevus).

We report on the clinical and pathologic features of 32 lesions diagnosed as malignant spindle cell and epithelioid cell nevus (S&E nevus). Because of the clinical or initial histopathologic diagnosis of malignant melanoma, six patients had lymph node dissection. Three of these patients also had an enlarged lymph node. In all six cases, metastatic spindle or epithelioid cells were found in at least one of the resected lymph nodes. Of the 30 patients with follow-up information, including all six patients with lymph node metastases, all are alive and well. No recurrences or further metastases have been found. On histopathologic reevaluation, all the lesions had features of S&E nevi. Study of these cases suggests that although some lesions with features of S&E nevi may involve local lymph nodes, widespread metastases do not result.

Humans

Cutaneous myofibroma.

The clinical and pathologic features of an acquired skin tumor, which histologically is identical to infantile myofibromatosis, are presented. Thirty-four cases were studied, 26 of which were in patients over 14 yr of age. The median age was 36. None of the lesions was associated with recurrence after surgery, and metastases were not observed. Microscopically, the lesions were relatively well circumscribed and had a characteristic biphasic pattern which centrally showed features of vascular tumors, including hemangiopericytoma or glomus tumor. Ultrastructural examination identified cells with features of myofibroblasts, glomus cells, and pericytes. Immunoreactivity for muscle actin was strongly and diffusely positive in all tumors. The clinical significance of this entity lies primarily in its recognition as a distinctive benign neoplasm, most probably of vascular origin. The occurrence of this lesion is not limited to children; it may be an acquired lesion, and it may be found in the skin as well as soft tissue.

Adolescent

Behavioral effects of toxic doses of soman, an organophosphate cholinesterase inhibitor, in the rat: protection afforded by clonidine.

Atropine, a postsynaptic muscarinic antagonist, and clonidine, a presynaptic inhibitor of acetylcholine release, protect mice from the lethal effects of soman, a potent and irreversible cholinesterase inhibitor. The purpose of this study was to determine the effects of atropine (6 mg/kg) and clonidine (0.2 mg/kg) on soman-induced lethality and behavioral changes in the rat. Soman produced a dose-dependent increase in lethality over a narrow concentration range (50-200 micrograms/kg, SC). Soman produced time- and dose-dependent increases in tremor, salivation, hind limb extension, convulsions and chewing behaviors, as well as decreases in three normal stereotyped behaviors, sniffing, locomotion and rearing. Atropine and clonidine were equally effective at limiting soman-induced lethality and behavioral changes. The protective effects of clonidine and atropine were synergistic, even though clonidine antagonizes some of the stereotyped behaviors elicited by atropine. Simultaneous pretreatment with clonidine and atropine completely eliminated the lethality and behavioral changes produced by injection of 200 micrograms/kg soman.

Animals

Role of central biogenic amines on the protection afforded by clonidine against the toxicity of soman, an irreversible cholinesterase inhibitor.

Studies in our laboratory have demonstrated that alpha 2-adrenergic agonists such as clonidine offer protection against the toxicity caused by cholinesterase inhibitors such as soman. Experiments were designed to determine whether central catecholaminergic systems are implicated in the toxic and lethal manifestations of soman toxicity and whether the protection afforded by clonidine involves such pathways. Clonidine pretreatment resulted in a significant degree of protection from the lethal effects of soman in the mouse. Depletion of brain catecholamines did not alter soman-induced lethality or behavioral toxicity. Furthermore, catecholamine depletion was not effective in blocking clonidine-induced protection against soman toxicity. In contrast, elevation of brain catecholamines using the monoamine oxidase inhibitor, pargyline, resulted in significant protection against soman toxicity which was additive with that of clonidine.

Animals

Lycopodium granuloma.

The spores of Lycopodium (L) clavatum were used as a component of a dusting powder in many hospitals during the 1920's and 1930's. When L spores enter surgical wounds a lesion clinically resembling tuberculosis or neoplasia may develop months or even years later. We recently encountered a case of L granuloma occurring in a patient 50 years after an appendectomy. Three additional cases found in the files of the AFIP are also reported.

Aged

Primary cutaneous adenoid cystic carcinoma.

Primary adenoid cystic carcinoma of the skin is rare. Ten cases from the files of the Armed Forces Institute of Pathology were studied. Seven of the 10 cases recurred after initial surgery. The interval between surgery and recurrence ranged from 4 months to 20 years. In one case there was metastasis to lung and pleura. Histologically, cutaneous adenoid cystic carcinoma is indistinguishable from adenoid cystic carcinoma of the salivary gland. The diagnostic histologic features and the differentiation of adenoid cystic carcinoma from other cutaneous neoplasms are discussed.

Adult

Aggressive digital papillary adenoma and adenocarcinoma. A clinicopathological study of 57 patients, with histochemical, immunopathological, and ultrastructural observations.

Fifty-seven examples of a rare eccrine sweat gland tumor (aggressive digital papillary adenoma and adenocarcinoma) were studied by means of light microscopy, electron microscopy, and immunoperoxidase techniques. The neoplasm occurred as a single, painless mass, almost exclusively on the fingers, toes, and adjacent skin of the palms and soles. Microscopic features were distinct from those of other eccrine sweat gland tumors and often led to the diagnosis of such metastatic carcinoma as that of the breast. The characteristic histologic features included tubuloalveolar and ductal structures with areas of papillary projections protruding into cystic lumina. The stroma varied from thin, fibrous septae to areas of dense, hyalinized collagen. Forty tumors were classified as adenoma (ADPA) and 17 as adenocarcinoma (ADPAca). Histologically, ADPAca was distinguished from ADPA by its poor glandular differentiation and by necrosis, cellular atypia and pleomorphism, invasion of soft tissue and bone, and invasion of blood vessels. Eighteen (50%) patients with ADPA and 8 (47.0%) who had ADPAca developed recurrent lesions (2 months to 9 years) after surgical removal of the tumor. Seven (41.2%) patients with ADPAca developed metastases, of which 5 involved the lung. Three patients died of metastases, 5 to 20 years after surgical treatment of the primary tumor. The histologic malignant features in ADPAca are indicative of potential for distant metastasis and fatality. The recognition of aggressive digital papillary adenoma and adenocarcinoma as a distinct clinicopathological eccrine sweat gland neoplasm is important because of the potential for aggressive local growth and distant metastasis.

Adenocarcinoma, Papillary

Bowenoid papulosis. A clinicopathologic study with ultrastructural observations.

One hundred eight patients were studied who had anogenital lesions showing microscopic features as seen in bowenoid papulosis (BP), a recently described condition occurring most commonly in young adults. Patients typically show multiple papules, small nodules, or plaques that clinically mimic verrucae or nevocellular nevi. Although the lesions show microscopic cytologic atypia, a distinction from Bowen's disease, erythroplasia of Queyrat, and other forms of carcinoma in situ can usually be made on the basis of histologic and clinical criteria. The disorder responds to conservative treatment, although recurrences are not uncommon. Evolution of the lesions to invasive carcinoma was not observed. Mounting evidence links the development of BP to infection with human papilloma virus, but other viruses, as well as hormonal and immunologic factors, may also play a role.

Adolescent

Paget's disease of the ectopic breast with an underlying intraductal carcinoma: report of a case.

Paget's disease may occur at mammary and extramammary sites. Mammary Paget's disease typically involves the nipple and adjacent skin. Almost all such cases are associated with an underlying ductal carcinoma of the breast. A case of Paget's disease occurring at the site of an ectopic breast adjacent to a supernumerary nipple and associated with an underlying intraductal carcinoma is described. A search of the literature revealed no previous report of such cases. Detailed clinical history and histopathologic, histochemical, and follow-up information on this case are presented. The literature on mammary and extramammary Paget's disease is reviewed.

Biopsy

Cutaneous mercury granuloma. A clinicopathologic study and review of the literature.

Cutaneous mercury granulomas are rarely encountered. Clinically they pose difficulty in diagnosis when there is no clear history of penetrating injury by objects containing metallic mercury. Histologic, chemical, and scanning electron microscopic studies of such cutaneous lesions were performed on four cases from the Armed Forces Institute of Pathology files. Reported cases from the literature were reviewed. Metallic mercury in tissue sections appears as dark, opaque globules, usually spherical in shape and of varying sizes and numbers. A zone of collagen necrosis often surrounds the mercury globules. A granulomatous foreign body-giant cell reaction and a mixed inflammatory cellular infiltrate composed of neutrophils, lymphocytes, histiocytes, plasma cells, and occasional eosinophils are usually present. Epidermal and dermal necrosis, with or without ulceration or pseudoepitheliomatous hyperplasia, is also a common finding. The gold lysis test and energy-dispersive x-ray analysis confirmed the presence of metallic mercury in the tissue. Following cutaneous injury from mercury, systemic toxicity may develop and death may even occur. An approach to clinical management is discussed.

Adolescent